2059.     Intra-Voxel Incoherent Motion MRI in Rodent Model of Diethylnitrosamine-Induced Liver Fibrosis

Yue Zhang^1,2, Ning Jin^2,3, Jie Deng², Tamuna Chadashvili², Yang Guo², Guang-yu Yang⁴, Andrew Christian Larson^2,5

¹Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA; ²Department of Radiology, Northwestern University, Chicago, IL, USA; ³Department of  Biomedical Engineering, Northwestern University, Chicago, IL, USA; ⁴Department of Pathology, Northwestern University, Chicago, IL, USA; ⁵Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA

Intra-voxel incoherent motion (IVIM) imaging permits in vivo quantification of diffusion and perfusion. The purpose of our study was to investigate the relationship between hepatic IVIM measurements and diethylnitrosamine-induced fibrosis levels in the Wistar rat model.

                  2060.     Quantification of Hepatic Perfusion Fraction Using Diffusion-Weighted Imaging with Multiple B-Values: Utility for the Diagnosis of Liver Cirrhosis

Jignesh Patel¹, Eric Sigmund¹, Jens Jensen¹, Henry Rusinek¹, Marcel Oei¹, Bachir Taouli¹

¹NYU Medical Center, New York, NY, USA

In this study we have prospectively quantified advanced liver diffusion parameters including perfusion fraction, and diffusion coefficient using higher b-values (ADC High) in patients with liver cirrhosis and normal liver. Perfusion fraction was significantly lower in liver cirrhosis, demonstrating its potential utility for the diagnosis of cirrhosis.

                  2061.     Assessment of Vendor Dependency of Apparent Diffusion Coefficients – a Phantom Study at 1.5T

Sebastian Feuerlein¹, Axel Bornstedt², Arthur Wunderlich, Saed Boujraf², Volker Rasche²

¹Radiology, University of Ulm, Ulm, Germany, Germany; ²Internal Medicine II, University of Ulm, Ulm, Germany, Germany

The aim of this study was to compare the reproducibility and accuracy of ADC measurements on scanners from different vendors with comparable acquisition protocols.. Five plastic tubes (cyclohexane, butanol, destilled water, n-hexadecane, ethanol) were examined with a PROPELLER-DWI sequence (b-values 0,800) in 1.5T scanners of two different vendors. The resulting mean values were compared with the temperature-adjusted literature data. Although both vendors use different approaches for diffusion preparation, the reconstructed ADC value agreed excellently with the reported values in the literature. Vendor-independency can be seen as one important step toward clinical standards in DWI imaging.

                  2062.     Accuracy of Liver Tumour Apparent Diffusion Coefficients (ADC) Can Be Improved by Selecting Optimised B-Values

Matthew Blackledge¹, Matthew Orton¹, Dow-Mu Koh^1,2, Ben Wilton¹, Toni Wallace², Matin O. Leach¹, David J. Collins¹

¹CR UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK; ²Department of Radiology, Royal Marsden Hospital, Sutton, Surrey, UK

Optimal b-values for maximisation of liver tumour ADC accuracy and contrast are calculated based on a statistical evaluation of ADC data from studies investigating diffusion weighted imaging of hepatic disease. It is shown that b-values of 0 and 900 s mm^-2 should be used in a 1:3 ratio and evidence is given which supports these results.

                  2063.     SPIO Administration May Increase the Conspicuity of Malignant Liver Nodules on Diffusion Weighted Imaging

Karthik Ganesan¹, Masoud Shiehmorteza¹, Ana Almeida¹, Shay Heaton¹, Claude Sirlin¹

¹Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, CA, USA

DW imaging is considered one of the most sensitive techniques for detection of small (<=5mm) malignant nodules in the liver. However, some malignant liver nodules may have similar apparent diffusion coefficient (ADC) and T2 relaxation as liver and so may be difficult to detect on DW images. SPIO administration increases the ADC and also preferentially reduces the T2 of liver parenchyma. We hypothesize that administration of SPIO would increase the lesion to liver signal intensity on DW images by preferentially decreasing the T2 of liver relative to the malignant nodules and also by preferentially increasing the ADC of liver.

                  2064.     Removal of Olefinic Fat Signal in Body Diffusion-Weighted EPI Using a Dixon Method

Diego Hernando¹, Dimitrios C. Karampinos², Kevin F. King³, Justin Haldar¹, John G. Georgiadis², Zhi-Pei Liang¹

¹Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; ²Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; ³Applied Science Laboratory, General Electric Healthcare, Waukesha, WI, USA

The signal from olefinic fat protons in body DW-EPI is typically unaffected by chemical shift-based fat suppression methods, and introduces severe bias in the estimation of diffusion parameters. In this work, we propose a Dixon method for robust separation of water and olefinic fat signal. The proposed method uses magnitude images to avoid the phase distortions typical of DW-EPI. The method is demonstrated on phantom and in vivo datasets, and its performance is evaluated using Cramer-Rao bound analysis.

                  2065.     Diffusion-Weighted Imaging Using SS EPI of Abdominal Organs at 3T: Comparison with 1.5T

Andrew Rosenkrantz¹, Marcel Oei¹, Hersh Chandarana¹, Bachir Taouli¹

¹NYU Medical Center, New York, NY, USA

In this prospective study, we examined the reproducibility of ADC of abdominal organs between 1.5T and 3T. Three volunteers underwent DWI of the abdomen at both field strengths. There was no significant difference in ADC of the liver, kidney, pancreas, and spleen, although there was a trend toward lower liver ADC at 3T. Coefficient of variability of ADC between field strengths was moderate for all organs. DWI at 1.5T demonstrated less ghosting and significantly better subjective image quality scores. These findings were noted for two different sets of b-values. Given moderate CV, caution is warranted when ADC is compared between field strengths.

                  2066.     Q-Space Imaging of Abdominal Tumor

Andreas Lemke¹, Frederik Laun², Bram Stieltjes, Lothar Rudi Schad¹

¹Chair in Computer Assisted Clinical Medicine, University of Heidelberg, Faculty of Medicine, Mannheim, Germany; ²Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany

In this study, we demonstrate the first implementation of q-space imaging of the abdomen and evaluate its potential to improve the delineation of malignancies in comparison to conventional ADC-maps. We show that the implemented q-space sequence provides good image quality notwithstanding the abdominal motion. We also show that there is a substantial difference in signal decay between healthy pancreatic tissue and pancreatic tumor. In the resulting q-space derived maps, especially in the P(0) map, tumor delineation is clearly superior to conventional ADC maps

                  2067.     Effect of Number of Shots on the Calculated Apparent Diffusion Coefficient in Phantoms and in Human Liver in Diffusion Weighted Echo Planar Imaging

Masoud Shiehmorteza¹, Claude Sirlin¹, Tanya Wolfson², Anthony Gamst², Andre Soumekh¹, Shay Heaton¹, Chad Kohl³, Nicholas Pinto¹, Mark Bydder¹

¹Radiology, University of California San Diego, San Diego, CA, USA; ²Family and Preventive Medicine, University of California San Diego, San Diego, CA, USA; ³Radiology, University of Arizona

Purpose: To determine whether ADC measurement was influenced by number of shots in a diffusion-weighted single-shot SE EPI and to assess the magnitude of this effect for multiple b-value

                  2068.     Effects of Extracellular Hepatobilliary Gadolinium Based Contrast Agents on Apparent Diffusion Coefficient

Manuel Rodriguez^1,2, Masoud Shiehmorteza², Karthik Ganesan², Claude Sirlin²

¹Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; ²Radiology, Liver Imaging Group University of California San Diego, San Diego, CA, USA

The purpose of this study is to evaluate the effects of mixed extracellular hepatobilliary gadolinium based contrast agents (GBCA) on diffusion-weighted (Dw) imaging and apparent diffusion coefficient (ADC) values in patients with focal hepatic lesions. Twelve patients underwent Dw imaging and ADC values were acquired before and after the administration of mixed extracellular hepatobilliary GBCA. Our study showed that the administration of mixed extracellular hepatobilliary GBCA results in a mild but statistically significant elevation in hepatic ADC.

                  2069.     Improved Diagnostic Utility of T2-Weighted 3D-TSE Liver Imaging by Suppression of Vascular Signals Using a Motion-Sensitive Preparation

John P. Mugler, III¹, Wilhelm Horger², Berthold Kiefer²

¹Radiology, University of Virginia, Charlottesville, VA, USA; ²Siemens Healthcare, Erlangen, Germany

The purpose of this work was to evaluate the performance of a motion-sensitive preparation for suppressing the signal from vascular structures in T2-weighted 3D turbo-spin-echo (TSE) images of the liver. We found that the addition of a motion-sensitive preparation based on adiabatic RF pulses was effective for suppressing the signal from small vascular structures, thus eliminating potential ambiguity between vascular structures and small liver lesions. We anticipate that this improvement will enhance the diagnostic utility of single-slab, 3D-TSE imaging of the liver.

                  2070.     Respiratory-Navigated Free Breathing 3D-SPGR Sequence for Contrast-Enhanced Examination of the Liver:  Diagnostic Utility and Comparison with Free Breathing and Breath-Hold Conventional Exams.

Phillip Young¹, Anja Brau², Yuji Iwadate³, Shreyas Vasanawala¹, Bruce Daniel¹, Robert Herfkens¹

¹Radiology, Stanford University, Palo Alto, CA, USA; ²Applied Science Laboratory West, GE Healthcare, Menlo Park, CA, USA; ³Applied Science Laboratory Japan, GE Healthcare, Tokyo, Japan

We present our initial experience with a respiratory-navigated 3D SPGR sequence with 2-point Dixon water-fat separation for liver imaging in 14 patients. After conventional liver imaging, a respiratory triggered exam was performed and compared to breath-held and free breathing non-navigated images with otherwise identical parameters. While inferior to breath-held images, the navigated images showed a modest but statistically significant improvement over free breathing images. This method may provide an option for imaging patients with limited or no breath holding ability, and further investigation of the use of this sequence in such patients is indicated.

                  2071.     Evaluation of the Relationship Between Respiratory Hepatic and Renal Motion Using Real-Time MRI

Aaryani Tipirneni^1,2, Ruitian Song¹, Ralf B. Loeffler¹, Claudia M. Hillenbrand¹

¹Radiological Sciences, St Jude Children's Research Hospital, Memphis, TN, USA; ²Biomedical Engineering, University of Memphis, Memphis, TN, USA

For navigated slice tracking of a specific organ an appropriate tracking factor TF describing the motion of the organ with respect to the superior-inferior diaphragm movement needs to be applied. Information about TF may improve the image quality, increase the window size, and reduce the total scan time. The effectiveness of the navigator approach can, however, be degraded by erroneous TF values. Hence, we investigate renal TFs in 3 directions (superior inferior, anterior-posterior, and medial-lateral) with respect to the liver/diaphragm motion. We present mean TF data derived from organ motion measurements in eight healthy volunteers.

                  2072.     Quantitative Multi-Dimensional PROPELLER MRI of Diethylnitrosamine-Induced Hepatocarcinogenesis in Wistar Rat Model

Jie Deng^1,2, Ning Jin¹, Guang-yu Yang³, Reed A. Omary^1,4, Andrew C. Larson^1,4

¹Department of Radiology, Northwestern University, Chicago, IL, USA; ²Department of Medical Imaging, Children's Memorial Hospital, Chicago, IL, USA; ³Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; ⁴Robert H. Lurie Comprehensive Cancer Center , Northwestern University, Chicago, IL, USA

Development of hepatocellular carcinoma (HCC) involves a multi-step carcinogenesis beginning with a benign regenerative nodule, progressing to a premalignant dysplastic nodule and overt HCC. Multi-dimensional quantitative MRI combining T2, M0 and ADC measurements can provide increased parameterization for accurate tumor tissue characterization. However, implementation of multi-dimensional quantitative methods for abdominal tumors is challenging. A combined PROPELLER acquisition approach providing both T2 and diffusion-weighted (DW) measurements could provide inherently co-registered functional maps. The purpose of this study was to evaluate a quantitative multi-dimensional PROPELLER MRI approach for the characterization of the hepatic nodules during hepatocarcinogenesis in the diethylnitrosamine rat model.

                  2073.     Liver MR Image Quality: Reducing Anisotropic Noise in Zero-Filled Spin-Warp Imaging

Gregory J. Wilson^1,2, Jeffrey H. Maki^2,3

¹MR Clinical Science, Philips Healthcare, Cleveland, OH, USA; ²Radiology, University of Washington, Seattle, WA, USA; ³Radiology, Puget Sound VAHCS, Seattle, WA, USA

Recent improvements in dynamic contrast enhanced (DCE) liver imaging have lead to more refined scrutiny of image quality. A subtle artifact in signal-to-noise (SNR)-limited liver MR is the appearance of a “cross-hatch” noise pattern in spin-warp images. This study explores a possible source of this noise pattern. Simulations show the combination of spin-warp imaging (acquiring the corners of k-space) and zero-filled reconstruction produce the anisotropic noise pattern in standard reconstructions. Two isotropic reconstruction filters are implemented to reduce anisotropic noise in liver MR while attempting to maintain SNR and resolution. The filters effectively reduce the appearance of anisotropic noise in liver MR.

                  2074.     The Hepatic Uptake of Gd-EOB-DTPA Is Strongly Affected by the Hepatobiliary Function

Olof Dahlqvist Leinhard^1,2, Nils Dahlström^1,2, Per Sandström³, Anna Freij⁴, Johan Kihlberg², Torkel Brismar⁵, Örjan Smedby^1,2, Peter Lundberg^1,2

¹Department of Medical and Health sciences, Linköping University, Linköping, Sweden; ²Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; ³Department of Surgery, Linköping University, Linköping, Sweden; ⁴Radiation Physics, Linköping University Hospital, Linköping, Sweden; ⁵Karolinska University Hospital, Stockholm, Sweden

The late hepatic uptake of Gd-EOB-DTPA was quantified in 10 healthy subjects and 21 patients with suspected hepatobiliary disease. A strong reduction in contrast concentration in the liver was observed in late phases in patients with impaired hepatobiliary function. The uptake also showed a strong correlation with clinical liver status scores (MELD and Child-Pugh). The results indicate that it is possible to assess hepatobiliary function within a clinical MRI protocol by measuring hepatic uptake of Gd-EOB-DTPA.

                  2075.     Estimation of Fatty Liver with T2* Correction Using 2D Multiecho-FFE: Human Study Before and After SPIO or Gd-EOB-DTPA Administration

Kengo Yoshimitsu¹, Hiroshi Honda², Shutaro Saiki³, Tomoyuki Okuaki³, Marc Van Cauteren³

¹Radiology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; ²Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; ³Philips Medical Systems, Japan

Newly developed mFFE sequence can provide consistent fat fraction regardless of T2* or T1 alteration of the liver tissue, as compared to conventional duel-echo FFE. This may be applicable to evaluation of the fatty liver in CHC or NASH patients, or even for patients after SPIO or Gd-EOB-DTPA administration.

                  2076.     High-Resolution Free-Breathing 3D T1 Weighted Hepatobiliary Imaging Optimized for Gd-EOB-DTPA

Scott K. Nagle¹, Reed F. Busse², Anja C.S. Brau³, Jean H. Brittain², Yuji Iwadate⁴, Sina Meisamy¹, Yu Grace Zeng¹, Scott B. Reeder^1,5

¹Radiology, University of Wisconsin, Madison, WI, USA; ²Applied Science Laboratory, GE Healthcare, Madison, WI, USA; ³Applied Science Laboratory, GE Healthcare, Menlo Park, CA, USA; ⁴Applied Science Lab, GE Healthcare, Hino, Japan; ⁵Medical Physics, University of Wisconsin, Madison, WI, USA

Conventional contrast-enhanced delayed hepatobiliary imaging has used breath-hold acquisitions, which inherently limits spatial resolution and

                  2077.     Improved Contrast Enhancement of Experimentally Induced Rat Hepatocellular Carcinoma Using New Blood Pool Contrast Agent Dendrimers DTPA-D1Glc(OH)

Yasuo Takehara¹, Takashi Aoki², Mitsuji Yamashita², Michio Fujie³, Katsuaki Muramatsu³, Harumi Sakahara³, Norihiro Sadato⁴, Hiroyasu Takeda³

¹Radiology, Hamamatsu University Hospital, Hamamatsu, Shizuoka, Japan; ²Shizuoka University Graduate School of Technology; ³Hamamatsu University School of Medicine; ⁴National Institute for Physiological Science

Newly developed blood pool agent can provide improved and sustained contrast enhancement of experimentally induced rat hypervascular hepatocellular carcinoma with lower dosage of 1/8 of Gd-DTPA at molecular basis.

                  2078.     Functional Liver Imaging Using Partial Least Squares (PLS) Analysis

Alyaa Hussein Elzibak^1,2, Jeff Fortuna^2,3, John F. MacGregor³, Colm Boylan⁴, Michael D. Noseworthy^2,5

¹Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada; ²Brain-Body Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada; ³Chemical Engineering, McMaster University, Hamilton, Ontario, Canada; ⁴Diagnostic Imaging, St. Joseph's Healthcare, Hamilton, Ontario, Canada; ⁵Electrical and Computer Engineering, School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada

We developed a liver challenge procedure that relies on modulating the BOLD signal with hyperoxia and meal intake. Temporal BOLD data analysis using partial least squares (PLS) was superior to a traditional general linear model (GLM). We show how the method can differentiate healthy from diseased liver tissue.

                  2079.     Stimulatory Effect of Glucokinase Activation on Hepatic Glycogen Turnover as Measured by 13C-MRS

Didier Laurent¹, Brittany Yerby¹, Jiaping Gao¹, Alokesh Duttaroy¹

¹Novartis Institutes for Biomedical Research, Cambridge, MA, USA

A primary defect in hepatic glucose uptake may lead to an excessive rise in plasma glucose following meal ingestion. In response to rising levels of plasma glucose, glucokinase (GK) activation causes a shift in glucose metabolism towards storage and utilization. Here, we used 13C-MRS to measure, in a rat model of insulin resistance, the effects of a GK activator on hepatic G6P and glycogen contents. We demonstrate that GK activation is followed by a drastic increase in both glycogen synthesis and breakdown, suggesting that hepatic glycogen metabolism can be used as an early biomarker of drug efficacy.

                  2080.     MR Elastography: Spleen Stiffness Measurements in Healthy Volunteers.

Lorenzo Mannelli¹, Ilse Joubert¹, Martin Graves¹, Andrew Patterson¹, Richard Black², David J. Lomas¹

¹Radiology, Addenbrooke's Hospital and University of Cambridge, Cambridge, UK; ²Medical Physics, Addenbrooke's Hospital and University of Cambridge, Cambridge, UK

Splenic stiffness has been proposed as a potential new marker of portal hypertension. This requires that a normal range can be established. MR Elastography of the spleen using two different driver locations was performed in 16 healthy volunteers and correlated with age, body mass index, spleen volume, blood pressure and liver stiffness. There were no significant correlations observed but the results varied slightly by driver location: right anterior 3.6 ± 0.59 kPa; left anterior 4.3 ± 0.63 kPa. The overall results suggest that using a consistent technique splenic MRE warrants further investigation as a non-invasive marker of portal hypertension.

                  2081.     Cross-Validation of Magnetic Resonance Elastography and Ultrasound-Based Transient Elastography in Phantom Materials

Jun Chen¹, Jennifer Oudry², Kevin Glaser¹, Véronique Miette², Laurent Sandrin², Richard Ehman¹

¹Mayo Clinic, Rochester, MN, USA; ²Echosens, Paris, France

Currently Magnetic resonance Elastography (MRE) and Ultrasound-based Transient Elastography (UTE) have shown usefulness for diagnosing hepatic fibrosis. Comparisons between them has been done in-vivo, but lacked the control necessary to assess the agreement of the fundamental mechanical properties measured by the two techniques. This study directly compared the stiffness values measured by MRE and UTE on a set of well-characterized phantoms, demonstrated excellent correlation in measurement of shear stiffness, and no evidence of systemic differences.

                  2082.     Molecular MRI of Liver Fibrosis

Peter Caravan¹, Ritika Uppal¹, Bryan Fuchs², Alexander Guimaraes¹, George Dai¹, Tsutomo Fujii², Kenneth Tanabe²

¹Radiology, Massachusetts General Hospital, Charlestown, MA, USA; ²Surgery, Massachusetts General Hospital, Boston, MA, USA

Liver fibrosis occurs in advanced stages of chronic liver diseases, and proper staging of fibrosis is essential for prognosis, surveillance, and treatment decisions. Fibrosis is characterized by excess deposition of type I collagen in the parenchyma. We used a rat model of liver fibrosis and imaged fibrotic and control animals before and after administration of a type I collagen-targeted Gd-based contrast agent. Significant signal enhancement was observed in the fibrotic animals compared to the controls and this correlated with quantitative measures of total liver collagen and histological staining for fibrosis.

                  2083.     Ex-Vivo MR Imaging of Excised Human Livers as a New Method to Reliably Co-Localize Nodules and Nodule Components on Imaging and Pathology: Preliminary 6-Month Experience

Karthik Ganesan¹, Emil Achmad¹, Irene Mwangi², Chad Kohl², Shalini Ananda², Ana Almeida², Manuel Rodriguez³, Michael Peterson⁴, Claude Sirlin²

¹Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, CA, USA; ²Liver Imaging Group, Department of Radiology, University of California San Diego, USA; ³Liver Imaging Group, Department of Radiology, University of Southern California, Los Angeles, USA; ⁴Department of Pathology, University of California San Diego, USA

MR imaging is used to detect, stage, and characterize liver nodules. However, MR is insensitive to small nodules and relatively unable to predict histological tumor grade. One obstacle to progress in the field is that presently there is no reliable method to spatially co-localize nodules and nodule components at MR imaging and at pathology. We have implemented a system in which liver specimens are imaged ex-vivo prior to pathology sectioning. This system permits accurate image-guided tissue sampling and reliable radio-pathological correlation of small nodules and nodule components. This abstract describes our co-localization technique and our preliminary six-month experience

                  2084.     MR Manifestations of Ovarian Clear Cell Adenocarcinomas: A Pictorial Review

Kenji Matsuzaki¹, Mayumi Takeuchi¹, Hiromu Nishitani¹

¹Department of Radiology, University of Tokushima, Tokushima, Japan

MR manifestations of ovarian clear cell adenocarcinomas were reviewed. Unilocular large cystic mass containing serous or hemorrhagic fluid with contrast-enhanced mural nodules, which show very high intensity on DWI with low ADC (1.10 +/- 0.21, n=10), is the typical finding. Various histologic subtypes may be admixed in a tumor and not correlate with imaging features. Clear cell adenocarcinoma may arise from endometriosis in relatively younger women, and prognosis is poor in the advanced stage disease. To detect mural nodules is important for the early diagnosis, and subtraction imaging is helpful to evaluate small nodules in hyperintense cyst on T1WI.

                  2085.     Detection of Pelvic Lymph Nodes: Diffusion Weighted Imaging Increases Lymph Node Detection Rate When Added to Conventional MRI.

Wenche Margrethe Klerkx¹, Willem Mali, Gerard de Kort, Peter Heintz, Taro Takahara, Daisy Sie-Go, Petra Peeters

¹University Medical Center Utrecht, Utrecht, Netherlands

Heavily diffusion weighted images with fat suppression result in high contrast-to-noise ratios in which lymph nodes (both malignant and benign) are highlighted. In our study this led to an 14% improved the detection rate of pelvic lymph nodes. Lymph nodes detected by DWI in addition to conventional MRI were on average significantly smaller than those detected by conventional MR. We hypothesize that sensitivity of MR imaging in nodal staging could further increase if DWI is able to localise more lymph nodes; and subsequently evaluate these nodes by the apparent diffusion coefficient.

                  2086.     Pseudo 3D DWI of the Female Pelvis: A Potential Means of Increasing Staging Accuracy

Martin D. Pickles¹, Lindsay W. Turnbull¹

¹Centre for MR Investigations, University of Hull, Hull, East Yorkshire, UK

DWI is increasingly used to stage gynaecological malignancies. Traditionally to acquire DWI a 2D approach has been implemented. To fully assess the uterus and cervix DWI acquired in the sagittal plane and perpendicular to the long axis of the uterus/cervix would be advantageous. Obviously, these additional sequences would lead to an increased total scan time. In this work we describe the acquisition of a ‘3D’ DWI sequence that not only provide a means of reformatting DWI in any desired plane but also facilitate registration/fusion with other imaging while maintaining an acceptable imaging time.

                  2087.     Limitations of 3D T2 SPACE for Evaluation of the Female Pelvis at 3.0T

Elizabeth Hecht¹, Silaja Yitta¹, Ruth Lim¹, Erin Fitzgerald¹, Pippa Storey¹, Kamil Banibaker¹, Genevieve Bennett¹

¹New York University, New York, NY, USA

A 3D technique with high spatial resolution and multiplanar reconstruction is advantageous for imaging female anatomy and could reduce overall scan time, by eliminating multiple/repeat scans. A 3D T2 TSE sequence with RESTORE pulse and variable flip angle offers the promise of high resolution volumetric T2 imaging with low blurring and SAR which is useful at high field. However, there are pitfalls including increased susceptibility to B1 homogeneity and brightness of fat signal limiting fat/water distinction. The purpose of this study is to compare a 3D SPACE sequence with 3-plane 2D TSE for imaging of the female pelvis at 3T.

                  2088.     Parallel RF Transmission at 3.0T High-Field MRI:  Preliminary Results of High Spatial Resolution Pelvic MRI

Jürgen Gieseke¹, Winfried A. Willinek², Roy König², Marco Nijenhuis³, Guido Kukuk², Romhild Hoogeveen³, Barbara Brecher², Magnus Andersson², Eugen Muschler², Andreas Müller², Petra Mürtz², Frank Träber², Wolfgang Block², Daniel Thomas², Christiane K. Kuhl², Hans H. Schild², Nuschin Morakkabati-Spitz²

¹Clin. Science, Philips Healthcare, Senden, Germany, Germany; ²Department of Radiology, University of Bonn, Germany; ³Philips Healthcare, Netherlands

Parallel RF transmission holds the promise of reducing dielectric resonance effects at high field strengths and enables control of RF distribution to optimize RF deposition. To our knowledge, it is for the first time that these techniques are available on high-field MR systems used in clinical routine. Our study demonstrates that parallel RF transmission in MR imaging of the pelvic region enables to maintain the high diagnostic image quality of standard single transmission sequences while offering the potential to significantly reduce scan time.

                  2089.     Vascular Bed Volume Change of Uterine Fibroids After GnRHa Treatment: Assessment with Gadolinium-Enhanced Dynamic R2* Imaging

Shigeo Okuda¹, Koichi Oshio¹, Akihiro Tanimoto¹, Hironori Asada², Masahiro Jinzaki¹, Ayano Akita¹, Hirotaka Akita¹, Tomonori Hada³, Masataka Furuya⁴, Hiroshi Shinmoto⁵, Yasunori Yoshimura⁴, Sachio Kuribayashi¹

¹Department of Diagnostic Radiology, Keio University School of Medicine, Shinjyuku-ku, Tokyo, Japan; ²Department of Obstetrics and Gynecology, Keio University School of Medicine, TokyoTokyo, Japan; ³Department of Obstetrics and Gynecology, Keio University School of Medicine, Japan; ⁴Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan; ⁵Department of Radiology, National Defense Medical College, Saitama, Japan

The purpose of our study is to assess vascular bed volume change of uterine fibroids after GnRHa treatment by using Gadolinium-enhanced dynamic R2* imaging (R2*I). Double-echo fast SPGR sequence was utilized to generate R2*I. A total of 25 patients was assessed with R2*I before and after the treatment. We measured area-under-the-curve (AUC) of signal intensity curve in selected ROI (3x3 cm) on R2*I, and compared AUCs of the first and second examinations. Although increase of AUC value was observed in four patients, the mean values of AUC were decreased from 40.2 to 19.0 with significant difference (p<.0001, paired t test).

                  2090.     Signal Intensity Changes During Physiological Movement: Comparison of Uterine Myometrium and Myocardium

Tetsuro Araki¹, Izumi Imaoka¹, Kazuhiko Nishimatsu¹, Masatomo Kuwabara¹, Yukinobu Yagyu¹, Masahiro Okada¹, Taro Shimono¹, Seishi Kumano¹, Ryuichiro Ashikaga¹, Takamichi Murakami¹

¹Radiology, Kinki Univ., Osaka-Sayama, Japan

The purpose of this study was to compare uterine myometrium and myocardium on cine MR imaging with wall thickness and signal intensity (SI) measurement.

                  2091.     Measuring Blood Movement in the Placenta Using IVIM at 1.5 T

Ali Mohammad Al-Radaideh¹, Vian Kareem¹, Carolyn Costigan², Nia Jones, Tomas Paus³, George Bugg, Penny A. Gowland¹

¹Sir Peter Mansfield Magnetic Resonance Centre, The University Of Nottingham, Nottingham, UK; ²Brain and Body Centre, The University Of Nottingham, Nottingham, UK; ³Brain and Body Centre, The University of Nottingham, Nottingham, UK

DTI can used to measure IVIM parameters related to placental blood movement at 1.5 T. Previous placental IVIM data acquired at 0.5 T only provided sufficient SNR to map f, but the at 1.5 T sufficient SNR is available to obtain useful information from D* and D. Intrasubject repeatability is good. Data are presented for a range of gestational ages.

                  2092.     DCE-MRI Temporal Resolution Requirements for Vascular Permeability Measurements in Rhesus Macaque Reproductive Tissues

Ian J. Tagge¹, Cecily V. Bishop², Richard L. Stouffer^2,3, Charles S. Springer, Jr. ¹, Xin Li¹

¹Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA; ²Division of Reproductive Sciences, ONPRC, Oregon Health & Science University, Portland, OR, USA; ³Department of Obstetrics and Gynecology, Oregon Health & Science University

The female reproductive uterus and ovary are among the few normal tissues to undergo periodic changes in angiogenesis. Using a primate model (rhesus macaque) we investigated the effects of temporal resolution on the precision and accuracy of K^trans determination with the second-generation three-site water exchange DCE-MRI model.

                  2093.     MR Quantification of Abnormal Stromal Enhancement in the Periphery of Invasive Breast Tumors

Nima Nabavizadeh^1,2, Catherine Klifa¹, David Newitt¹, Ying Lu¹, Jona Hattangadi³, Clark Fisher², Nola Hylton¹, Catherine Park²

¹Radiology, University of California, San Francisco, San Francisco, CA, USA; ²Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; ³Radiation Oncology, Harvard Medical School, Boston, MA, USA

In this study, we hypothesized that abnormalities in vasculature exist within the histologically normal appearing periphery of breast tumors that can be detected by measuring changes in MR enhancement intensity. Using breast tissue proximity maps and percent enhancement values obtained from dynamic contrast-enhanced MRIs, we found that the normal breast stroma within 0 to 2cm of a primary tumor exhibits higher enhancement levels than stroma located far from the tumor region. These results suggest that tissue surrounding the tumor region may contain vasculature abnormalities or tumor-related angiogenesis, which could potentially help refine surgery and radiation therapy for breast cancer.

                  2094.     Comparison of Fibroglandular Tissue Density Evaluated by MRI in Three Different Racial Groups

Hoanglong Nguyen¹, Ke Nie¹, Jeon-Hor Chen^1,2, Chieh-Chih Hsu², Daniel Chang¹, Sandy Shih², Doris Hsu², Byron Feig¹, Dustin Newell¹, Hon J. Yu¹, Orhan Nalcioglu¹, Min-Ying Lydia Su¹

¹Tu & Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, USA; ²Department of Radiology, China Medical University, Taiwan

We measured the breast volume, fibroglandular tissue volume, and the percent density in 321 women from 3 racial background (Caucasians, Hispanics, and Asians). The age and race-dependence of breast density was analyzed using logistic regression models controlling for multiple variables. The fibroglandular tissue volume and the percent density showed a strong age-dependence. The Asian women had higher percent density compared to the White and Hispanic women, but the differences were found to come from the smaller breast volume in the Asians containing comparable fibroglandular tissue volume. Our findings were consistent with results analyzed using mammography from a large subject cohort.

                  2095.     Assessment of Four Different DWI Pulse Sequences Used for Breast Imaging

Martin D. Pickles¹, Peter Gibbs¹, Julie Pounder¹, Lindsay W. Turnbull¹

¹Centre for MR Investigations, University of Hull, Hull, East Yorkshire, UK

DWI of the breast can be problematic since a large FOV is required over non-uniform tissue which includes a large amounts of air. A variety of different pulse sequences are available. In this work we investigate which of four diffusion schemes is best suited to breast DWI by undertaking both phantom and in vivo SNR and GSR tests in conjunction with qualitative assessment of in vivo image quality. The results of this study identified that in those schemes that utilise an IR pulse to null the fat signal a statistically significantly superior image quality was noted.

                  2096.     Variation of the Apparent Diffusion Coefficient Measured from Various Regions of the Normal Breast Tissue Using Diffusion Weighted MRI as a Function of Various Phases of the Menstrual Cycle.

Rani Gupta Sah¹, Uma Sharma¹, Rajinder Parshad², Naranamangalam R. Jagannathan¹

¹Department of NMR and MRI Facility, All India Institute of Medcial Sciences, New Delhi, Delhi, India; ²Department of Sugical Disciplines, All India Institute of Medcial Sciences, New Delhi, Delhi, India

ADC calculated using Diffusion weighted MRI from various regions of normal breast of 9 volunteers revealed cyclic variation in ADC of para-areolar region during various phases of menstrual cycle. In para-areolar region, ADC was 1.9 ± 0.01 during proliferative phase and reduced to 1.73 ± 0.03 and 1.70 ± 0.04 during follicular and luteal phases. It increased to 1.91 ± 0.16 and 1.98 ± 0.15 during secretory and menstrual phases. No change was observed for upper, lower and central quadrants. Assessment of breast disease using ADC needs careful consideration of location and effect of menstrual related variation in tissue characteristics.

                  2097.     The Effect of B1 Inhomogeneity on Enhancement Ratio Measurements Using DCE-MRI of the Breast at 3T.

C A. Azlan^1,2, Trevor S. Ahearn¹, Gordon D. Waiter¹, Scott I. Semple³, Fiona J. Gilbert¹, Thomas W. Redpath¹

¹Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Scotland, UK; ²Department of Biomedical Imaging, University of Malaya, Kuala Lumpur, Malaysia; ³Department of Medical Physics, University of Edinburgh, Edinburgh, Scotland, UK

B1 inhomogeneity is a major drawback of 3T MRI and may affect the accuracy of enhancement ratio (ER) measurement after DCE-MRI of the breast. To simulate the effect of B1 inhomogeneity on DCE-MRI, T1-weighted FLASH images of gel phantoms were acquired using a range of flip angles. We show that there is an underestimation of ER, which increases with ER, as B1 decreases. Clinically 100% enhancement is frequently used as a threshold for malignancy. At this level we show that for a 54% B1 field there is a 20% underestimation of ER. This underestimation could reduce the specificity/sensitivity of DCE-MRI of the breast.

                  2098.     High-Resolution, Fat-Suppressed, Diffusion-Weighted MRI of the Breast Using a Self-Navigated Multi-Shot Technique

Wouter B. Veldhuis¹, Chunlei Liu¹, Roland Bammer¹, Bruce L. Daniel¹, Michael E. Moseley¹

¹Dept of Radiology / Lucas MRI Center, Stanford University, Palo Alto, CA, USA

With increasing resolution the readout time for conventional single-shot diffusion-weighted echo-planar imaging (DW-EPI) lengthens to the point that blurring and geometric distortions impair image acquisition. Here we compare high-resolution 256x256 multi-shot breast-DW MRI using SNAILS, to DW-EPI with parallel imaging. Free-breathing, axial, bilateral DW-data sets were acquired in 6 healthy volunteers at 1.5T. SNAILS allowed distortion free acquisition of 256² data sets, not possible with DW-EPI, even with parallel imaging. Comparison of apparent diffusion coefficient (ADC) values at 128² resolution, showed that ADCs obtained with DW-EPI are lower than those obtained with SNAILS, with identical b-value combinations.

                  2099.     Benign-Malignant Lesion Differentiation Using Functional ADC-Thresholding – Allowing Expert Radiologist Interpretation – Versus Conventional Thresholding Based on ADC Cut-Off Values

Wouter B. Veldhuis¹, Chunlei Liu¹, Yung Do¹, Thomas J. Brosnan¹, Michael E. Moseley¹, Bruce L. Daniel¹

¹Dept of Radiology / Lucas MRI Center, Stanford University, Palo Alto, CA, USA

Diffusion-weighted imaging (DWI) may aid in the discrimination of benign from malignant (breast) lesions. Approaches to benefit from the information contained in the DWI dataset have mostly been based on trying to define a cut-off value for the lesion ADC. This abstract compares the application of a new “functionally-thesholded” apparent diffusion coefficient (ftADC)-mapping algorithm to conventional ADC-thresholding by analyzing the diagnostic accuracy of both methods using a data set of 65 pathology-proven breast-MRI lesions. Using receiver-operating-characteristics (ROC)-curves it is shown that lower ADC correlates with a higher chance of malignancy and that ftADC-mapping improves diagnostic accuracy over conventional ADC thresholding.

                  2100.     Diagnostic Accuracy of High-Resolution Multi-Shot Diffusion-Weighted MRI for the Detection of Breast Cancer

Wouter B. Veldhuis¹, Chunlei Liu¹, Yung Do¹, Michael E. Moseley¹, Bruce L. Daniel¹

¹Dept of Radiology / Lucas MRI Center, Stanford University, Palo Alto, CA, USA

The diagnostic accuracy of multi-shot high-resolution, 256x256, diffusion-weighted (DW) MRI for the detection of breast cancer was determined in a retrospective analysis of 103 consecutive women undergoing MRI at 1.5T. DW-MRI was compared to dynamic-contrast-enhanced (DCE) sequences and to pathology and to a new approach of presenting DW-derived information in a “functionally-thresholded” (ft)-ADC map”. It is shown that high-resolution DWI increases specificity over DCE-MRI from 45% to 81% and that ftADC-mapping further increases specificity to 93%. It is concluded that a contrast-free MRI-protocol, that includes DW imaging, may have a clinically acceptable diagnostic performance.

                  2101.     The Optimized B Value of Breast Diffusion Weighted MRI

JING ZHANG¹, LIU QUAN CHENG¹, YONG GUO², FEI SUN³

¹Radiology, PLA General Hospital, Beijing, China; ²Radiology, Navy General Hospital, Beijing, China; ³GE Healthcare, China

DWI has been reported to have the potential of differentiation between malignant and benign breast tumor. To optimize the b value, we compared the ADC values of benign tumors with malignant tumors using DWI with different b values (range from 0 to 2600 s/mm2) in the same patient. When b value was in the range of 600 ~ 1200 s/mm2, the ADC of malignant tumor stayed relatively invariable and was statistically different with benign tumor. For good image quality and valid differentiation between malignant and benign tumor, the optimized b value is in the range of 600~1200 s/mm2.

                  2102.     Identification of Breast Calcification Using MRI

Ali Fatemi-Ardekani^1,2, Michael D. Noseworthy^2,3, Colm Boylan⁴

¹Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada; ²Brain-Body Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada; ³Electrical and Computer Engineering, School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada; ⁴Diagnostic Imaging, St. Joseph's Healthcare, Hamilton, Ontario, Canada

Susceptibility Weighted Imaging (SWI) shows exquisite structural details with unprecedented resolution. This technique is of significant interest for breast imaging, especially in detecting micro-calcification. Calcification, an early indicator of ductal carcinoma in situ, an invasive form of breast cancer, is not clearly visible on either conventional MR images or X-ray mammography of dense breast tissue. Here we show how optimized SWI detects calcification with an over estimation of lesion volume by a factor of 2, yet with better contrast than CT.

                  2103.     In Vitro MRI Identification and Characterization of Small Calcium Crystals: Implications for Breast Cancer

Devkumar Mustafi¹, Elizabeth Peng¹, Jeremy Palgen¹, Jonathan River², Sean Foxley², Gregory S. Karczmar²

¹Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA; ²Radiology, The University of Chicago, Chicago, IL, USA

We tested several MRI methods for the identification and characterization of small calcium crystals for probing microcalcifications in breast cancer. High-resolution MR images were acquired of small crystals imbedded in air bubble-free agar phantoms. True sizes of crystals, their amplifications and the variations in magnetic susceptibility between agar and Ca-crystals were precisely determined. Spin echo images accurately depicted the true size of the calcifications. Although gradient echo images significantly amplified crystal sizes due to blooming artifacts, images were distorted. Calcifications were amplified and easily seen in water peak height images derived from high resolution echo planar spectroscopic imaging data.

                  2104.     World of Phantoms: Reference Standards for Bench to Breast MRI

Devkumar Mustafi¹, Elizabeth Peng¹, Marieke Heisen², Abbie M. Wood³, Johannes Buurman⁴, Gregory S. Karczmar³

¹Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA; ²Biomedical Image Analysis, Eindhoven University of Technology, Eindhoven, Netherlands; ³Radiology, The University of Chicago, Chicago, IL, USA; ⁴Healthcare Informatics, Philips Healthcare, Netherlands

We have developed a method for making air bubble-free agar phantoms for MRI that mimic human tissue in terms of their relaxation pathways and other magnetic interactions. Here, we describe phantoms designed for two different applications: (1) phantoms with varying concentrations of agar and Omniscan that are used for periodic quality assurance to evaluate overall scanner function; and (2) a unique soft phantom designed for attachment to the breast that can be scanned in the course of each clinical protocol. Fat was suspended in an irregular pattern so that the phantom more accurately simulated breast tissue.

                  2105.     Three Images from Two Echoes: Reconstruction of Water, Fat and Silicone Images Using a Combined One-Point and Two-Point Dixon Approach. Application to  3D GRE in Breast Implant Imaging.

Christian Geppert¹, Valdimir Jellus¹, Berthold Kiefer¹

¹Siemens Healthcare, Erlangen, Germany

A novel method is proposed that combines single and two point Dixon techniques to reconstruct images of water, fat and silicone from a dual echo GRE. Near isotropic resolution (1.1x1.1x1.5 mm^3) can be achieved in about 2 min.

                  2106.     The Effectiveness of a Bisagittal Power Optimisation Approach in the Reduction of B1 Inhomogenity in Breast MRI at 3T

C A. Azlan^1,2, Pierluigi Di Giovanni¹, Trevor S. Ahearn¹, Wim M. Prins³, Matthew Clemence⁴, Scott I. Semple⁵, Fiona J. Gilbert¹, Thomas W. Redpath¹

¹Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Scotland, UK; ²Department of Biomedical Imaging, University of Malaya, Kuala Lumpur, Malaysia; ³Philips Healthcare, Best, Netherlands; ⁴Philips Healthcare, Reigate, England, UK; ⁵Department of Medical Physics, University of Edinburgh, Edinburgh, Scotland, UK

A major problem of 3T MRI is the increase in B1 inhomogeneity. This may affect the accuracy of quantitative and semi-quantitative analysis of DCE-MRI of the breast. To minimise this, Philips Medical Systems have proposed a bisagittal power optimisation (PO) approach. B1 maps were acquired using the conventional PO approach, for transverse imaging, and the bisagittal approach, for sagittal imaging, for 25 healthy volunteers. We show that by using bisagittal PO, the B1 field inhomogeneity is significantly reduced across the field of view. We conclude that by using sagittal imaging and bisagittal PO some implementations of DCE-MRI at 3T could be improved.

                  2107.     Automatic Correction of Intensity Inhomogeneity in Two-Point Dixon Fat and Water Images

Sungheon Kim¹, Jian Xu², Linda Moy¹, Henry Rusinek¹, Daniel K. Sodickson¹

¹Center for Biomedical Imaging, Department of Radiology, New York University, New York, NY, USA; ²Siemens Medical Solutions USA Inc., New York, NY, USA

Two-point Dixon method is often a preferred choice for clinical applications as shorter scan time reduces the motion artifacts which can cause processing failure. However, the fat quantification using two-point Dixon can suffer from intensity inhomogeneity due to imperfect compensation for the magnetic field inhomogeneity. The objective of this study was to develop a novel image processing method to correct the intensity inhomogeneity in two-point Dixon fat and water images by using their relationship with the fat and water fraction images to estimate the correction map. The proposed method was successfully developed and applied to the breast fat/water imaging.

                  2108.     Effect of B₁ Inhomogeneity-Correction on T₁-Uniformity in Breast MRI at 1.5 Tesla:  Preliminary Results

Riham H. El Khouli¹, David Michael Thomasson¹, Yuxi Pang², David Bluemke¹

¹Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, USA; ²Philips Healthcare, Cleveland, OH, USA

It has been shown that b1 inhomogeneity can affect quantitative evaluation of dynamic contrast enhanced MRI of the breast at high fields, we show that it is also important at 1.5 Tesla. B1 field maps can correct for spatially varying flip angles and consequently improve T1 maps and subsequent Gd concentrations calculated from the baseline T1 Since B1 terms are used in calculating the T1 map and in the subsequent calculation of Gd concentration, these measures may be more robust in determining simple enhancement ratios as well as the more sophisticated pharmaco-kinetic based permeability maps.

                  2109.     Kinetic Curves of Malignant Lesions Are Not Consistent Across MR Systems: The Need for Improved Standardization of Breast DCEMRI Acquisitions.

Sanaz Arkani Jansen¹, Akiko Shimauchi, Lindsay Zak, Xiaobing Fan, Abbie Wood, Gregory Karczmar, Gillian Newstead

¹University of Chicago, Chicago, IL, USA

Standardization of breast dynamic enhanced MR imaging (DCEMRI) protocols is not widespread at this time, with several different manufacturers and imaging protocols being implemented routinely. Radiologists and imaging physicists should expect that breast lesions appear similarly in all clinical acquisitions, so that similar interpretation criteria can be applied and similar diagnostic accuracy can be achieved. Surprisingly, in this study we found that malignant lesions imaged with one system exhibit significantly lower initial uptake and decreased ‘washout’ type curves compared with two other systems. Improved standardization procedures are necessary so that all women undergoing breast DCEMRI can be imaged adequately.

                  2110.     Off-Resonance Effects of Spectrally-Selective Adiabatic Inversion Pulses in Dynamic Contrast-Enhanced Breast Examinations

Maria A. Schmidt¹, Gokhan Ertas¹, James A. D'Arcy¹, Anna M. Kirby², Geoffrey S. Payne¹, David J. Collins¹, Nandita deSouza¹, Martin O. Leach¹

¹MRI Unit/Cancer Research UK Clinical Magnetic Resonance Group, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK; ²Radiotherapy, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK

We investigate whether magnetic field inhomogeneity can cause spectrally-selective adiabatic inversion pulses to affect contrast-agent uptake curves in breast examinations. Field inhomogeneity and linewidth were measured for breast, and image intensity as a function of T1 was simulated and measured both on and off resonance. Sequence parameters must provide an approximately linear relationship between image intensity and concentration not only on resonance, but also off resonance. The off-resonance behaviour was found to differ from the on-resonance. In the presence of field inhomogeneity, sequences with spectrally selective inversion recovery are not suitable for quantitative analysis.

                  2111.     Do Advanced MRI Methods Add Value to Routine Contrast-Enhanced Breast MRI?

Frederick Kelcz¹, Catherine Moran², Karl Vigen³, Garima Agrawal³, Walter Block³

¹University of Wisconsin, Madison, WI, USA; ²University of Wisconsn, Madison, USA; ³University of Wisconsin, Madison, USA

We present preliminary results of a study in which DWI, MRS, BOLD and sub-minute resolution techniques were added to a routine clinical MRI sequence to determine if there is any added value. The most useful sequence may be DWI for atypical fibroadenomas.

                  2112.     Flexible Four Element Phased Array Coil for Supine Breast MRI

Peter Siegler¹, Gilbert Thevathasan², Cameron Piron², Helen Marshall¹, Patrick M. Devine¹, Donald Bruce Plewes¹

¹Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; ²Sentinelle Medical Inc., Toronto, Ontario, Canada

Dynamic contrast enhanced breast MRI shows a high sensitivity for breast cancer but is commonly done in a prone position which complicates its use for image-aided strategies. Recently, supine unilateral breast MRI with compensation for respiratory motion was successfully implemented. However, the first coil prototype was of a rigid design, which showed only moderate signal-to-noise (SNR) characteristics. Here, a flexible four-element receive coil was built with a fixation that allows a stable bending and rotation of the coil. This permits the changing the coil shape to match individual breast shapes substantially improving the SNR over the entire volume of interest.

                  2113.     Evaluation of Multi-Coil Breast Arrays for Parallel Imaging

Helen Marshall¹, Patrick M. Devine¹, Nishanthan Shanmugaratnam², Cameron Piron², Donald B. Plewes¹

¹Division of Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; ²Sentinelle Medical Inc, Toronto, ON, Canada

The achievable signal to noise ratio and parallel imaging performance of a given imaging sequence are strongly dependent on the radio-frequency coil array used to collect the data. Two commercially available 8-element coils and a prototype 16-element coil were compared. Their performance for both conventional and SENSE-accelerated imaging was assessed in terms of SNR, g-factor and uniformity. The 8-element coil with adjustable coils had the highest SNR, the 8-element coil with a fixed coil arrangement had the best uniformity, and the 16-element coil enabled superior acceleration in the superior-inferior direction in addition to the left-right direction compared to either 8-element coil.

                  2114.     3D Breast Segmentation for Image Based Shimming

Arjan Willem Simonetti¹, Ronald Holthuizen¹, Chiel Johannes den Harder¹, Mathijs Visser¹, Mark Limkeman¹

¹Philips Healthcare, Best, Netherlands

This paper proposes an algorithm that performs automatic delineation of the breasts, axillae and implants if present. We aim to perform segmentation on low resolution MR images which are also used for B0 map calculation, and combine the breast segment and B0 map to perform image based shimming. Optimized shimming facilitates the MR workflow by improving the quality of fat suppressed clinical images. This is especially important in the breast which often has a high fat content and a large field of view in bilateral imaging.

                  2115.     Application of Mammographic Shape Factors to Breast MRI

Eric Van Uytven¹, Hilary Alto², Lawrence Ryner¹

¹National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada; ²National Research Council Institute for Biodiagnostics (West), Calgary, Alberta, Canada

Breast MR has received a boost in popularity due to the recent recommendation of the American Cancer Society for high risk screening. However, improving specificity has remained a challenge. Studies have shown that the evaluation of morphology is an important factor in properly diagnosing a suspicious enhancing lesion. Currently, only qualitative measures are used in breast MRI lesion evaluation. This work presents the adaptation of several mammographic shape factors to breast MRI. Preliminary analysis indicates these shape factors have the potential to increase specificity. We are currently undertaking a more extensive patient study.

                  2116.     Evaluation of Automatic Breast MR Anatomy Segmentation

Jean-Michel Rouet¹, Ursula Kose², Johannes Buurman², Maxim Fradkin¹, Robert A. Schmidt³, Charlene Sennett³, Hiroyuki Abe³, Gillian M. Newstead³

¹Philips Healthcare, Paris, France; ²Philips Healthcare, Best, Netherlands; ³Department of Radiology, The University of Chicago, Chicago, IL, USA

Automation of breast MR BI-RADS reporting requires fast automatic detection and segmentation of the breast anatomy, which is particularly difficult given the large variation in anatomical details and MR imaging protocols.

                  2117.     Whole Body Diffusion Weighted Imaging/ADC Mapping and MR Spectroscopy for Detection and Monitoring of Metastatic Cancer at 3T:Preliminary Results

Michael A. Jacobs^1,2, Li Pan³, Katarzyna Macura⁴, Ronald Ouwekerk⁴, Antonio C. Wolff², Vered Stearns², Ihab Kamel⁴, Nouha Salibi³, Wilhelm Horger⁵, David Bluemke⁴, Christine Lorenz³

¹The Russell H. Morgan Department of Radiology and Radiological Science , The Johns Hopkins University School of Medicine, Baltimore , MD , USA; ²Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ³Siemens Corporate Research, Inc., Baltimore, MD, USA; ⁴The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ⁵Siemens AG Healthcare Sector, Erlangen, Germany

The ability to diagnose metastatic disease without radiation would be an advancement in the initial work-up of cancer[1]. The purpose of this study was to investigate the potential use of a novel whole body diffusion weighted imaging (WB-DWI) method coupled magnetic resonance spectroscopy (MRS) for the detection and monitoring of metastatic disease in patients and transition to 3T.

                  2118.     B0 Maps Highly Accentuate Spiculations at the Tumor Margin

Milica Medved¹, Gillian M. Newstead¹, Hiroyuki Abe¹, Olufunmilayo I. Olopade², Gregory S. Karczmar¹

¹Radiology, University of Chicago, Chicago, IL, USA; ²Medicine, University of Chicago, Chicago, IL, USA

We show that B0 mapping is highly sensitive to spiculations at the breast lesion margin. Thus, it could be used as adjunct to standard clinical imaging, for better morphological assesment. This is especially important in small lesions that present with a malignant-type contrast-enhancement curve. It can also be an important option for patients who can not use MR contrast agents.

                  2119.     MR-Guided Focused Ultrasound Surgery of Breast Cancer

Kiyoshi Namba¹, Hidemi Furuswa¹

¹Breast Department, Breastopia Namba Hospital, Miyazaki-shi, Miyazaki-ken, Japan

Experiences of noninvasive MR-guided Focused Ultrasound Surgery of breast cancer is demonstrated.

                  2120.     Development of a Tissue Susceptibility Matched Pyrolytic Graphite Foam for Improved Frequency Selective Fat Suppression in Breast MRI

Gary Chiaray Lee¹, Patrick Goodwill¹, Kevin Phuong², Brian Hargreaves³, Ben Inglis⁴, Steven Conolly^1,2

¹Berkeley/UCSF Joint Bioengineering Gradute Group, Berkeley, CA, USA; ²Bioengineering, UC Berkeley, USA; ³Radiology, Stanford University, USA; ⁴Henry Wheeler, Jr. Brain Imaging Center, UC Berkeley, USA

Robust frequency selective fat saturation techniques require uniform homogeneity of the B₀ field to correctly saturate the fat signal in MRI. Mismatched susceptibility boundaries in the body, such as those near the skin, can create steep field gradients that cannot be reliably shimmed. Here we develop tissue susceptibility matched pyrolytic graphite foams to reduce field gradients to less than 1 ppm in order to maintain a pristine field for proper frequency selective fat suppression for contrast-enhanced breast MRI. We also measure heating and conductivities to ensure clinical safety.

                  2121.     Image Based Second Order Shimming for Fat Suppressed Bilateral Breast Imaging at 3T

Michael Schär^1,2, Riham H. El Khouli³, Arjan W. Simonetti⁴, Ronald Holthuizen⁴, David A. Bluemke^1,3

¹Russel H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ²Philips Healthcare, Cleveland, OH, USA; ³Department of Radiology and Imaging Sciences, National Institute of Health/Clinical Center, Bethesda, MD, USA; ⁴Philips Healthcare, Best, Netherlands

Homogenous fat suppression is crucial in breast MRI but remains challenging at 3T due to inhomogeneities of the static magnetic field B0. In this study it is shown that localized image based 2nd order shimming based on an acquired B0-map significantly improves the quality of fat suppression in breast imaging at 3T when compared to conventional linear volume shimming, resulting in bilateral homogenous fat suppression in 88% of cases. Calculation of image based shim values for the breast was performed fully automated and without time penalty.

                  2122.     Assessment of Errors in T1 Measurement Used for Quantitative DCE-MRI: Consequences for Pharmacokinetic Modelling

C A. Azlan^1,2, Pierluigi Di Giovanni¹, Trevor S. Ahearn¹, Gordon D. Waiter¹, Scott I. Semple³, Fiona J. Gilbert¹, Thomas W. Redpath¹

¹Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Scotland, UK; ²Department of Biomedical Imaging, University of Malaya, Kuala Lumpur, Malaysia; ³Department of Medical Physics, University of Edinburgh, Edinburgh, Scotland, UK

In quantitative DCE-MRI pre-contrast T1s are normally measured using multiple flip angle FLASH with a short TR. This technique might produce errors contributed by the incomplete spoiling of transverse relaxation. We compare the T1s of gel phantoms measured using multi flip angle FLASH at short and long TR with an inversion recovery (IR) technique. We show that T1 measurement at long TR closely matches those with the IR approach. However, a short TR sequence can give errors in T1 over 100%. This error in T1 will have a direct consequence of the accuracy in pharmacokinetic parameters estimated.

                  2123.     Three Dimensional ¹H Magnetic Resonance Spectroscopy in Breast Cancer as an Indicator of Therapy Response. a Pilot Study

Stephan Gruber¹, Wolfgang Bogner², Marek Chmelik, Katja Pinker, Lothar Ponhold, Martin Krssak, Siegfried Trattnig

¹Dept. Radiology, MR-Centre of Excellence, Medical University of Vienna, Vienna, Austria; ²Dept. Radiology, MR-Centre of Excellence, Medical University of Vienna, Austria

In this study, a high resolution 3D-MRSI protocol at 3 Tesla was used in female breast cancer patients before and after treatment (chemotherapy). In total, three patients were scheduled for two or three measurements. In two patients Cho was detectable before treatment, but, after treatment, the Cho resonance was no longer detectable. In one patient Cho was detectable in all three measurements with variable SNR. Approaches for absolute quantification are necessary for future applications, which would allow more reliable monitoring of the response to chemotherapy in breast cancer.

                  2124.     Improving the Specificity of Breast MRI with Fuzzy Cluster Analysis

Eric Van Uytven¹, Iain Kirkpatrick², Lawrence Ryner¹

¹National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada; ²Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada

We demonstrate the use of fuzzy cluster analysis (FCA) to analyze dynamic, contrast-enhanced image sets obtained from clinical patients. The analysis highlights the ability of this technique to screen for contra-lateral involvement and reveal complex morphology. This technique also allows the interpreting radiologist to properly analyze tumors with complex uptake kinetics without the need to select a region-of-interest. In summary, complex uptake kinetics and morphological features can be quickly and reliably analyzed, summarized, and presented to the radiologist in a manner which allows for rapid evaluation.

                  2125.     Patient-Specific Models of Susceptibility-Induced B0 Field Variations in Breast MRI

Caroline D. Jordan^1,2, Bruce L. Daniel¹, Kevin M. Koch³, Huanzhou Yu⁴, Steven Conolly⁵, Brian A. Hargreaves¹

¹Radiology, Stanford University, Stanford, CA, USA; ²Bioengineering, Stanford University, Stanford, CA, USA; ³Applied Science Laboratory, GE Healthcare, Waukesha, WI, USA; ⁴Applied Science Laboratory, GE Healthcare, Menlo Park, CA, USA; ⁵Bioengineering, U. C. Berkeley, Berkeley, CA, USA

MRI is an important tool for diagnosing and staging breast cancer. The shape of the breast may result in susceptibility-induced field changes, which can cause poor fat-saturation artifacts near air-tissue boundaries. We developed an empirical model that predicts spatial variations in the magnetic field in the breast based on the shape of the breast. Results indicate that the simulated field map closely models the inhomogeneities of the actual field map. This simulation may provide a model for improved shimming or estimates for unwrapping frequency shifts in phase-based fat-water separation techniques. It also may contribute to understanding what fraction of the field error is due to the lungs versus the outside air.

                  2126.     Quantitative MRI Technique for Mapping the T1/T2 Ratios of Benign and Malignant Breast Lesions

M. A. Malikova¹, Jaroslaw Nicholas Tkacz², Adam Yaakil², Priscilla Slanetz³, Hernan Jara²

¹Surgery, Boston University Medical Center, Boston, MA, USA; ²Radiology, Boston University Medical Center, Boston, MA, USA; ³Radiology, Beth Israel Medical Center, Boston, MA, USA

We have developed a quantitative MRI technique for mapping the longitudinal-to-transverse relaxation times ratio (T1/T2) of benign and malignant breast lesions. This technique gives reliable quantitative results and produces high image quality on T1, T2, and T1/T2 maps, as tested on 20 female subjects with known or suspected lesions proven by biopsy and pathologic correlation. In our small series, there is a statistically significant difference in the T1/T2 ratios of benign and malignant breast lesions using this technique.

                  2127.     Small-Voxel High Spatial and Spectral Resolution (HiSS) MRI of Human Breast: A Pilot Study

Milica Medved¹, Gillian M. Newstead¹, Hiroyuki Abe¹, Abbie M. Wood¹, Akiko Shimauchi¹, Olufunmilayo I. Olopade², Stefan Fischer³, Sri Swaminathan³, Marko Ivancevic³, Gregory S. Karczmar¹

¹Radiology, University of Chicago, Chicago, IL, USA; ²Medicine, University of Chicago, Chicago, IL, USA; ³Philips Medical Systems, Cleveland, OH, USA

Small-voxel HiSS is a novel approach to MRI of the breast that is likely to increase its diagnostic utility. Twelve women were scanned using an echo-planar spectroscopic imaging-based sequence, in 1 mm thick slices with either 0.50 mm or 0.75 mm in-plane resolution, and with spectral resolution of 5 or 18 Hz, respectively. Images proportional to water resonance peak height were constructed. Even in small voxel sizes, adequate SNR, high dynamic range, uniform and complete fat suppression, and excellent contrast and margin delineation of lesion and parenchyma were achieved.

                  2128.     Susceptibility Weighted Imaging in Breast Tissue: Initial Experiences

Catherine Judith Moran¹, Matthew R. Smith¹, Frederick Kelcz², Walter F. Block^1,3

¹Medical Physics, University of Wisconsin, Madison, WI, USA; ²Radiology, University of Wisconsin, Madison, WI, USA; ³Biomedical Engineering, University of Wisconsin, Madison, WI, USA

Susceptibility Weighted Imaging has been shown to be an effective contrast mechnism for many structures. One of the limiting factors of breast MRI is the ability to depict microcalcifications. We present our first steps in the application of SWI in the breast through anaysis of the technique in healthy breast tissue.

                  2129.     In Vivo Sodium Imaging and Relaxometry of the Breast at 3T

Ernesto Staroswiecki^1,2, Anderson Nnewihe^1,3, Neal Kepler Bangerter^4,5, Bruce Lewis Daniel¹, Brian Andrew Hargreaves¹

¹Radiology, Stanford University, Stanford, CA, USA; ²Electrical Engineering, Stanford University, Stanford, CA, USA; ³Bioengineering, Stanford University, Stanford, CA, USA; ⁴Electrical and Computer Engineering, Brigham Young University, Provo, UT, USA; ⁵Radiology, University of Utah, Salt Lake City, UT, USA

Sodium MRI shows promise for breast imaging, since it does not require an exogenous contrast, and sodium signal in tumors differs from healthy glandular tissue. Sodium relaxation parameters could show differences in the lesions, and also allow sequence optimization. We show a protocol to acquire high-resolution in vivo sodium images and sodium T1 and T2* maps of glandular breast tissue at 3T, with corrections for the B1 profile of the coil. We also present preliminary results showing both the sodium signal intensity and the sodium T2* elevated values in areas corresponding to tumors when compared to healthy glandular tissue.

                  2130.     Spectrally Selective Arterial Spin Labeling Imaging for Breast Cancer Perfusion Study

Ka-Loh Li¹, Yiping Du², Evelyn Proctor¹, Xiaoping Zhu¹, Milica Medved³, Gregory Karczmar³, Nola Hylton¹

¹Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA; ²Brain Imaging Center, University of Colorado Denver School of Medicine, Aurora, CO, USA; ³Radiology, University of Chicago, Chicago, IL, USA

We propose a new approach to incorporate ASL with a breast EPSI (BEPSI) to evaluate perfusion in the spectrally segmented water and other tissues. The results show substantial improvement in restoring perfusion contrast between cancer and normal tissues. The spectrally segmented water images showed increasing blood flow in cancer focus. Fat images showed spread of neovasculature. The spatial distribution of “enhancement” of tumor rim/center different on ASL-BEPSI and CE-MRI provides additional information. In summary, the new method provides a new means to assess perfusion of breast cancers, The EPSI approach is probably the way to do breast ASL imaging.

                  2131.     Towards Practical Breast Diffusion Tensor Imaging at 3.0T in the Clinical Setting

Tom Yankeelov¹, J. Christopher Gatenby¹, E. Brian Welch², Bapsi Chakravarthy, Darla Freehardt, Ingrid Mayer, Mark Kelley, Ingrid Meszoely, John Gore¹

¹Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA; ²MR Clinical Science, Philips Healthcare, Cleveland, OH, USA

Diffusion weighted MRI (DW-MRI) is a promising surrogate biomarker for the characterization of human breast cancer. Unfortunately, the quality of DW-MRI data is frequently compromised by the presence of main magnetic field (B0) inhomogeneities which can lead to geometric distortion in the echo planar imaging (EPI) techniques typically used to acquire such data. We present preliminary evidence suggesting that correcting DW-MRI data of the breast via a B0 map can lead to superior quality data in terms of less distortion and better tumor localization.

                  2132.     Optimizing and Understanding BOLD Contrast Imaging in the Breast

Rebecca Rakow-Penner¹, Bruce Daniel¹, Gary Glover¹

¹Radiology, Stanford University, Stanford, CA, USA

Blood oxygen level dependent (BOLD) contrast imaging has the potential to evaluate tumor metabolism and angiogenesis. Our group is developing a robust method for detecting BOLD contrast in healthy breast tissue in preparation for scanning breast cancer patients. Previous results indicated the complexity of BOLD contrast imaging in the breast, motivating further evaluation of the stimulus and optimization of the overall approach. We found that BOLD contrast imaging in the breast is more readily detected using carbogen interleaved with oxygen or room air as a stimulus and that carbogen and oxygen provide opposing contrast in the breast.

                  2133.     Water/Fat Separation and Off-Resonance Correction for 3T Spiral Breast Imaging

Kristin L. Granlund^1,2, Bruce L. Daniel¹, Brian A. Hargreaves¹

¹Radiology, Stanford University, Stanford, CA, USA; ²Electrical Engineering, Stanford University, Stanford, CA, USA

Spiral imaging is plagued by blurring due to field inhomogenity and susceptibility differences. Off-resonance correction improves water/fat separation because the phase is dependent on the relative phases of fat and water. Water/fat separation in the presence of B0-inhomogeneity is especially problematic in breast imaging, where the glandular tissue of interest is surrounded by fat and the geometry causes severe field variations. We compare three different methods of estimating the field map using a least-squares method and present the results of multi-frequency reconstruction for 3T spiral breast imaging.

                  2134.     Effect of Fat Spectral Model Parameters on Hepatic Fat Quantification by Multi-Echo Gradient-Echo Magnetic Resonance Imaging

Takeshi Yokoo¹, Mark Bydder¹, Gavin Hamilton¹, Michael S. Middleton¹, Heather M. Patton², Terek Hassanein², Jeffrey B. Schwimmer³, Claude B. Sirlin¹

¹Radiology, UCSD, San Diego, CA, USA; ²Medicine, UCSD, San Diego, CA, USA; ³Pediatrics, UCSD, San Diego, CA, USA

Recently several groups suggested that accurate estimation of hepatic fat content using gradient-recalled-echo (GRE) MR imaging requires modeling of the signal interference caused by the non-dominant fat peaks as well as the dominant 1.2 ppm peak. Previously our group demonstrated high fat quantification accuracy in human subjects using non-T1-weighted multi-echo GRE imaging with a 3-peak fat spectral model. However, it is conceivable that the fat estimation accuracy depends on the choice of the model parameters. In this study, we perturbed fat spectral model and assessed its effect of fat estimation accuracy, using MR spectroscopy as the reference technique.

                  2135.     Diurnal Pattern of Hepatic Fat Content Measured by Magnetic Resonance Imaging in Human Subjects

Masoud Shiehmorteza¹, Yauk Lee¹, Gavin Hamilton¹, Michael Schroeder¹, Irene Mwangi¹, Julie Collins¹, Mark Bydder¹, Takeshi Yokoo¹, Claude B. Sirlin¹

¹Radiology, University of California San Diego, San Diego, CA, USA

Purpose: To determine whether MR imaging measurement of hepatic fat content is influenced by the time of the day or in response to transitions from fasting to fed states.

                  2136.     Evaluation of Combined Magnetic Resonance and Bioassay Methods for Quantitation of Human Liver Steatosis

Yvan Boulanger¹, Martin Ruel¹, Abdesslem Khiat¹, Luigi Lepanto¹, Miguel Chagnon², Claude Kauffman¹, An Tang¹, Louis Gaboury³, Gaspard d'Assignies¹

¹Radiologie, CHUM, Montréal, Québec, Canada; ²Mathématiques et statistique, Université de Montréal, Montréal, Québec, Canada; ³Anatomo-pathologie, CHUM, Montréal, Québec, Canada

In order to determine the most reliable noninvasive technique or combination of techniques to detect and quantitate liver steatosis, correlations were assessed with fat fractions (FF) measured by a semi-automatic segmentation of liver histopathology slices for results of dual-echo imaging (DEI), MRS, diffusion-weighted imaging (DWI) and several bioassays in 20 liver steatosis patients. Strong correlations were obtained for DEI, MRS and three bioassays but not for DWI data. Partial correlations combining two methods failed to improve the correlations with results from a single method. DEI and MRS therefore appear as the best methods to noninvasively quantify liver steatosis.

                  2137.     T1 Effect in Fat Quantification Errors in RF Saturation and IDEAL Gradient Echo Imaging

Hing-Chiu Chang¹, Chun-Jung Juan², Yin-Cheng Kris Huang³, Hsiao-Wen Chung³

¹Applied Science Laboratory, GE Healthcare Taiwan, Taipei, Taiwan; ²Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan; ³Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan

Several groups have used different MRI imaging techniques to estimate liver fat content including spectroscopic approach, opposed-phase imaging, RF saturation and three-point Dixon IDEAL. However, tissue relaxation, in particular T1, is a potential source of bias in fat quantification unless corrections are performed. In this experimental work using phantoms with long and short T1 values, we report the quantitative influences of the T1 effect on fat quantification when using RF saturation and IDEAL methods. Our results suggest fat-fraction measurement is affected by the T1 value of the tissue in a nonlinear manner, with larger bias encountered in long-T1 than short-T1 tissues. While T1 relaxation is an obvious factor that could influence accuracy in fat quantification, previous studies seldom considered the T1 effects. The results from our study show that the T1 bias in fat-fraction measurements depends on scan parameters (T1 or PD) and sequences (FSE vs. GRE), with PD-weighted images better immune to T1 biasing errors. In clinical situations where relaxation parameters may alter pathologically, therefore, T1 effects should be included in fat-fraction quantification using RF saturation and IDEAL.

                  2138.     Simultaneous Changes in Liver Volume, Lipid Content and Glycogen Content in Type 2 Diabetes, Obese Subjects and Normal Controls After a Mixed Meal

Mary Charlotte Stephenson¹, Emily Leverton¹, Eric Y. Khoo², Jane Halliday³, Simon M. Poucher³, Lars Johansson^4,5, Jan W. Eriksson^4,6, Roy Taylor⁷, Peter Mansell², Ian A. Macdonald², Peter Gordon Morris¹

¹SPMMRC, School of Physics and Astronomy, University of Nottingham, Nottingham, UK; ²School of Biomedical Sciences,, University of Nottingham, Nottingham, Nottinghamshire, UK; ³AstraZeneca, Macclesfield, UK; ⁴AstraZeneca, Molndal, Sweden; ⁵Dept of Radiology, Uppsala University Hospital, Uppsala, Sweden; ⁶Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; ⁷School of Clinical Medical Sciences, University of Newcastle, Newcastle, UK

Metabolic disturbances in diabetes are known to include impaired storage of glycogen and may include perturbed lipid metabolism. The purpose of the study was to observe changes in hepatic lipid and glycogen in response to two mixed meals, in four different groups, with varying degrees of metabolic dysfunction. Basal glycogen levels were found to be reduced in diabetic and healthy obese subjects when compared with normal weight healthy subjects. Attenuated postprandial increases also suggested lower ability to store glycogen. Increased hepatic lipid levels measured in the diabetic groups could not be explained solely by increased obesity indicating perturbed lipid metabolism.

                  2139.     High-Resolution Magic Angle Spinning 1H MRS Detects Lipid Biomarkers in Liver After High Fat Diet

Haihui Cao^1,2, Jussi Pihlajamaki³, Mary-Elizabeth Patti³, A Aria Tzika^1,2

¹NMR Surgical Laboratory, MGH & Shriners Hospitals, Harvard Medical School, Boston, MA, USA; ²Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA; ³Research Division, Joslin Diabetes Center at Harvard Medical School, Boston, MA, USA

We report that high-resolution Magic Angle Spinning (HRMAS) 1H MRS has detected lipid accumulation in liver of mice fed with high fat diet. Our findings are consistent with the hypothesis that HRMAS 1H NMR permits the identification of novel lipid biomarkers, which can allow early diagnosis and could greatly improve prognosis in obesity, insulin resistance and type II diabetes.

                  2140.     Monitoring Hepatic Lipid in Response to CB1R Inverse Agonist Treatment with MRS

Haiying Liu¹, Richard Z. Chen¹, Andrea Frassetto¹, Alise S. Reicin¹, Richard J. Hargreaves², Donald S. Williams², Tung M. Fong¹

¹Merck Research Labs, Rahway, NJ, USA; ²Merck Research Labs, West Point, PA, USA

Hepatic lipid content was measured before and after a CB1R inverse agonist (AM251) treatment with MRS in DIO mice non-invasively. Our result shows there is a relatively wide distribution in hepatic lipid content, which limits the statistical power of a cross-sectional study to resolve a change. In a typical treatment study, using this MRS method to follow liver lipid content serially and individually we were able to improve the statistical power compared with that of the cross-sectional approach. It also showed advantages of MRS in revealing the change in hepatic lipid content in a routine in vivo study involving mice.

                  2141.     An Approach to Graphically Evaluate Steatosis in Non-Alcoholic Fatty Liver Disease

Michelle Nystrom¹, Carl Yuan-Feng Lo¹, Phil W. Chu¹, Susan Moyher Noworolski^1,2, Aliya Qayyum¹

¹Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA; ²Graduate Group in Bioengineering, San Francisco & Berkeley, University of California, San Francisco

Hepatic steatosis is currently diagnosed by invasive liver biopsies, which are prone to sampling error. Dual-echo MR imaging offers a non-invasive technique that evaluates the entire liver. Signal intensity loss of the liver between the two echo images was color-coded for steatosis grades on 38 NAFLD patients and 20 healthy volunteers. Two MR readers’ interpretation of the colormaps strongly agreed with the corresponding histopathological results (κ =0.59-0.67) and each other (κ =0.89). Steatosis was considered heterogeneous in 60% of the NAFLD patients. This study showed that such colormaps can readily and easily be interpreted to assess steatosis severity and heterogeneity.

                  2142.     The Use of Heavily T1-Weighted  Sequences for Fat Quantification

Mark Bydder¹, Gavin Hamilton¹, Masoud Shiehmorteza¹, Chad Kohl², Takehi Yokoo¹, Michael S. Middleton¹, Claude Sirlin¹

¹Radiology, University of California San Diego, San Diego, CA, USA; ²Radiology, University of Arizona

When measuring fat fraction using gradient echo imaging, T1 weighting may increase SNR, however also leads to overestimation of the fat fraction. This overestimation may be predictable and easily corrected.

                  2143.     MRI Can Quantify Hepatic Steatosis for Treatment Monitoring During Pharmacological Intervention in the Ob/ob Mouse

Catherine DG. Hines¹, Huanzhou Yu², Ann Shimakawa², Rashmi Agni³, Thomas F. Warner³, Jean H. Brittain⁴, Scott B. Reeder^1,5

¹Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA; ²Applied Science Laboratory, GE Healthcare, Menlo Park, CA, USA; ³Surgical Pathology, University of Wisconsin-Madison, Madison, WI, USA; ⁴Applied Science Laboratory, GE Healthcare, Madison, WI, USA; ⁵Radiology, University of Wisconsin-Madison, Madison, WI, USA

Insulin-sensitizing drugs are commonly used to treat hepatic steatosis in NAFLD/NASH patients. The purpose of this work is 1) to use MRI to non-invasively monitor metformin treatment longitudinally in an animal model of hepatic steatosis, the ob/ob mouse, and 2) evaluate the reproducibility of imaging fat-fraction measurements in order to detect meaningful longitudinal changes in fat-fractions. MRI fat-fractions agreed with Histological grading, and a 5.3% deviation about the mean indicates a true physiological difference in hepatic fat-fraction. These results demonstrate MRI successfully monitors insulin-sensitizing treatment of hepatic steatosis and progression of steatosis in mice.

                  2144.     Liver MRI and MRS for Hepatic Fat Determination in a Multicenter Clinical Trial: Evaluation of Exam Quality in Academic and Non-Academic Centers

Mark Rosen¹, Sarah Englander¹, Harish Poptani¹, Evan Siegelman¹, James Gimpel², Dena Flamini², Matthew Parris³, Bill Sasiela³, Bruce Hillman^4,5

¹Radiology, University of Pennsylvania, Philadelphia, PA, USA; ²American College of Radiology Imaging Network, Philadelphia, PA, USA; ³Aegerion, Inc., Bridgewater, NJ, USA; ⁴Radiology, University of Virginia, Charlottesville, VA, USA; ⁵American College of Radiology, Phialdelphia, PA, USA

A fifteen-center multisite trial of hepatic MRI and MRS for liver fat determination in 470 subjects was performed for the phase II evaluation of the MTP inhibitor AEGR-733. Sites performed single voxel MRS and multiple dual-echo GRE imaging for quantifying hepatic fat. Both academic and non-academic sites were included. Analyzable MRS data was obtained in 96.3% of cases. Fully compliant MRI data sets were obtained in 90.0% of cases. Both academic and non-acadeimc sites performed equally well with respect to MRS quality. Academic sites submitted a higher percentage of protocol-compliant MRI data sets than did non-academic sites.

                  2145.     High-Throughput Automated Approach to Quantitative Evaluation of Hepatic Fat Fraction in Mice

Brittany Yerby¹, Yun Jiang¹, Farid Sari-Sarraf¹, Jeffrey Tsao¹

¹Global Imaging Group, Novartis Institutes for BioMedical Research, Inc., Cambridge, MA, USA

A robust, high-throughput, in vivo readout of liver fat contents is important for preclinical obesity and diabetes research. Here, we demonstrate an approach that transforms hepatic fat fraction measurement into a semi-automated process that achieves a daily throughput of 35 animals, including acquisition and analysis, by judiciously combining macro-driven automation, IDEAL acquisition, retrospective motion compensation, hierarchical IDEAL reconstruction and rapid interactive Matlab-driven image analysis.

                  2146.     Increase of Intrahepatocellular Lipids (IHCL) During Exercise in Healthy Volunteers

Chris Boesch¹, Andrea Egger², Roland Kreis¹, Michael Ith¹, Ina Krull², Jean-Marc Nuoffer³, Peter Diem², Christoph Stettler², Emanuel Christ²

¹Dept.Clinical Research, University Bern, Bern, Switzerland; ²Div.Endocrinology, Diabetes & Clin.Nutrition, University Hospital Bern, Bern, Switzerland; ³Dept.Clin.Chemistry, University Hospital Bern, Bern, Switzerland

Intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are both related to insulin sensitivity. This 1H-MR spectroscopy study investigates the influence of exercise on IHCL and IMCL levels in order to achieve an improved standardization of IHCL measurements and to understand the factors that increase IHCL levels. After exercise, IMCL is reduced, which contrasts to a significant increase of IHCL and of free fatty acids (FFA). The effect of increased IHCL may only partially be explained by a shrinking of hepatocites and a subsequent reduction of the water reference. It is concluded that the increased FFA levels stimulate the IHCL synthesis.

                  2147.     Assessment of Non-Alcoholic Fatty Liver Disease in Severely Obese Children Using 3.0 Tesla Magnetic Resonance Spectroscopy

Jochem Reinier van Werven¹, B. G. Koot², A. J. Nederveen³, M. A. Benninga², O. H. van der Baan⁴, T. H. Pels Rijcken⁵, P. L. Jansen⁶, J. Stoker³

¹Radiology, Academic Medical Center, Amsterdam, Noord-Holland, Netherlands; ²Paediatrics, Academic Medical Center Amsterdam, Netherlands; ³Radiology, Academic Medical Center Amsterdam, Netherlands; ⁴Heideheuvel Hilversum, Netherlands; ⁵Radiology, Tergooi Hospital Hilversum, Netherlands; ⁶AMC Liver Center/ Hepatology, Academic Medical Center Amsterdam, Netherlands

Introduction: Non-alcoholic fatty liver disease (NAFLD) is strongly related to obesity. 1H-MRS is a non-invasive method to detect fatty liver. Therefore we investigated NAFLD in obese children using 1H-MRS.

                  2148.     Fast Single Breath-Hold 3D Abdominal Spiral Imaging with Water / Fat Separation and Off-Resonance Correction

Peter Börnert¹, Stephan van Zyl², Holger Eggers¹, Peter Koken¹

¹Philips Research Europe, Hamburg, Germany; ²Technical University Hamburg-Harburg, Germany

Large volume coverage, short total scan time and robust water/fat separation are important issues in abdominal MRI. 3D single breath-hold stack of spiral imaging in combination with three-point chemical-shift encoding (IDEAL) was used to achieve high quality water/fat separation with off-resonance artifact correction. Parallel imaging was employed to improve SNR, sampling efficiency and to achieve an up-front data compression during image reconstruction reducing IDEAL reconstruction time. The combination of IDEAL, SENSE and spiral signal sampling could pave the way for interesting future water/fat resolved clinical applications.

                  2149.     The Effect of J-Coupling on Absolute Quantification of Liver Fat Using MRS: A Phantom Study.

Gavin Hamilton¹, Michael S. Middleton¹, Masoud Shiehmorteza¹, Claude B. Sirlin¹

¹Department of Radiology, University of California, San Diego, San Diego, CA, USA

PRESS and STEAM differ in their sensitivity to j-coupling, and as TE increases so does the effect of j-coupling. We examine, using a water-fat phantom, the effect of TE range on the observed T2-corrected fat-water peak area ratio at 3T. We found as either the minimum TE or range of TEs increased, the observed T2-corrected fat peak area also increased. This suggests using a short minimum TE and a narrow range of TEs to get greater accuracy, for both PRESS and STEAM.

                  2150.     Characterisation of ANIT-Induced Hepatobiliary Injury in Vivo Using ³¹P MRS and in Vitro ¹H MAS MRS

Bhavana Shantilal Solanky¹, Gina J. Sanchez-Canon¹, Jeremy F L Cobbold², Simon D. Taylor-Robinson³, Jimmy D. Bell¹, Julie C. Holder⁴, I Jane Cox², Po-Wah So⁵

¹Metabolic and Molecular Imaging Group, Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, UK; ²Imaging Sciences Department, Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, UK; ³Division of Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London, UK; ⁴Safety Assessment, GlaxoSmithKline Pharmaceuticals, Ware, UK; ⁵Biological Imaging Group, Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, UK

³¹P MRS and ¹H MAS MRS was used to study ANIT-induced hepatobiliary dysfunction in rats. Three groups of animals were fed a diet containing 0.05%, 0.04% and 0.025% ANIT for 14 days. Biliary damage was confirmed in all groups and was characterised by increased PDE due to cell degeneration, and increased PC+GPC in the higher dose groups. Hepatocellular damage was only confirmed in the 0.05% group, this corresponded to increases in PME due increased mitotic activity in the peribiliary region and increased total choline. This work supports the use of ³¹P MRS and ¹H MAS MRS to study hepatobiliary disease.

                  2151.     Comparison of Liver Fat Fraction Measured by MR Spectroscopy at 1.5T and 3T

Gavin Hamilton¹, Michael S. Middleton¹, Takeshi Yokoo¹, Alexander Kuo², Claude B. Sirlin¹

¹Department of Radiology, University of California, San Diego, San Diego, CA, USA; ²Department of Medicine, University of California, San Diego, San Deigo, CA, USA

In this study, we compare the spectroscopy-determined fat fraction given at 1.5T and 3T in human subjects examined at both field strengths on the same day. We find there is close agreement between the liver fat fraction measured by MR spectroscopic at 1.5T with that measured at 3T. For the measurements at the two field strengths to be in agreement, T2 correction is necessary.

                  2152.     "Between Weeks" Reproducibility of 3.0 Tesla Magnetic Resonance Spectroscopy for Measuring Hepatic Fat Content

Jochem Reinier van Werven¹, J. M. Hoogduin², A. J. Nederveen³, A. A. van Vliet⁴, P. Vandenberk⁵, E. S. Stroes⁶, J. Stoker³

¹Radiology, Academic Medical Center, Amsterdam, Noord-Holland, Netherlands; ²Radiology, University Medical Center Utrecht, Netherlands; ³Radiology, Academic Medical Center Amsterdam, Netherlands; ⁴PBA International, Netherlands; ⁵Johnson & Johnson Medical BV, Belgium; ⁶Vascular Medicine, Academic Medical Center Amsterdam, Netherlands

Purpose: 1H-MRS is a non-invasive method to assess hepatic fat content (HFC), but there is sparse literature addressing “between weeks” reproducibility. Methods: In 24 subjects “between weeks” reproducibility was evaluated and assessed by Coefficient of Variation (CV), Repeatability Coefficient (RC) and Intraclass Correlation Coefficient (ICC)

                  2153.     The Importance of T2-Correction in Quantifying Liver Fat Using ¹H  MR Spectroscopy

Gavin Hamilton¹, Michael S. Middleton¹, Takeshi Yokoo¹, Joel E. Lavine², Heather M. Patton³, Claude B. Sirlin¹

¹Department of Radiology, University of California, San Diego, San Diego, CA, USA; ²Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of San Diego, San Diego, CA, USA; ³Department of Medicine, University Of California, San Diego, San Diego, CA, USA

In liver ¹H MR spectroscopy, spectra are often collected at a single TE, and thus the lack of T2 correction may introduce possible confounding factors. This study collects 3T MR Spectra at multiple TEs and shows correction for T2 decay is necessary for liver fat quantification to avoid systematic over-estimate of fat fraction. Collecting multiple TE spectra also minimizes errors due to T2 variability.

                  2154.     Free-Breathing Imaging Techniques for Liver Iron Quantification: Comparison with a Validated Breath-Hold Technique in Patients with Iron Overload

Ralf Berthold Loeffler¹, Jane Hankins², Ray Song¹, Adam M. Winchell¹, Mary Beth McCarville¹, Claudia Maria Hillenbrand¹

¹Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; ²Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA

Liver iron quantification with T2* measurements is gaining clinical acceptance. So far only breath-hold techniques are validated with liver biopsies. This study compared different free-breathing techniques (regular free breathing, navigated free breathing) with a breath-hold technique that was validated with liver biopsies. Liver T2* values were very similar for the free breathing techniques and for the breath-hold technique in 3 pediatric patients with moderate to strong hepatic iron overload.

                  2155.     A Comparison Study of Liver R2* Measurement in Pediatric Patients with Iron Overload

Marine Beaumont¹, Isaac Odame², Paul S. Babyn, Logi Vidarsson, Melanie Kirby-Allen², Hai-Ling Margaret Cheng^1,3

¹Research Institute & Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada; ²Haematology/Oncology, The Hospital for Sick Children; ³Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

A rapid T2*-based method for liver iron measurement in children is desirable to avoid sedation. Twenty patients with thalassaemia major and sickle cell disease were enrolled to assess the accuracy of T2* measurements and to compare different analysis models. The commonly used constant offset model is robust to noise but tends to overestimate true iron content. The truncated model is accurate and can be optimized to measure high iron levels with appropriate echo time selection and SNR. Overall, results show that T2* measurements are as reliable as those from slower T2 acquisitions approved for MR liver iron quantification.

                  2156.     Liver T2* Measurement of Iron Overload: An Investigation of Optimal Methods of Quantification

Marine Beaumont¹, Hai-Ling Margaret Cheng^1,2

¹Research Institute & Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada; ²Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Rapid T2* measurement for iron quantification is potentially more attractive than T2-based techniques but has yet to be approved for the liver. Different analysis models are available, but their reliability under noisy conditions has not been well characterized. Three models were assessed in this study: monoexponential, constant offset, and truncated. Simulations show the truncated model to provide the best accuracy. The more common offset model suffers from overestimating true iron levels, but it retains a greater dynamic range at low SNRs. These results provide guidelines on choosing an appropriate model under specific noise conditions for accurate T2* liver iron quantification.

                  2157.     NMR-Based Metabonomics Study on Liver and Kidney Tissues from Type 2 Diabetic Mice

Shuhui Cai¹, James Y. Yang², Jingjing Xu¹, Jiyang Dong¹, Zhong Chen¹

¹Department of Physics, Xiamen University, Xiamen, Fujian, China; ²Department of Biomedical Sciences, Xiamen University, Xiamen, Fujian, China

The whole metabolite compositions in intact liver tissues and kidney tissues from db/db mice of 8 weeks old were studied by H-1 MAS NMR spectra together with principal components analysis. The liver tissues of diabetic mice have elevated level of triglyceride and declined level of trimethylamine-N-oxide, phosphocholine, glycerophosphocholine and choline, indicating significant alteration of lipid metabolism in the diabetes biochemistry. In contrast, the biochemical changes are less obvious in kidney tissues of diabetic mice. These studies may help to explore the aetiological factor of diabetes mellitus, thus assisting with the diagnosis and prognosis in clinical practice.

                  2158.     In-Vivo Manganese Enhanced Dynamic Magnetic Resonance Imaging (MEDMRI) to Evaluate Progression of Diabetes in Rodent Pancreas

Muhammad Haque^1,2, Xiaobing Fan¹, Erica J. Markiewicz¹, Lara Leoni¹, Brian B. Roman¹

¹Radiology, The University of Chicago, Chicago, IL, USA; ²Radiology, North Shore University Healthcare, Evanston, IL, USA

A lack of understanding in pathophysiological process involved in the progression of type I diabetes is an obstacle in disease management leading to other complications. Here we demonstrate the microvascular and cellular changes in pancreatic function using manganese enhanced dynamic MRI. A significantly faster Mn washout was reported in diabetic versus control pancreas. An empirical mathematical model was used to quantify Mn uptake and washout in the mouse pancreas by plotting intensity versus time. A higher temporal resolution is required to asses the Mn uptake kinetics. This technique has significant relevance in assessing novel therapies for diabetes.

                  2159.     Kinetics of Manganese Chloride in Non-CNS Organs in Mice

Li-Wen Lee¹, Po-Wah So², Anthony Price¹, Jane Halliday³, Simon M. Poucher³, John AT Pugh⁴, Cameron W. McLeod⁴, Jimmy D. Bell¹

¹Metabolic and Molecular Imaging Group, Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital Campus, Imperial College London, London, UK; ²Biological Imaging Centre, Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital Campus, Imperial College London, London, UK; ³AstraZeneca Pharmaceuticals, Macclesfield, UK; ⁴Centre for Analytical Sciences, University of Sheffield, Sheffield, UK

Similar to Ca2+, Mn2+ is taken up by activated cells where they afford signal enhancement in T1-weighted MRI methodologies. In this study we have assessed Mn2+ distribution in mice by MEMRI and absolute tissue [Mn] by ICP-ES. Our results show a linear correlation between R1 and tissue [Mn]. This provides information for optimal MnCl2 dose regimen and for MEMRI protocol for specific target organs. We also show a significant increase in pancreatic SI following glucose stimulation. This study provides a potential 3D MRI technique for in vivo surrogate imaging of Ca2+ entry during Ca2+-dependent processes in a wide range of tissues.

                  2160.     Metabolic Profiles of Urine and Serum from Type 2 Diabetic Mice Detected by ¹H NMR Spectra

Jingjing Xu¹, Jiyang Dong¹, Shuhui Cai¹, Zhong Chen¹

¹Department of Physics, Xiamen University, Xiamen, Fujian, China

Information of the whole endogenous metabolic variations caused by type 2 diabetes mellitus is of great value for discovering the primary aetiological factor of diabetes mellitus. Here metabolic profiles of urine and serum samples from type 2 diabetic mice of 8 weeks old were studied by H-1 NMR spectra together with principal components analysis. Both samples can be discriminated clearly from the control group. A number of characteristic metabolites contributed to class separation were identified and analyzed. These results indicate significant alterations in metabolic profiles of urine and serum at the insulin resistance stage of type 2 diabetic animals.

                  2161.     Effects of Catch-Up Growth at Early Age on Body Composition

Gina Julieth Sanchez Canon¹, Jelena Anastosovska¹, Po-Wah So², Neena Modi³, Elizabeth Louis Thomas¹, Jimmy D. Bell¹

¹Metabolic and Molecular Imaging Group, Imaging Science Department, MRC Clinical Science Centre, Hammersmith Hospital, Imperial College London, London, UK; ²Biological Imaging Centre, Imaging Science Department, MRC Clinical Science Centre, Hammersmith Hospital, Imperial College London, London, UK; ³Faculty of Medicine, Chelsea and Westminster Hospital, Imperial College London, London, UK

                  2162.     Investigating the Metabolism and Fate of 13C-Hyperpolarized Cis- & Trans-Fatty Acids Via 13C-MRI / MRS

Joachim Bargon¹, Rahim R. Rizi²

¹Institute of Physical Chemistry, University of Bonn, Bonn, Germany; ²Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA

Fatty acids are important for human nutrition. Disorders in their metabolism cause a variety of severe diseases. Of particular interest are differences due to the cis- and trans-steric isomers of unsaturated and multiply unsaturated varieties. Using 1H- and 13C-hyperpolarized fatty acids, their metabolites and their intermediates generated via Parahydrogen Induced Polarization (PHIP) as molecular probes and messengers to follow their fate and metabolism in the body provides detailed information about their conversions. Whereas the 13C-hyperpolarized cis-isomers of mono-unsaturated fatty acids are readily accessible using standard Rh-hydrogenation catalysts, unique Ru-catalyst are required to provide the corresponding trans forms.

                  2163.     The Effect of Stretching Exercise Amplifying Extromyocellular Lipid Signal Intensity in Proton MRS and Its Role in Exercised-Muscle T2w MRI Image

Jimin Ren^1,2, A. Dean Sherry^1,3, Craig R. Malloy^1,4

¹Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; ²Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; ³ Department of Chemistry, University of Texas at Dallas, Richardson, TX, USA; ⁴VA North Texas Health Care System, Dallas, TX, USA

The phenomenon of exercised-induced muscles intensity increase on T2w images has attracted numerous research interests due to its potential applications in clinical diagnosis of muscle diseases, exercise trainings and assessment of physical therapy. However, the underlying physiological mechanisms are still poorly understood. Traditional explanation is that it is a purely water related phenomenon, possibly resulting from water T2 elongation. MRI and 1H MRS data in this work indicate that calf muscle stretching can amplify the signal intensity of extramyocellular lipid (EMCL), likely due to fat tissue aligning along Bo direction. It may be responsible, at least partly, for the well-known effect.

                  2164.     Prolongation of Pancreatic Islet Transplant Viability: Comparison of Preservation Methods by Phosphorus Magnetic Resonance Spectroscopy

Alan Bainbridge¹, Aditya Agrawal², Stephen Powis², Ernest Cady³, Barry Fuller², Brian Davidson²

¹Medical Physics & Bio-Engineering, UCL Hospitals NHS Foundation Trust, London , UK; ²University Department of Surgery, Royal Free and University College of London Medical School, London, UK; ³Medical Physics & Bio-Engineering, UCL Hospitals NHS Foundation Trust, London, UK

Minimizing pancreatic cold preservation injury is critical for successful islet of Langerhans transplantation. In the two-layer method (TLM) of organ preservation, developed to minimize the detrimental effect of cold ischaemia, the pancreas is maintained at the interface between perfluorocarbon and a conventional preservation solution. This study aimed to develop an experimental model for dynamic assessment of pancreatic energy metabolism throughout preservation using phosphorus (31P) magnetic resonance spectroscopy (MRS). TLM prolongs rat pancreas viability better than Marshall’s solution alone. Continuous preservation-medium oxygenation increases the duration of this beneficial effect.

                  2165.     Assessment of Metabolism in the Regenerating Mouse Liver by  ³¹P MRSI

Khushali Kotedia¹, Jadegoud Yaligar¹, Kaitlyn Kelly², Joyce Wong², Jason A. Koutcher¹, Yuman Fong², Kristen L. Zakian¹

¹Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, USA; ²Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA

Levels of ³¹P metabolites in the mouse liver following partial hepatectomy (70% PH) were quantitated by ³¹P magnetic resonance spectroscopic imaging (MRSI) to determine whether ³¹P metabolites were non-invasive markers of regenerative status. In each of the 2 phases of this study, the mean NTP level decreased after PH but did not differ significantly from controls. Significant changes in PME and/or PE and PC were not observed. SNR limitations due to the very small liver remnant volume as well as inter-subject heterogeneity may have resulted in statistical uncertainty that obscured the detection of metabolic changes.

                  2166.     A 3-Liter Capacity, Hybrid Spin-Exchange ³He Polarizer for Medical Imaging

Karen E. Mooney¹, G. Wilson Miller², Peter A. M. Dolph¹, William Alexander Tobias¹, Vladimir Nelyubin¹, Jaideep Singh¹, John P. Mugler III², Gordon D. Cates^1,2

¹Physics, University of Virginia, Charlottesville, VA, USA; ²Radiology, University of Virginia, Charlottesville, VA, USA

We will describe the design and performance characteristics of our new Hybrid ³He Polarizer. The 3L capacity device produces polarization levels approaching 60%.

                  2167.     Optimization of Lung Imaging with Hyperpolarized 3Helium Using a 32 Channel Phased Array

Florian Martin Meise¹, Julien Rivoire¹, Maxim Terekhov¹, Davide Santoro¹, Sergei Kapuk², Zahir Salhi², Klaus Gast, Wolfgang G. Schreiber¹

¹Section of Medical Physics, Department of Diagnostical and Interventional Radiology, Johannes Gutenberg University Medical School, Mainz, RLP, Germany; ²Institute of Physics, Johannes Gutenberg University, Mainz, Germany

Since two years first phased array coils for human lung imaging with hyperpolarized 3He were presented. To understand and analyse the possibilities of phased array usage in lung imaging a 32channel phased array for 3He was designed and tested with several improved scan protocols to test out limitations of this technique. Compared to standard protocols high resolution 2D and 3D imaging was successfully realised as well as dynamic imaging with high temporal and spatial resolution. The results show up improved and new ways in functional lung imaging which can increase patient comfort as well as gain of information.

                  2168.     Comparison of Different Parallel Imaging Reconstruction Methods for Hyperpolarized 3He MRI

Julien Rivoire¹, Florian M. Meise², Maxim Terekhov², Davide Santoro², Zahir Salhi³, Wolfgang G. Schreiber²

¹Section of Medical Physic, Department of Radiology,, Mainz University Medical School, Mainz, Germany; ²Section of Medical Physic, Department of Radiology, Mainz University Medical School, Mainz, Germany; ³Institute of Physics, Johannes Gutenberg University, Mainz, Germany

In order to understand the advantages and disadvantages of different data reconstruction and channels combining algorithms in case of parallel MR imaging with hyperpolarized 3He, the acquisitions using in-house built 32 channels phased array were performed with several improved scan protocols (multi-slice 2D, 3D, dynamic, 3D Diffusion). The different methods, namely mSENSE, GRAPPA with Adaptive Combine and Sum-of-Square channel combining were applied to raw data to compare the quality of reconstructed images.

                  2169.     Comparison of Parallel Image Reconstruction Methods to Acquire High Resolution ADC-Tensor Images of 3He in Human Lungs.

Maxim V. Terekhov¹, Julien Rivoire¹, Florian M. Meise¹, Davide Santoro¹, Wolfgang G. Schreiber¹

¹Department of Radiology, Section of Medical Physics, Mainz University Medical School, Mainz, Germany

Measuring the Apparent Diffusion Coefficient (ADC) of hyperpolarized 3He-gas in lungs is a proven method of non-invasive probing the integrity of lung’s microstructure. Due to sophisticated configuration of small airways the diffusion in lungs is anisotropic and can be characterized by ADC-tensor. The ADC-tensor symmetry may provide valuable additional information about the pathological changes of lung microstructure. The purpose of current work is to demonstrate the possibilities, which provides the phased-array parallel acquisition for improving the efficiency of 3He ADC-tensor measurements and to make comparison of different reconstruction methods of the parallel imaging datasets to improve quality of ADC-tensor maps.

                  2170.     Effect of Echo Spacing on the T2 of Hyperpolarized He3 in the Healthy Human Lung at 1.5T

John P. Mugler, III¹, G Wilson Miller¹, Talissa A. Altes¹, Jaime F. Mata¹, Eduard E. de Lange¹, W Al Tobias², Gordon D. Cates, Jr. ^1,2, James R. Brookeman¹

¹Radiology, University of Virginia, Charlottesville, VA, USA; ²Physics, University of Virginia, Charlottesville, VA, USA

The T2 value for He3 in the healthy human lung was measured at 1.5T using a CPMG spin-echo-train pulse sequence with echo spacings of 10, 20 and 30 ms. The mean T2 values from five subjects were 232, 182 and 160 ms for echo spacings of 10, 20 and 30 ms, respectively. There was a statistically significant decrease in the T2 value as the echo spacing increased from 10 to 20 ms, and a trend toward further decreases in T2 as the echo spacing increased from 20 to 30 ms.

                  2171.     SSFP Imaging of Hyperpolarised 3He in the Lungs at 3T

Jim M. Wild¹, Martin H. Deppe¹, Salma Ajraoui¹, Kevin Teh¹, Rob Ireland¹, Steven R. Parnell¹, Juan Parra-Robles¹

¹University of Sheffield, Sheffield, Yorkshire, UK

Although high B0 is not necessarily optimum for hyperpolarised lung imaging, it is of technical interest to evaluate the methods at higher B0. In this work a 2D SSFP sequence was evaluated for HP 3He lung MRI at the higher B0 of 3T. The results obtained with 2D SSFP in HP 3He phantoms and human lungs are compared with 2D SPGR and the effects of B0 and B1 inhomogoneity at the higher B0 are discussed.

                  2172.     Signal-To-Noise Ratio for Hyperpolarized 3He MR Imaging of Human Lungs: A 1.5 T Vs 3 T Comparison

William Dominguez Viqueira^1,2, Alexei Ouriadov¹, Rafael O’Halloran³, Sean B. Fain³, Giles E. Santyr^1,2

¹Imaging Laboratories, Robarts Research Institute, London, Ontario, Canada; ²Medical Biophysics, University of Western Ontario, London, Ontario, Canada; ³Department of Medical Physics, University of Wisconsin, Madison, WI, USA

A signal-to-noise ratio (SNR) comparison between hyperpolarized ³He lung imaging at 1.5 T and 3 T was performed using similar RF coils and identical pulse sequences and parameters in the same healthy volunteer. After correction for flip angle and different polarizations on the two systems using similar hyperpolarized gas mixture phantoms, no significant differences in SNR were found between the two field strengths at band-widths of 32 kHz and 64 kHz. The SNR may improve at 1.5 T compared to 3 T at lower band-widths possible with longer T₂* expected at lower field strength.

                  2173.     Comparison of 3He Ventilation Images at 1.5T and 3T: Increased Apparent Heterogeneity Due to Susceptibility Gradients.

Martin Heiner Deppe¹, Juan Parra-Robles¹, Salma Ajraoui¹, Stephen R. Parnell¹, Matthew Clemence², Rolf F. Schulte³, Jim M. Wild¹

¹Academic Unit of Radiology, University of Sheffield, Sheffield, Yorkshire, UK; ²Philips Medical Systems, UK; ³GE Global Research, Munich, Germany

The influence of B₀ field strength in MRI of hyperpolarized nuclei is still a matter of discussion. In this work, ³He human lung ventilation images obtained at the clinical relevant B₀ field strengths 1.5T and 3T are compared, with focus on ventilation heterogeneity. Apparent ventilation heterogeneity is assessed by the coefficient of variation (CoV) of nearest neighbor pixel intensities. For identical TE it is found that images obtained at 3T appear more heterogeneous in the same subject, due to increased susceptibility effects. This effect will have to be taken into account when comparing quantitative markers of ventilation heterogeneity.

                  2174.     Studies of Weakly Restricted Diffusion Using Hyperpolarized ³He Gas in Cylindrical Cells

Pierre-Jean Nacher¹, Kajum Safiullin¹, Geneviève Tastevin¹

¹Laboratoire Kastler Brossel, CNRS-UPMC-ENS, Paris, France

Diffusive motion of nuclei during signal acquisition has a strong impact on lung imaging with hyperpolarized helium-3. Since air space dimensions range from hundreds of microns (alveoli) to centimeters (main bronchi), free diffusion, motional averaging, or localization regimes can be encountered depending on sequence parameters and on location within the lung. We report on MR relaxometry and 1-D imaging experiments in hyperpolarized 3He confined in sealed glass cells with gas filling pressures, dimensions, and aspect ratios that allow investigations in the (weakly) restricted diffusion met in all airways larger than the acinar ones.

                  2175.     Compressed Sensing: Applications in Hyperpolarised 3He Lung MRI

Salma Ajraoui¹, Kuan J. Lee^1,2, Juan Parra-Robles¹, Martin H. Deppe¹, Steve R. Parnell¹, Jim M. Wild¹

¹Academic Unit of Radiology, University of Sheffield, Sheffield, UK; ²Dept. of Diagnostic Radiology, Medical Physics, University Hospital Freiburg, Freiburg, Germany

The purpose of this study was to investigate to feasibility of applying compressed sensing to hyperpolarised 3He gas MRI. The aspiration of this application is to reduce the number of RF excitations needed to fully reconstruct an image and to speed up the acquisition. The method was applied to reconstruction of Cartesian encoded HP 3He gas images (ventilation and ADC). HP 3He lung images appear to be compatible with the CS method and a good 2D reconstruction with relatively small error was achieved with a reduction factor of 2.

                  2176.     Generating Noble-Gas Diffusion Maps at Very Short Time Scales

Michael Carl¹, John P. Mugler III², Gordon D. Cates³, Wilson Miller²

¹GE Healthcare, Applied Science Lab, Milwaukee, WI, USA; ²Radiology, University of Virginia, Charlottesville, VA, USA; ³Physics, University of Virginia, Charlottesville, VA, USA

We developed a pulse sequence for generating diffusion maps at sub-millisecond time scales by using the diffusion-sensitizing gradients themselves to sample k-space. A 2D plane of k-space can be covered in this manner by changing the directional orientation the diffusion gradients following each excitation RF pulse. After M excitations, where M is the number of radial lines required to adequately sample k-space, we can reconstruct N distinct diffusion-weighted images. Tests in a 3He gas phantom yielded self-consistent diffusion maps, and bode well for generating diffusion maps at sub-alveolar length scales in the lung.

                  2177.     Alveolar-Duct Geometry During Expiration Via ³He Diffusion MRI

Adam Hajari¹, Dmitriy Yablonskiy^1,2, James Quirk², Alex Sukstanskii², Mark Conradi^1,2, Richard Pierce³, Gaetan Deslee³, Jason Woods^1,2

¹Physics, Washington University, St. Louis, MO, USA; ²Radiology, Washington University, St. Louis, MO, USA; ³Internal Medicine, Washington University, St. Louis, MO, USA

Acinar geometry has been the subject of several morphological and imaging studies in the past; however, little is known about how acinar microstructure changes when the lung inflates or deflates. Lung morphometry with hyperpolarized ³He diffusion MRI allows evaluation of lung microstructural geometrical parameters. We have determined these parameters during the inflation cycle at physiologically relevant volumes by ex-vivo ³He diffusion MRI in five healthy canine lungs. Our results imply that during a change in lung volume from TLC to 60% of TLC, the outer acinar airway radius changes by 16% while the alveolar wall length remains near constant.

                  2178.     Experimental Investigation of Non-Gaussian Diffusion in Hyperpolarized ³He MRI of Lungs

Salma Ajraoui¹, Juan Parra-Robles¹, Martin Deppe¹, Kevin Teh¹, Steven R. Parnell¹, John Owers-Bradley², Jim M. Wild¹

¹Academic Unit of Radiology, University of Sheffield, Sheffield, UK; ²School of Physics, University of Nottingham, Nottingham, UK

The diffusion of 3He gas in the complex geometry of the lung deviates from Gaussian behavior. In this work, we investigate experimentally the sources of non-Gaussian behavior (e.g. anisotropy, varying airway sizes, airway interconnectivity) using many b-values in well defined geometric models built from polypropylene tubing and Y-connectors. The deviation from Gaussian behavior was evaluated by fitting the signal decay to Gaussian and kurtosis models. The results suggest that for the models used in this work, the anisotropy is the most important contributor to non-monoexponential diffusion behavior.

                  2179.     Assessment of Regional Alterations of Lung Function and Structure by Hyperpolarized 3He MRI in a Murine Model of Emphysema

Kiarash Emami¹, John MacDuffie-Woodburn¹, Charles J. Kotzer², Gregory A. Logan², Stephen Kadlecek¹, Jianliang Zhu³, Stephen Pickup¹, Jiangsheng Yu¹, Matthew Stetz¹, Masaru Ishii⁴, Michael Stephen⁵, Patricia L. Podolin², Rahim Rizi¹

¹Radiology, University of Pennsylvania, Philadelphia, PA, USA; ²Respiratory Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, PA, USA; ³Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, USA; ⁴Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA; ⁵Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA

The sensitivity of two HP 3He MRI-based measurements of gas diffusivity and ventilation to elastase-induced changes in a murine model of emphysema are studied in this work. The motivation is primarily the increasing interest in assessment of pulmonary disease models, and in assessment of therapeutic interventions in transgenic murine disease models, thereby making it necessary to extend functional and structural lung imaging techniques to a smaller scale.

                  2180.     Regional MR Correlations of Lung Function and Structure in a Rat Model of Emphysema Using Hyperpolarized 3He MRI

Elaine Chia¹, Kiarash Emami¹, John MacDuffie-Woodburn¹, Stephen Kadlecek¹, Stephen Pickup¹, Jiangsheng Yu, Masaru Ishii^1,2, Jianliang Zhu³, Michael Stephen⁴, Rahim R. Rizi¹

¹Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; ²Department of Otolaryngology – Head and Neck Surgery,, Johns Hopkins University, Baltimore, MD, USA; ³Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, USA; ⁴4Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA, USA

Preliminary results show that regional MRI measurements, 3He ADC and fractional ventilation, are sensitive metrics to elastase-induced changes in rat lungs, surpassing the sensitivity of the majority of the examined PFT measurements. While PFT measurements can indicate the presence of emphysema, MRI measurements are more sensitive to changes in the lung due to the progression of the disease. Purely regional MRI analyses can allow determination between healthy and elastase cohorts.

                  2181.     Effects of Application of Positive End Expiratory Pressure on ADC in HP 3He MRI

Laura Carrero González^1,2, Thomas Kaulisch², Ignacio Rodríguez^1,3, Jose Manuel Pérez Sánchez^1,3, Germán Peces-Barba^3,4, Detlef Stiller², Jesus Ruíz-Cabello^1,3

¹Universidad Complutense Madrid, Madrid, Spain; ²Boehringer Ingelheim Pharma, Biberach an der Riss, Germany; ³CIBER de Enfermedades Respiratorias, Madrid, Spain; ⁴Fundación Jiménez-Díaz, Madrid, Spain

Apparent diffusion coefficient is a parameter used in HP 3He MRI to study, among others, the size of lung structures to establish differences between healthy and diseased animals. ADC is also sensitive to ventilation parameters. In order to visualize how changes in positive end expiratory pressure (PEEP) and breath-hold pressure affect the lung, ADC maps were acquired during the breath-hold at 10 and 25 mbar at null PEEP, PEEP equal to 5 and 10 mbar, at five time points from minute 10 to 70 of ventilation. ADC remains nearly constant over time in all measurements, but is strongly dependent on PEEP value at any breath-hold pressure. This effect may be due to the change of 3He concentration in the lung. Alveolar recruitment is also under investigation.

                  2182.     Abnormal Ventilation Assessed with Hyperpolarized 3He MRI in Young Cystic Fibrosis Patients with Normal Lung Function. Evaluation of Immediate Influence of a Single Chest Physiotherapy Session.

Elise Bannier¹, Katarzyna Cieslar¹, Karim Mosbah¹, Francoise Aubert², Francois Duboeuf¹, Zahir Salhi³, Sophie Gaillard¹, Yves Berthezène¹, Philippe Reix⁴, Yannick Crémillieux¹

¹Université de Lyon, CREATIS LRMN, Lyon, France; ²Centre d'Investigation Clinique, Lyon, France; ³Johannes Gutenberg Universität, Mainz, Germany; ⁴Service de Pédiatrie, Hôpital Femme Mère Enfant, Lyon, France

The aim of the study was to assess the ability of 3He MRI to detect lung ventilation abnormalities in pediatric patients with normal pulmonary function tests (PFT) and to observe the immediate effect of a single chest physiotherapy session (CPT). Ventilation defects were observed and quantified pre and post CPT.

                  2183.     Hyperpolarized 3He MRI Heterogeneity and Ventilation Defect Volume Correlates with Asthma Severity

Yanping Sun¹, Terence Tan¹, Sanaz Zhalehdoust-Sani², Yang-Sheng Tzeng³, Ken Lutchen², Mitchell S. Albert¹

¹Radiology, University of Massachusetts Medical School, Worcester, MA, USA; ²Biomedical Engineering, Boston University, Boston, MA, USA; ³Radiology, Brigham and Women's Hospital, Boston, MA, USA

To assess the chronic respiratory impairment in asthmatics, we performed hyperpolarized 3He MRI to image the change in ventilation distribution in asthmatic and healthy subjects at baseline, after methacholine (Mch) challenge, after deep inspirations (DI) following Mch challenge, and after Albuterol administration. The asthmatic groups showed significantly higher defect volumes and heterogeneity at baseline than healthy subjects, which was further exacerbated by Mch challenge. Unlike in healthy subjects, DIs appeared to have little impact on diminishing defect volumes and heterogeneity in the asthmatic lung. Albuterol reversed ventilation defects and heterogeneity in healthy subjects less so in severe asthmatics.

                  2184.     Using Hyperpolarized 3He MRI to Distinguish Asthmatics from Healthy Subjects

Yanping Sun¹, Stephen Krinzman², Terence Tan¹, T Bishop², A Sosa², S Rajan², A Reno¹, Y-S Tzeng³, S Zhalehdoust-Sani³, Kenneth R. Lutchen³, J M. Madison², Mitchel S. Albert¹

¹Radiology, University of Massachusetts Medical School, Worcester, MA, USA; ²Div of Pulmonary Medicine, University of Massachusetts Medical School, Worcester, MA, USA; ³Biomedical Engineering, Boston University, Boston, MA, USA

Hyperpolarized (HP) 3He MRI has been used in the past to characterize the physiology of asthmatic lungs, however, we wanted to determine whether ventilatory defects detected with 3He MRI correlate with the presence and severity of asthma. Five pulmonologists who are blinded to patient’s information evaluated the images with a scoring system that included counting of the number of defects and scoring the degree of ventilation heterogeneity. The HP 3He MR ventilation image score results indicated that the amount of ventilation heterogeneity and the number of defects correlated well with the presence and severity of asthma.

                  2185.     Regional Analysis of Gas Elimination and Redistribution in Lungs During High Frequency Oscillatory Ventilation Studied with  Hyperpolarized ³He MRI

Maxim V. Terekhov¹, Alexander W. Scholz², Julien Rivoire¹, Lars Lillpopp², Ursula A. Wolf¹, Wolfgang Schreiber¹

¹Department of Radiology, Section of Medical Physics, Mainz University Medical School, Mainz, Germany; ²Department of Anesthesiology, Mainz University Medical School, Mainz, Germany

MRI using hyperpolarized helium-3 as a contrast gas allows studying lung air-spaces in high temporal and spatial resolution. Applying this imaging technique we aimed to quantify the regional time constants of the inert gas elimination by high-frequency oscillatory ventilation (HFOV). Additionally, we strived at the time constants of regional redistribution within the lungs using regional and pixel based mapping.

                  2186.     3He NMR Washout Monitoring Combined with 3He Ventilation MRI: Initial Experience in Healthy Volunteers and Cystic Fibrosis

Martin Heiner Deppe¹, Juan Parra-Robles¹, Salma Ajraoui¹, Sean B. Fain^2,3, Christopher J. Taylor⁴, Kenny A. Macleod⁵, Alexander R. Horsley⁵, Jim M. Wild¹

¹Academic Unit of Radiology, University of Sheffield, Sheffield, Yorkshire, UK; ²Department of Radiology, UW Hospital, University of Wisconsin, Madison, WI, USA; ³Department of Medical Physics, University of Wisconsin, Madison, WI, USA; ⁴Academic Unit of Child Health, University of Sheffield, Sheffield, Yorkshire, UK; ⁵Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK

Inert gas washout is a well-known method for assessment of lung function, and has been demonstrated to be sensitive to obstructive airways disease. This work demonstrates inert gas washout monitored via the 3He NMR signal. It is shown that this method can be integrated with 3He MRI into a single exam using the same bolus of hyperpolarized gas. Initial results from healthy volunteers and a cystic fibrosis patient are presented. Comparisons with conventional inert gas washout measurements using SF6 are drawn. Monitoring the washout of 3He after MRI yields additional physiological information at no extra cost.

                  2187.     Hyperpolarized 3He MRI of Pulmonary Ventilation in Competitive Breath-Hold Divers During Glossopharyngeal Insufflation and Exsufflation

Yanping Sun¹, James P. Butler², Steve Loring³, Peter Lindholm⁴, Jessica Gereige⁵, Ferrigno Massimo⁶, Mitchell S. Albert¹

¹Radiology, University of Masschusetts Medical School, Worcester, MA, USA; ²Physiology, Brigham and Women's Hospital, Boston, MA, USA; ³Anesthesia, Beth Israel and Deaconess Medical Center, Boston, MA, USA; ⁴Physiology, Karolinska Institutet, Stockholm, Sweden; ⁵Radiology, Brigham and Women's Hospital, Boston, MA, USA; ⁶Anesthesiology, Brigham and Women's Hospital, Boston, MA, USA

Competitive breath-hold divers are capable of breathing maneuvers that result in extremely large or small lung volumes and transpulmonary presussures, such as glossopharyngeal insufflation (GI, also known as lung packing) and exsufflation (GE, also know as reverse lung packing). We performed hyperpolarized 3He MRI to study pulmonary ventilation of elite breath-hold divers performing these breathing maneuvers. At TLC+GI, there was an overall distension of the lungs caused by hyperinflation and a striking appearance of signal hyperintensity of the airways. Dynamic HP 3He MRI during inspiration after GE showed dramatically fewer visible airway generations than inspiration from FRC, suggesting airway closure.

                  2188.     Dynamic 3D He-3 MRI for Longitudinal Evaluation of Childhood Asthma

James H. Holmes^1,2, Rafael L. O'Halloran², Thorsten A. Bley³, Christopher J. Francois³, Mark L. Schiebler³, Robert F. Lemanske⁴, Ronald L. Sorkness^4,5, Sean B. Fain^2,3

¹Applied Science Laboratory, GE Healthcare, Madison, WI, USA; ²Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA; ³Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA; ⁴Department of Pediatric Medicine, University of Wisconsin-Madison, Madison, WI, USA; ⁵Department of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA

A method for 3D time-resolved imaging is shown for the study of asthma in pediatric subjects. This work readily accommodates variable subject breath-holds and movements during the data acquisition; and it allows detection of ventilation dynamics including dynamic gas trapping. Five pediatric subjects were imaged during a single respiratory maneuver consisting of inspiration, short breath-hold (~5-13 s), forced exhalation, and tidal breathing. Subjects were verbally coached but free to perform the exhalation as needed. The work is part of an ongoing study on the origins of childhood asthma designed to look at the mechanisms and progression of the disease.

                  2189.     Free Breathing Hyperpolarized 3He Lung Ventilation Spiral MR Imaging. Implementation and Validation on a Clinical Scanner

Elise Bannier¹, Bruno Neyran¹, Katarzyna Cieslar¹, Julien Rivoire¹, Sophie Gaillard¹, Abdulrazzaq Sulaiman¹, Emmanuelle Canet-Soulas¹, Yannick Crémillieux¹

¹Université de Lyon, CREATIS LRMN, Lyon, France

The purpose of this study was to validate in vivo on rabbits a spiral free breathing imaging protocol developed on a clinical scanner. A model of MR signal dynamics was used upstream to optimize sequence and protocol parameters and downstream to extract global physiological parameters from the acquired signal. Time resolved images were reconstructed using cine retrospective synchronization and parametric maps computed.

                  2190.     Hyperpolarized Helium-3 Ventilation and ADC MR Imaging in the Treatment of Patients with Inoperable Lung Cancer.

Jaime Mata¹, Ke Sheng², Jing Cai², Paul Read², Talissa Altes¹, Eduard de Lange¹, Klaus Hagspiel¹, William Tobias³, Gordon Cates³, James Brookeman¹, John Mugler III¹

¹Radiology, University of Virginia, Charlottesville, VA, USA; ²Radiation-Oncology, University of Virginia, Charlottesville, VA, USA; ³Physics, University of Virginia, Charlottesville, VA, USA

Non-small-cell carcinoma alters the regional anatomy and physiology of the lung. Our purpose was to investigate, using hyperpolarized (hp) He-3, the regional ventilatory and structural pulmonary changes in patients with inoperable lung carcinoma.

                  2191.     Nonlinear PO₂ Decay in Human Lungs During Long-Breath-Hold ³He MRI

Juan Parra-Robles¹, Martin Deppe¹, Salma Ajraoui¹, Kevin Teh¹, Steven R. Parnell¹, Jim M. Wild¹

¹Academic Unit of Radiology, University of Sheffield, Sheffield, UK

In this work, the global lung pO₂ decay is measured using hyperpolarized ³He MR during prolonged breath-holds in human volunteers (up to 90 s) and analyzed with both the linear and exponential models. The effect of increased initial pO₂ was also studied. The results showed that for long breath-holds it is possible to observe the non-linearity of the pO₂ decay. These measurements substantiate previous observations over shorter breath-holds in animal models. The data may be used to obtain useful information about the physiology of oxygen uptake in the lungs during apnea and provide a more realistic physical basis for imaging based models of pO₂.

                  2192.     HP ³He-MRI of the Exponential Alveolar PO₂ Decay in Human Subjects

Katarzyna Cieslar¹, Elise Bannier¹, Zahir Salhi², Sophie Gaillard¹, Philippe Reix³, Yannick Crémillieux¹

¹Université de Lyon, CREATIS-LRMN, UMR CNRS 5220 INSERM U630, Lyon, France; ²Johannes Gutenberg Universität, Mainz, Germany; ³Hôpital Femme Mere Enfant, Lyon, France

The alveolar pO2 measurement in humans is currently being performed based on the linear model of pO2 decay during apnea. The aim of this work was to verify the potential advantages of using the more physiologically appropriate exponential pO2 decay model for improving the results of pO2 mapping in humans. The quality of the parametric maps based on the exponential model was found superior to the ones obtained by using the linear model. The distributions of the parameters of interest obtained as a result of the numerical simulations confirm the trends observed in vivo.

                  2193.     Measurement of the Exponential Decay of Alveolar Partial Pressure of Oxygen Using Hyperpolarized ³He MRI in Animals and Human Subjects

Katarzyna Cieslar¹, Elise Bannier¹, Philippe Reix², Sophie Gaillard¹, Emmanuelle Canet-Soulas¹, Yannick Crémillieux¹

¹Université de Lyon, CREATIS-LRMN, UMR CNRS 5220 INSERM U630, Lyon, France; ²Hôpital Femme Mere Enfant, Lyon, France

Using 3He-MRI it is possible to locally measure the alveolar partial pressure of oxygen (pO2) and its temporal evolution during apnea. The aim of this work was to demonstrate the feasibility of using a physiologically appropriate exponential model of pO2 decay in animals and humans. The exponential model was successfully applied to measure initial pO2 and oxygen depletion time constant r in mice, rats, rabbits and humans. Numerical simulations were performed to assess when the use of the nonlinear pO2 decay model is inevitable to obtain satisfying accuracy of the measured parameters.

                  2194.     Combined Proton and HP 3He Oxygen Partial Pressure Mapping for the Evaluation of Acute Respiratory Distress Syndrome

Elise Bannier¹, Katarzyna Cieslar¹, Sophie Gaillard¹, Abdulrazzaq Sulaiman¹, Emmanuelle Canet-Soulas¹, Yannick Crémillieux¹

¹Université de Lyon, CREATIS LRMN, Lyon, France

Acute Respiratory Distress Syndrome (ARDS) can result from multiple factors such as pulmonary infection, gas inhalation or drowning. In this work, proton and hyperpolarized 3He MRI were applied in a rabbit model of ARDS. Alteration of ventilation and gas exchange were observed and quantified using both oxygen partial pressure and oxygen depletion rate maps and compared to inflammation extent on proton images.

                  2195.     Detection and Evaluation of Impact of Instilled Carbon Nanotubes. a 3-Months Follow-Up Investigation Using Helium-3, Proton Lung MR, Optical and Electronic Microscopy

Achraf Al Faraj¹, Amine Bessaad², Katarzyna Cieslar², Simone Peyrol³, Ghislaine Lacroix⁴, Emmanuelle Canet-Soulas², Yannick Crémillieux²

¹Université Lyon1, CREATIS-LRMN, CNRS 5220, INSERM U630 , Lyon, France; ²Université Lyon1, CREATIS-LRMN, CNRS 5220, INSERM U630, Lyon, France; ³CeCIL Centre Commun d'Imagerie Laennec, Lyon, France; ⁴Institut National de l'Environnement et des Risques Industriels, Verneuil-en-Halatte, France

In this multi-modality study, the biodistribution and biological impacts of intrapulmonary instilled single-walled carbon nanotubes were assessed using free-breathing 3He and proton lung MRI combined to ex-vivo optical and electron microscopy in a 3-months longitudinal study. SWCNT detection with 3He MRI relied on the magnetic susceptibility effects induced by iron impurities in a dose dependant manner. Proton MRI revealed the presence of small detectable inflammatory nodules one month after 0.5 and 1-mg SWCNT instillation, which is confirmed by the presence of multifocal granulomas in histopathological analysis and collagen fiber deposition with an increased number of inflammatory cells in electron microscopy.

                  2196.     Image Registration for Quantitative Analysis of 3He MRI of the Mouse Lung

S. Sivaram Kaushik¹, Nilesh Mistry^1,2, Abraham C. Thomas², Bastiaan Driehuys²

¹Biomedical Engineering, Duke University, Durham, NC, USA; ²Center for In-Vivo Microscopy, Duke University, Durham, NC, USA

3He MRI is increasingly useful for regionally evaluating ventilation in mouse models of asthma before and after challenge with Methacholine (MCh). Such changes can be effectively quantified by suitably normalizing the pre- and post-MCh images, and subtracting the two to generate a difference map depicting regional changes in ventilation. However, difference mapping can in some instances be confounded by even sub-millimeter changes in the animal’s position between the two images. This problem can be addressed by registering the two 3He images to a common coordinate space without obscuring arising ventilation defects. Here, our approach has been described.

                  2197.     Towards Automatic Image Registration of Hyperpolarized ³He MRI and X-Ray CT Images of the Lung

Rob H. Ireland^1,2, Neil Woodhouse¹, James A. Swinscoe², Matthew Q. Hatton², Jim M. Wild¹

¹Academic Unit of Radiology, University of Sheffield, Sheffield, UK; ²Academic Unit of Clinical Oncology, University of Sheffield, Sheffield, UK

This work demonstrates the feasibility of a method of rigid image registration of hyperpolarized helium-3 MRI to inspiration breath hold x-ray CT via an intermediate breath hold 1H MRI. The approach is demonstrated for a set of nine lung cancer patients.

                  2198.     Reproducibility and Volume-Dependency of Regional Measurements of Lung Ventilation by Hyperpolarized 3He MRI

Kiarash Emami¹, Stephen Kadlecek¹, John MacDuffie-Woodburn¹, Jianliang Zhu², Stephen Pickup¹, Jiangsheng Yu¹, Matthew Stetz¹, Masaru Ishii³, Michael Stephen⁴, Rahim Rizi¹

¹Radiology, University of Pennsylvania, Philadelphia, PA, USA; ²Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, USA; ³Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA; ⁴Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA

This work assesses the reproducibility of measurements of lung ventilation and their dependency on the administered hyperpolarized 3He volume using a serial ventilation sequence.

                  2199.     T2* Mapping of Hyperpolarized 3He in the Rat Lung Using a 3D Cones Imaging Strategy

Jian-Xiong Wang¹, Jeffrey A. Stainsby², Alexei V. Ouriadov³, Matthew Fox³, Giles E. Santyr³

¹Applied Science Laboratory, GE HEALTHCARE, London, Ontario, Canada; ²Applied Science Laboratory, GE HEALTHCARE, Toronto, Ontario, Canada; ³Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada

The 3D Cones sequence utilises a central-out k-space trajectory that does not require field gradients prior to sampling. This characteristic can reduce unwanted diffusion weighting in hyperpolarized noble gas (HNG) imaging. As well, the ultra-short TE (<0.1ms) capability of the 3D Cones provides useful approach for measurement of short T2* relaxation of HNG in the lung tissues. This work presents the application of 3D Cones pulse sequence to hyperpolarized 3He gas imaging for measurement of lung volume and T2* mapping of hyperpolarized 3He gas in the rat lung.

                  2200.     Optimization of Regional Measurements of Lung Ventilation in Presence of Uncertain Model Parameters

Kiarash Emami¹, Jiangsheng Yu¹, Stephen Kadlecek¹, John MacDuffie-Woodburn¹, Jianliang Zhu², Stephen Pickup¹, Matthew Stetz¹, Masaru Ishii³, Michael Stephen⁴, Rahim Rizi¹

¹Radiology, University of Pennsylvania, Philadelphia, PA, USA; ²Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, USA; ³Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA; ⁴Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA

The accuracy of measurements of regional lung ventilation using a sequential series of hyperpolarized 3He breaths highly depends on the applied RF pulse flip angle. Assessment of optimum flip angle subject to a satisfying performance index in presence of model parameter uncertainty is the subject of this study.

                  2201.     Modeling Dead Space in Measurements of Pulmonary Ventilation Using Hyperpolarized 3He MRI

KiaRash Emami¹, Masaru Ishii^1,2, Stephen Kadlecek¹, John MacDuffie-Woodburn¹, Jianliang Zhu³, Stephen Pickup¹, Jiangsheng Yu¹, Matthew Stetz¹, Michael Stephen⁴, Rahim Rizi¹

¹Radiology, University of Pennsylvania, Philadelphia, PA, USA; ²Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA; ³Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, USA; ⁴Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA

The dead space volume in measurements of lung ventilation using gaseous contrast agents can be a substantial source of error if their magnitude is not carefully incorporated in the gas distribution model. This work presents a three-compartment model to include both static and dynamic dead volumes of the ventilation and pulmonary system and to correct for their effects in regional measurements of lung ventilation using hyperpolarized 3He MRI.

                  2202.     A Branching-Tree Lung Phantom for Hyperpolarized Noble Gas MRI

Juan Parra-Robles¹, Salma Ajraoui¹, Martin Deppe¹, Kevin Teh¹, Steven R. Parnell¹, Jim M. Wild¹

¹Academic Unit of Radiology, University of Sheffield, Sheffield, UK

In this work, we describe the construction of a simple branching-tree lung phantom made of commercially available polypropylene Y-connectors that can be easily reproduced in any laboratory. Preliminary experimental results obtained with a phantom consisting of five airway (Y-connectors) generations (inner diameter: 1.5–4 mm) using hyperpolarized ³He are reported, including dynamic ventilation imaging and diffusion measurements. The results obtained demonstrate that this phantom is a valid physical model that can be used to validate the predictions of theoretical and numerical simulations in hyperpolarized gas lung MRI and to assess the spatial resolution of the imaging methods down to 1 mm.

                  2203.     A 32 Channel Phased Array Lung Coil for Parallel Imaging with Hyperpolarized Xenon 129 at 3T

Isabel Maria Anna Dregely¹, Graham C. Wiggins², Iulian C. Ruset^1,3, John R. Brackett³, Steve Ketel³, Jan H. Distelbrink³, Vijay Alagappan², Azma Mareyam², Andreas Potthast⁴, Jonathan Polimeni², Lawrence L. Wald^2,5, Kai Ruppert⁶, Talissa A. Altes⁶, John P. Mugler III⁶, F W. Hersman^1,3

¹Physics, University of New Hampshire, Durham, NH, USA; ²Radiology, MGH Martinos Center, Charlestown, MA, USA; ³Xemed LLC, Durham, NH, USA; ⁴Siemens Medical Solutions, Erlangen, Germany; ⁵Division of Health Sciences and Technology, Harvard-MIT, Boston, MA, USA; ⁶Radiology, University of Virginia, Charlottesville, VA, USA

Parallel imaging is successfully used in combination with hyperpolarized gas MRI. The accelerated techniques allow for shorter breath holds for lung imaging which is highly desirable when imaging patients with lung disease or children. We present a 32 channel receive coil in combination with a Helmholtz transmit coil for hyperpolarized xenon imaging at 3T. Coil performance is demonstrated with 2D and 3D ventilation images acquired with TrueFISP and 2D GRE multislice sequences on a healthy volunteer.

                  2204.     Investigation of Narrowed Lasers and Cell Heating in 129Xe Optical Pumping

Steven Richard Parnell¹, Martin H. Deppe¹, Stephen Boag², Salma Ajraoui¹, Juan Parra-Robles¹, Jim M. Wild¹

¹Unit of Academic Radiology, University of Sheffield, Sheffield, South Yorkshire, UK; ²ISIS, Rutherford Appleton Laboratory, Didcot, Oxfordshire, UK

The aim of this work was to evaluate the use of narrowed high power laser systems in the optical pumping of 129Xe at ~2.5Bar. For this work we have investigated the alkali metal polarisation and light absorption in order to assess the advantages of using a narrowed pumping source. These simple and inexpensive diagnostic measurements have allowed us to quickly optimise the optimum temperature for optical pumping at this cell pressure, as evidenced by the NMR measurements presented.

                  2205.     Direct Gas Infusion of Hyperpolarized ¹²⁹Xe Into Blood—A New Approach to Imaging Pulmonary Perfusion and Gas Exchange

Harald E. Möller^1,2, Zackary I. Cleveland¹, Laurence W. Hedlund¹, Boma Fubara¹, Gary P. Cofer¹, Bastiaan Driehuys¹

¹Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC, USA; ²Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Imaging pulmonary perfusion using venous injection of hyperpolarized (HP) ¹²⁹Xe dissolved in saline was recently demonstrated. However, relatively large volumes of saline are required for this procedure and this ultimately limits the achievable image resolution. In the present study, we circumvent this problem using extracorporeal circulation of the blood through a gas exchange membrane to continuously return to the animal, blood enriched with HP ¹²⁹Xe for imaging gas exchange processes in the rat. This continuity of signal increases the available imaging time and should enable high-resolution MRI of perfusion.

                  2206.     Dissolved Phase MR Imaging of Continuously Infused Hyperpolarized ¹²⁹Xe Using Hydrophobic Gas Exchange Membranes

Zackary I. Cleveland¹, Harald E. Möller^1,2, Laurence W. Hedlund¹, Gary P. Cofer¹, Boma Fubara¹, Bastiaan Driehuys¹

¹Center for In vivo Microscopy, Duke University Medical Center, Durham, NC, USA; ²Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Because of its solubility in tissues and sensitivity to the local chemical environment, hyperpolarized (HP) 129Xe may become a powerful MRI contrast agent. For this potential to be realized, however, techniques to deliver HP 129Xe to the blood with high non-equilibrium polarization must be developed. Toward this end, a novel method of continuously infusing hyperpolarized 129Xe into flowing aqueous solutions, including whole blood, based upon microporous hydrophobic gas exchange membranes is introduced. With proper optimization, the signal intensity observed from HP 129Xe in solution is sufficient to produce dissolved phase 129Xe MR images with sub-millimeter resolution.

                  2207.     T2* for Hyperpolarized Xe129 in the Healthy Human Lung at 1.5T and 3T

John P. Mugler, III¹, Isabel M. Dregely², Talissa A. Altes¹, Stephen Ketel³, Iulian C. Ruset^2,3, Jan H. Distelbrink³, Yulin Chang¹, Jaime F. Mata¹, F William Hersman^2,3, Kai Ruppert¹

¹Radiology, University of Virginia, Charlottesville, VA, USA; ²Physics, University of New Hampshire, Durham, NH, USA; ³Xemed, LLC, Durham, NH, USA

T2* maps were obtained for Xe129 in the healthy human lung at 1.5T and 3T. The mean T2* values were 50.4 and 27.4 ms at 1.5T and 3T, respectively. The mean T2* value for Xe129 at 3T was essentially the same as that reported for He3 at 1.5T. The longer T2* for Xe129 at a given field strength will permit the data sampling periods (receiver bandwidths) used for Xe129 to be longer (lower) than those suitable for He3.

                  2208.     Q-Space Velocimetery Methods Applied to Flowing Hyperpolarized Xenon

Wilson Barros¹, Ross William Mair¹, Matthew S. Rosen^1,2, Ronald Lee Walsworth^1,2

¹Harvard-Smithsonian Center for Astrophysics, Cambridge, MA, USA; ²Dept. of Physics, Harvard University, Cambridge, MA, USA

There has been recent interest in the use of MR velocimetery techniques to study flow of hyperpolarized noble gases with the aim of elucidating flow patterns in human airways during inhalation. We apply the Fourier-encoding (q-space) velocimetery method, which yields an image of the velocity spectrum for spins in the region of interest rather than a single value of velocity, to flowing hyperpolarized xenon gas. Both the spread of the probability distribution of velocities, and the signal attenuation from a double-PGSE experiment, allows discrimination between coherent and turbulent flows, and the effects of Brownian motion from dispersion.

                  2209.     Hyperpolarized ¹²⁹Xe Lung MRI with TrueFISP on Spontaneous Breathing Mice by Means of Continuous Delivery of Xe Gas Polarized Under Low Pressure

Hirohiko Imai^1,2, Fumito Imai², Tsuyoshi Ito², Ryosuke Kashiwagi², Toshio Kadobayashi², Atsuomi Kimura², Hideaki Fujiwara²

¹Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan; ²Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

Hyperpolarized ¹²⁹Xe trueFISP images are examined on spontaneous breathing mice using the low-pressure and continuous-flow type ¹²⁹Xe polarizer toward the development of a fully non-invasive method for lung functional imaging. With the aid of the fast imaging sequence and the high-performance ¹²⁹Xe polarizer, temporal resolution and SNR have been extremely improved in the resulting images. By exploiting these characteristics, ¹²⁹Xe lung images at maximum inspiratory and expiratory phases were successfully obtained from rapidly breathing mice.

                  2210.     Hyperpolarized Xe129 Ventilation Imaging Using an Optimized 3D Steady-State Free-Precession Pulse Sequence

John P. Mugler, III¹, Talissa A. Altes¹, Iulian C. Ruset^2,3, Stephen Ketel³, Jan H. Distelbrink³, Yulin Chang¹, Jaime F. Mata¹, F William Hersman^2,3, Kai Ruppert¹, Isabel M. Dregely²

¹Radiology, University of Virginia, Charlottesville, VA, USA; ²Physics, University of New Hampshire, Durham, NH, USA; ³Xemed, LLC, Durham, NH, USA

The purpose of this work was to explore the potential of using a 3D steady-state free-precession (SSFP) pulse sequence for ventilation imaging with Xe129. We found that an optimized implementation of 3D-SSFP imaging combined with ~0.5 L of Xe129 polarized to 20% provided good quality 3D ventilation images of the lung with 6-mm isotropic spatial resolution. These results demonstrate that Xe129 ventilation images can be obtained with quality and spatial resolution similar to that demonstrated by using He3.

                  2211.     Chemical Shift Imaging of the Lungs with Hyperpolarized Xe-129: Results from a Rabbit Model of Stereotactic Lung Radiosurgery with and Without a Radioprotector.

Jaime Mata¹, Ke Sheng², Paul Read², Kai Ruppert¹, Klaus Hagspiel¹, Talissa Altes¹, William Tobias³, Gordon Cates³, James Brookeman¹, John Mugler III¹

¹Radiology, University of Virginia, Charlottesville, VA, USA; ²Radiation-Oncology, University of Virginia, Charlottesville, VA, USA; ³Physics, University of Virginia, Charlottesville, VA, USA

Recently it was shown that an optimized version of a CSI pulse sequence can produce images of hyperpolarized Xe-129 with high in-plane spatial resolution during a single breath-hold. Here, we used the same sequence to evaluate a rabbit model of lung stereotactic-radiation surgery with and without a radioprotector. Xe-129 CSI detected radiation-induced pulmonary injury at 4 and 8 weeks post-treatment, and was able to detect reduced early treatment toxicity as a result of a clinically used radioprotector. This study again demonstrated the feasibility of optimizing CSI for Xe-129 to obtain spatially-localized spectral data from the lung in a breath-hold acquisition.

                  2212.     Detection of Parameters Related to Lung Functions and Structures as Applied to Emphysema Model Mice with Hyperpolarized ¹²⁹Xe MRS Observed Under Spontaneous Respiration

Hirohiko Imai^1,2, Shoko Masuda², Tsuyoshi Ito², Yuki Hori², Atsuomi Kimura², Hideaki Fujiwara²

¹Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan; ²Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

Hyperpolarized ¹²⁹Xe MRS using a chemical shift saturation recovery (CSSR) method is applied to spontaneously breathing mice, and an attempt is made to detect physiological changes encountered in emphysema model mice. Volume ratio of alveolar tissue and gas space obtained from the method was significantly smaller for the emphysema model group than that for the control group reflecting the loss of alveolar tissues caused by emphysema. Namely, the ratio is shown to be an effective biomarker for emphysema, which will be useful for drug research and development using small rodents through non-invasive detection of the pathological changes.

                  2213.     Experimental Measurements and Computer Simulation of Long-Time-Scale Hyperpolarized ³He and ¹²⁹Xe Diffusion in Human Lungs

Chengbo Wang¹, Sylvia Verbanck², John P. Mugler, III^1,3, Kai Ruppert¹, Eduard E. de Lange¹, F W. Hersman^4,5, Isabel M. Dregely⁴, Iulian Runset⁴, Stephen Ketel⁵, Talissa A. Altes¹

¹Radiology, University of Virginia, Charlottesville, VA, USA; ²Respiratory Division, Academic Hospital UZ Brussel, Brussels, Belgium; ³Biomedical Engineering, University of Virginia, Charlottesville, VA, USA; ⁴Physics, University of New Hampshire, Durham, NH, USA; ⁵Xemed LLC, Durham, NH, USA

Long-time-scale ³He and ¹²⁹Xe diffusion was measured in human lungs and found to depend strongly on diffusion time. The ADC values for both gases were one order of magnitude less than the corresponding short-time-scale ADC values. After normalization by the respective free-diffusion coefficients, ³He and ¹²⁹Xe diffusion and their dependence on time were similar, suggesting that long-time-scale ³He and ¹²⁹Xe diffusion probe similar structures. Computer simulations based on an acinar model closely matched the experimental measurements, suggesting that noble gas diffusion is in large part representative of the complex intra-acinar pathways in the lung periphery.

                  2214.     Xenon Surface Relaxivity: Potential Applications to Probing Lung Disease

Xin Zhou^1,2, Louis -S Bouchard³, David Trease^1,2, Nick Halpern-Manners^1,2, Alexander Pines^1,2

¹Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; ²College of Chemistry, University of California, Berkeley, CA, USA; ³Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA

Hyperpolarized ¹²⁹Xe T₂, ADC, XTC and CSSR imaging techniques have been used to assess the pulmonary function, however, a drawback is that for any of these methods to be quantitative, a model of the lung is required. We believe that probing lung diseases by measuring xenon surface relaxivity in alveoli could offer unique advantages towards a model-free characterization. We demonstrated the probing of xenon surface relaxivity in phantoms and discuss potential application towards monitoring physiological changes in the alveoli surface properties, such as pulmonary fibrosis which have a large effect on the surface properties of alveoli.

                  2215.     In Vivo Proton 1.5-T MR Spectroscopy of the Breast Using the Total Choline Peak Integral as a Marker of Malignancy

Giovanni Di Leo¹, Alfonso Fausto¹, Robin de Nijs², Franca Podo³, Marianne Vorbuchner⁴, Francesco Sardanelli^1,5

¹Unit of Radiology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy; ²Magnetic Resonance, Danish Research Centre, Copenhagen, Denmark; ³Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; ⁴MR Spectroscopy and Oncology, Siemens AG Medical, Application Development, Erlangen, Germany; ⁵Medical and Surgical Science, University of Milan School of Medicine, Milan, Italy

We evaluated the total choline-containing compounds peak integral as a marker of malignancy at 1.5-T proton MR spectroscopy of the breast. Forty-five spectra were analyzed. A single-voxel water- and fat-suppressed PRESS sequence was used. Reference standard was histology or negative follow-up. At ROC analysis, the optimized threshold was 1.90 arbitrary units (au) for peak integral (0.90 sensitivity, 0.92 specificity) and 0.85 au/mL for peak integral normalized for the volume of interest (0.84 sensitivity, 0.89 specificity). In vivo proton MR spectroscopy of the breast has high diagnostic performance with a whole examination time < 40 min, including MR imaging and MRS.

                  2216.     Combining Data from HR MAS MR Spectroscopy and Gene Expression Can Refine the Subclassification of Breast Cancer

Eldrid Borgan¹, Beathe Sitter², Tone Frost Bathen², Steinar Lundgren^2,3, Hilde Johnsen¹, Ole Christian Lingjærde⁴, Therese Sørlie^1,4, Anne-Lise Børresen-Dale^1,5, Ingrid Susann Gribbestad²

¹Department of Genetics, Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway; ²Department of Circulation and Imaging, NTNU, Trondheim, Norway; ³Deptartment of Oncology, St. Olavs University Hospital, Trondheim, Norway; ⁴Department of Informatics, University of Oslo, Oslo, Norway; ⁵Faculty division, The Norwegian Radium Hospital, Faculty of Medicine, University of Oslo, Oslo, Norway

Joint analysis of gene expression microarrays and HR MAS metabolic profiles reveals differences within the luminal A tumors, a gene expression-based subtype of breast cancer. The luminal A subgroup is the largest and is associated with positive ER status and relatively good prognosis. However, a certain fraction of patients with luminal A breast cancer have a poor outcome. Preliminary results of 29 tumors from breast cancer patients show that differences in biochemistry and gene expression for two subgroups of luminal A tumors, identified by their metabolic MR profiles, are connected to lipid content and apoptosis.

                  2217.     Classification and Prediction of Prognostic Factors of Breast Cancer Patients by MR Metabolomics

Guro Fanneløb Giskeødegård¹, Steinar Lundgren^1,2, Beathe Sitter¹, Hans Fjøsne³, Jostein Halgunset⁴, David E. Axelson⁵, Ingrid Susann Gribbestad¹, Tone Frost Bathen¹

¹Dept. of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; ²Dept. of Oncology, St. Olavs University Hospital, Trondheim, Norway; ³Dept. of Surgery, St. Olavs University Hospital, Trondheim, Norway; ⁴Dept. of Laboratory Medicine, Children's and Women's Health, NTNU, Trondheim, Norway; ⁵MRi_Consulting, Kingston, Canada

Predicting prognostic factors of breast cancer is important for clinical decision-making. The purpose of this study was to predict lymphatic spread and ER status of breast cancer patients using MR metabolomics, and to classify the patients according to these factors. HR MAS MR spectra of tumor tissue from breast cancer patients were obtained and further analysed by PLS and BBN. PLS analysis clustered the spectra according to lymphatic spread and ER status, and both PLS and BBN could predict the status of spectra from blind samples. MR metabolomics may thus be a tool to identify subclasses of breast cancer patients related to prognosis and outcome.

                  2218.     Early Prediction of Nodal Status Following Neoadjuvant Chemotherapy Treatment of Breast Cancer Utilising MR Parameters

Martin D. Pickles¹, Gary P. Liney¹, Martin Lowry¹, Lindsay W. Turnbull¹

¹Centre for MR Investigations, University of Hull, Hull, East Yorkshire, UK

Malignant axillary lymph nodes (ALN) status following neoadjuvant chemotherapy (NAC) is the most significant predictor of a reduced survival interval for breast cancer patients. The purpose of this work was to determine if MR parameters obtained prior to and early during NAC could predict ALN status following NAC. If successful, treatment could be altered to increase the likelihood of a negative ALN status at surgery. The results form this study indicate that a combination of the baseline apparent spin-spin relaxation rate and changes in tumour volume at the second treatment cycle best predict ALN status.

                  2219.     Diffusion Weighted Imaging, ADC Mapping, and Sodium MR Imaging of Operable Breast Cancer After Neoadjuvant Therapy: Preliminary Results

Michael A. Jacobs^1,2, Ronald Ouwekerk³, Vered Stearns⁴, Katarzyna Macura³, Antonio C. Wolff⁴, Riham El Khouli³, Ihab Kamel³, David Bluemke^3,5

¹The Russell H. Morgan Department of Radiology and Radiological Science , The Johns Hopkins University School of Medicine, Baltimore , MD , USA; ²Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore , MD , USA; ³The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ⁴Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ⁵Radiology, NIH Clinical Center, Bethesda , MD

To prospectively investigate the feasibility of using magnetic resonance imaging (MRI) Diffusion Weighted imaging (DWI) with ADC mapping and sodium imaging (23NA) before (baseline) and after preoperative systemic treatment (PST) in breast cancer.

                  2220.     Multinuclear and Multiparametric MR Imaging as an Early Treatment Response Biomarker for Preoperative Systemic Therapy in Breast Cancer:Preliminary Results

Michael A. Jacobs^1,2, Ronald Ouwekerk³, Antonio C. Wolff⁴, Vered Stearns⁴, Katarzyna Macura³, Ihab Kamel³, Zaver M. Bhujwalla^2,3, David Bluemke³

¹The Russell H. Morgan Department of Radiology and Radiological Science , The Johns Hopkins University School of Medicine, Baltimore , MD , USA; ²Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore , MD , USA; ³The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ⁴Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Combined proton (1H) imaging and sodium (23Na) imaging will provide a comprehensive description of the tumor microenvironment in order to assess response to therapy in operable breast cancer in order to predict therapeutic response.

                  2221.     Evaluation of Computer Aided 3D Parametric Analysis of MR-Mammography for Follow-Up Assessment of Malignant Lesions Under Primary Systemic Therapy

Lale Umutlu¹, Stefan Maderwald¹, Till A. Heusner¹, Sherko Kuemmel², Rainer Kimmig², Elke Hauth¹, Michael Forsting¹, Thomas C. Lauenstein¹

¹Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, NRW, Germany; ²Department of Gynaecology and Obstetrics, University Hospital Essen, Essen, NRW, Germany

Apart from non-melanoma skin cancer, breast cancer is currently the most common cancer type among women. In case of multricentric or inoperable tumor manifestation neoadjuvant chemotherapy is used for preoperative tumor size reduction. Hence, the evaluation of early treatment response is an inevitable issue in primary systemic therapy. Computer aided detection systems provide a fast and reliable determination of tumor volume, as well as changes in further, important follow-up markers, by means of contrast kinetics, vascular permeabilitiy and extracellular volume fraction. Thus, CAD systems enable valid assessment of early treatment response under neoadjuvant chemotherapy.

                  2222.     Studying Breast Tumour Heterogeneity with a Fractal Analysis Tool, a Prognostic Indicator of Tumour Pathological Response Before Chemotherapy Treatment

Pierluigi Di Giovanni¹, Scott IK Semple², Roger T. Staff¹, Thomas W. Redpath¹, Fiona J. Gilbert¹

¹Radiology, University of Aberdeen, Aberdeen, Scotland, UK; ²Medical Physics, University of Edinburgh, Edinburgh, Scotland, UK

Maps of the distribution of contrast agent within breast tumours can be produced by subtracting pre and post Gd-DTPA images. This subtraction map can be used for tumour heterogeneity analysis based on a fractal method. The aim of this study is to investigate whether the fractal information could provide any prognostic value in terms of tumour's pathological response. We have shown that there is a significant correlation with the tumour's pathological response and the goodness of fit of a breast tumour contrast distribution map into the fractal model (p < 0.01, Spearman’s rho = 0.42)

                  2223.     Parametric Response Mapping: A Voxel-Based Analysis of Quantitative Diffusion MRI Changes for Individualized Assessment of Primary Breast Cancer Response to Therapy

Chuck Meyer¹, Thomas Chenevert, Craig Galban, Timothy Johnson, Daniel Hamstra, Alnawaz Rehemtulla, Brian Ross

¹University of Michigan, Ann Arbor, MI, USA

This paper presents preliminary evidence supporting feasibility of using three ADC MRI interval acquisitions, two pre- and one post-therapy initiation to determine response to neoadjuvant chemotherapy within two weeks. This was a double blinded study where the clinical oncologist’s clinical assessment of response to the first cycle of chemotherapy was compared to quantitative estimates of increased intra-tumoral diffusion. The use of parametric response mapping (PRM), a voxel-by-voxel change analysis, demonstrated 100% accuracy in the initial feasibility study of 5 primary breast cancer patients.

                  2224.     Multisequence and Multiplanar Whole Body MRI for Detection of Cancer Metastases

Jingfei Ma¹, Colleen Costelloe², John Madewell², Gabriel Hortobagyi³, Marjorie Green³, Guang Cao⁴, Fei Sun⁴, Vikas Kundra²

¹Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX, USA; ²Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; ³Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; ⁴GE Healthcare, China

Scan time consideration and large FOV requirement for whole body (WB) imaging have precluded most previous WBMRI approaches from acquiring images with a large number of sequences and in different imaging planes. This can seriously affect reading confidence and lower diagnostic accuracy. In this study, we propose to use two fast Dixon sequences and a STIR-prepared diffusion weighted sequence for WB imaging. In 24 cancer patients, we demonstrate that a complete WBMRI including T2-weighted, T1-weighted (pre and post contrast injection), and diffusion-weighted imaging can be performed within approximately 1-hour on a commercially available 1.5 Tesla scanner.

                  2225.     Contrast-Enhanced Magnetic Resonance Mammography for Screening of the Controlateral Breast in Patients with Diagnosed Breast Cancer

Federica Pediconi¹, Sabrina Cagioli², Valeria Dominelli³, Maria Laura Luciani², Valeria Martino², Carlo Catalano⁴, Roberto Passariello⁵

¹Dept. of Radiological Sciences, La Sapienza University of Rome, Rome, Italy; ²of Radiological Sciences, La Sapienza University of Rome, Rome, Italy, Italy; ³of  Radiological Sciences, La Sapienza University of Rome, Rome, Italy, Italy; ⁴of Radiological Sciences, La sapienza University of Rome, Rome, Italy, Italy; ⁵of Radiological Sviences, La Sapienza University of Rome, Rome, Italy, Italy

118 patients with proven unilateral breast cancer and negative controlateral breast at physical examination, US and x-ray mammography underwent CE-MRM to evaluate the controlateral breast. Axial 3D T1-W GRE images were acquired before and after gadobenate dimeglumine injection. Images were evaluated by two readers in consensus and compared with histological findings. CE-MRM depicted lesions in the controlateral breast in 28/118 patients. Malignancy was confirmed for 22 lesions. This study demonstrates the need to carefully evaluate the controlateral breast in patients with known unilateral breast cancer.

                  2226.     A Capillary Input Function for Pharmacokinetic Analysis of DCE-MRI Breast Cancer Curves

William Kieron Lloyd¹, Thomas W. Redpath¹, Trevor S. Ahearn¹, Scott I. K. Semple², Fiona J. Gilbert¹

¹Radiology, University of Aberdeen, Aberdeen, Aberdeenshire, UK; ²Medical Physics, University of Edinburgh, Edinburgh, UK

Compartmental modelling is a common method of analysis of breast tumour that requires an estimation of the amount of contrast agent the compartment supplying the tumour. Current methods of estimating this input function do not take into account tumour heterogeneity. Using T2*-weighted images of the first pass of a contrast agent bolus through a tumour, we define localised capillary input functions (CIF). The CIF may be able to return more meaningful parameter values in the compartmental model, as variability in contrast agent delivery is a significant source of uncertainty in the method.

                  2227.     Breast Tumour DCE-MRI in Presence of B1 Inhomogeneity, Effect on K^trans/v_e Using T1-Weighted FLASH

Pierluigi Di Giovanni¹, Che A. Azlan¹, Thomas W. Redpath¹, Trevor S. Ahearn¹, Scott IK Semple², Fiona J. Gilbert¹

¹Radiology, University of Aberdeen, Aberdeen, Scotland, UK; ²Medical Physics, University of Edinburgh, Edinburgh, Scotland, UK

Breast tumour imaging with DCE-MRI and T1W FLASH at 3T is corrupted by B1 inhomogeneities across the field of view. We investigate, by simulation, how pharmacokinetic parameters K^trans and v_e are affected by B1 error. We show that K^trans and v_e can be overestimated or underestimated depending on whether the effective flip angle is higher or lower than its nominal value. We also show that the greater the values of K^trans and/or v_e the greater sensitivity to B1 inhomogeneity. Pharmacokinetic parameter errors can be avoided using a sequence less sensitive to B1 inhomogeneity or corrected using by B1 maps.

                  2228.     Quantifying Changes in Breast Tumour K^trans/v_e Parameters When Reducing Temporal Resolution of Contrast Enhanced Dynamic MRI

Pierluigi Di Giovanni¹, Thomas W. Redpath¹, Scott IK Semple², Trevor S. Ahearn¹, Fiona J. Gilbert¹

¹Radiology, University of Aberdeen, Aberdeen, Scotland, UK; ²Medical Physics, University of Edinburgh, Edinburgh, Scotland, UK

The trade off between spatial and temporal resolution plays an important role in DCE-MRI of the breast, especially when quantitative pharmacokinetic parameters are extracted. We show that K^trans is underestimated and v_e remains constant when the imaging temporal resolution is reduced. The error in K^trans increases with a reduction in temporal resolution. Our work suggests that it may be possible to decrease the temporal resolution of a dynamic scan to 20 seconds and still maintain robust estimation of pharmacokinetic parameters. This in turn may allow higher spatial resolution images to be acquired.

                  2229.     Quantitative Analysis of Breast Parenchymal Patterns Using 3D Fibroglandular Tissues Segmented Based on Breast MRI

Ke Nie¹, Jeon-Hor Chen^1,2, Chieh-Chih Hsu², Hoanglong Nguyen¹, Muqing Lin¹, Tzu-Ching Shih^1,2, Dustin Newell¹, Byron Feig¹, Orhan Nalcioglu¹, Min-Ying Lydia Su¹

¹Tu & Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, USA; ²Department of Radiology, China Medical University, Taiwan

A quantitative method was applied to analyze the morphology of the fibroglandular parenchymal pattern in the breast. Two different patterns: mixed fibroglandular and fatty tissue (N=86) vs. central fibroglandular tissue surrounded by fat (N=60) were separated. The percent density was comparable between the 2 groups, but 5 morphology features show significant differences. While the percent density showed a clear age-dependence, it was not race-dependent. On the other hand, the morphology parameters showed race-dependence, but not age-dependence. The White and Hispanic women were more likely to present mixed patterns, and the Asian women were more likely to present the central pattern.

                  2230.     Comparison of Breast Density in the Contralateral Normal Breast of Patients with Different Types of Breast Cancer Measured on MRI

Jeon-Hor Chen^1,2, F-T Hsu², H-N Shih², C-C Hsu², Daniel Chang¹, K Nie¹, O Nalcioglu¹, M-Y Su¹

¹Center for Functional Onco-Imaging, University of California Irvine, Irvine, CA, USA; ²Department of Radiology, China Medical University Hospital, Taichung, Taiwan

In this study we measured MR-based breast density in patients with IDC and DCIS, also between patients with ER-positive and ER-negative cancer and investigated whether they show significant differences. IDC and DCIS did not showed any significant difference in the breast density, suggesting that density alone might not predict differential risk for patients who will develop IDC vs. DCIS. Breast density between ER-positive and ER-negative patients was also not significantly different, suggesting the link between breast density and breast cancer may be due to factors other than or in addition to estrogen exposure.

                  2231.     Functional Connectivity and Arterial Spin Labeling in Chemotherapy Induced Cognitive Impairment ("Chemobrain")

Peter S. LaViolette¹, William Collier², Kathleen M. Schmainda^1,3, L Piacentine⁴, K L. Douville⁴, C R. Chitambar⁵, A Tran², S A. Claesges⁴, S J. Durgerian⁶, Alan S. Bloom^2,7

¹Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA; ²Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA; ³Radiology, Medical College of Wisconsin, Milwaukee, WI, USA; ⁴Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; ⁵Neoplastic Diseases and Hematology, Medical College of Wisconsin, Milwaukee, WI, USA; ⁶Neurology, Medical College of Wisconsin, Milwaukee, WI, USA; ⁷Psychiatry, Medical College of Wisconsin, Milwaukee, WI, USA

Systemic chemotherapy for breast and other cancers induces cognitive impairment in a significant proportion of patients who receive it. Often referred to as “chemobrain”, it is a common neurological deficit defined by a cohort of symptoms measurable through neuro-psychological testing. However, there are no quantitative brain imaging methods for measuring it functionally, and consequently no imaging methods to evaluate treatments that may improve function. This study uses functional connectivity and arterial spin labeling to serve this need, and measures connectivity changes between essential nodes of memory and attentional networks, and changes in cerebral blood flow in associated regions.

                  2232.     Optimization of Registration of Parametric Gd-DTPA MR with Parametric F-18-FDG PET/CT Images for Improved Breast Cancer Detection

Andrzej Krol¹, Alphonso Magri², David Feiglin, Gwen Tillapaugh-Fay, Wendy McGraw³, Edward Lipson², James Mandel⁴, Wei Lee

¹Department of Radiology, SUNY Upstate Medical University, Syracuse, NY, USA; ²Physics, Syracuse University, Syracuse, NY, USA; ³Central New York PET, Syracuse, NY, USA; ⁴Civil and Environmental Engineering, Syracuse University, Syracuse, NY, USA

We searched for the best method for registration of parametric Gd-DTPA MR with F-18-FDG PET/CT images for improved breast cancer detection. Two strategies of registration of MR and PET parametric images were considered: intensity based using free-form deformation (FFD) and geometry based using finite element method (FEM) with fiducial skin markers placed on patients’ breasts and visible in MR and PET imaging. The FFD registration was performed via CT images that were obtained during PET/CT scans. We conclude that FFD should be used for nonrigid registration of parametric MR to parametric PET breast images via CT images.

                  2233.     Comparison of Gleason Scores and MR Spectroscopic Imaging in Prostate Cancer Patients

Nagarajan Rajakumar¹, Ana Maria Gomez¹, Daniel Margolis¹, Steven S. Raman¹, Timothy McClure¹, Michael Albert Thomas¹

¹Radiological Sciences, UCLA, Los Angeles, CA, USA
Proton magnetic resonance spectroscopic imaging (MRSI) is a promising method for detecting prostate carcinomas showing higher choline and reduced citrate levels in comparison with healthy prostate tissues. 28 prostate cancer patients with different Gleason score is derived from robotic-assisted prostatectomy (GS) underwent endorectal MRSI.There was a significant difference between the (Cho+Cr)/Cit ratio of groups with four different GS (3+3, 3+4, 4+3, 4+4). Low GS shows decreased citrate where as high GS have further decreased or absent citrate and increasing choline. This pilot work demonstrates that changes in relative metabolite levels provided by MRSI can be a non invasive indicator of grade of malignancy.

                  2234.     Value of Multiparametric MRI in Prostate Cancer.

Anja Maria Weidner¹, Henrik J. Michaely¹, Andreas Lemke², Lutz Breitinger³, Maurice S. Michel⁴, Frederik Wenz⁵, Natascha Schnitzer¹, Stefan O. Schönberg¹, Dietmar Jörg Dinter¹

¹Department of Clinical Radiology and Nuclear Medicine, University Medical Center, Mannheim, Germany; ²Computer Assisted Clinical Medicine, University Medical Center, Mannheim, Germany; ^{3 4}Department of Urology, University Medical Center, Mannheim, Germany; ⁵Department of Radiation Oncology, University Medical Center, Mannheim, Germany

MRI of the prostate using T2, DWI, DCE and MRS allows in a combined approach to reliably detect and stage prostate cancer. Particularly fusion of T2 and DWI seems to be helpful for screening with a high negative predictive value.

                  2235.     DCE of the Prostate:Contrast Enhancement Correlates to Glandular Lumen

Tryggve Holck Storaas¹, Kjell-Inge Gjesdal², Jonn-Terje Geitung³, Aud Svindland⁴

¹Diagnostic physics/ Radiology, Ullevaal Universityhospital, Oslo, Norway; ²Sunnmøre MR-klinikk, Ålesund, Norway; ³Radiology, Haraldsplass University Hospital, Oslo, Norway; ⁴Pathology, Aker Universityhospital, Oslo, Norway

The heterogenous nature of prostatic tissues has been shown to give rise to two distinguishable signal components, probably attributable to secretions in acini lumen and cellular tissue. As glandular lumen is generally not available to extracellular contrast agents, the slow proton exchange may reduce signal enhancement compared to what is predicted by the fast exchange model. In this paper DCE MRI is compared to quantitative histology, and a negative correlation between the volume fraction of glandular lumen and signal enhancement is demonstrated.

                  2236.     Proton and Sodium MR Imaging of Prostate Using a Dual-Tuned Endorectal Coil at 3 T

Kyongtae Ty Bae^1,2, Chan Hong Moon¹, George J. Misic³, Jung-Hwan Kim¹, Sung-Hong Park^1,2, Tiejun Zhao⁴

¹Radiology, University of Pittsburgh, Pittsburgh, PA, USA; ²Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; ³MR SBU, MEDRAD, Inc., Indianola, PA, USA; ⁴MR Research Support, Siemens Healthcare, Pittsburgh, PA, USA

We have demonstrated the feasibility of 1H and Na23 imaging of prostate using a dual-tuned endorectal coil. Our imaging technique was tested on a phantom and prostatectomy specimens from patients with prostate cancer. Continued improvement of this technique may facilitate the improved diagnosis of prostate cancer.

                  2237.     Alignment of Digitized Whole-Mount Histopathology Slides to Prostate MR Images

Susan M. Noworolski^1,2, Richard F. Guo³, Galen D. Reed¹, Kyle Kuchinsky⁴, Kirsten Greene⁵, Peter Carroll⁵, Daniel B. Vigneron^1,2, John Kurhanewicz^1,2, Jeffry Simko⁴

¹Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA; ²Graduate Group in Bioengineering, University of California, San Francisco & Berkeley, San Francisco & Berkeley, CA, USA; ³Electrical Engineering, University of California, Berkeley, Berkeley, CA, USA; ⁴Pathology, University of California, San Francisco, San Francisco, CA, USA; ⁵Urology, University of California, San Francisco, San Francisco, CA, USA

Correlation of MR images to histopathology, the gold-standard for tissue identification, is important for evaluating MR's role in diagnosis. Digitized, whole-mount histopathology slides of the prostates of ten patients were aligned to MR images. The %overlap with only rigid alignment was 65±6% which increased to 99±0.6% after automatic deformation. Visually identified landmarks were 2.5±1.5 mm distant on average, but ranged as far as 8mm. Non-rigid alignment can greatly improve correlation of MR data to histopathology but nonuniform deformation of the prostate may remain and needs to be considered before using the aligned histopathology to classify tissue types on MRI.

                  2238.     High-B-Value Diffusion-Weighted Imaging at 3T for Detection of Prostate Cancer

Yoshimitsu OHGIYA¹, Takashi HASHIZUME¹, Junpei SUYAMA¹, Noritaka SEINO¹, Syu TAKAYA¹, Masaaki KAWAHARA¹, Makoto SAIKI¹, Masanori HIROSE¹, Takehiko GOKAN¹

¹Department of Radiology, Showa University School of Medicine, Tokyo, Japan

PURPOSE: To investigate usefulness of high-b-value DWI for detection of prostate cancer.

                  2239.     High Spatial and Spectral Resolution (HiSS) MRI of the Prostate: A Pilot Study

Milica Medved¹, Aytekin Oto¹, Gregory S. Karczmar¹

¹Radiology, University of Chicago, Chicago, IL, USA

Reliable navigation of prostate biopsy cores is necessary to improve accuracy. High spatial and spectral resolution (HiSS) imaging provides high-quality morphologic images and spectrally resolved water resonance in each voxel. Detailed shape of the water resonance is sensitive to perfusion, hypoxia, certain protein deposits, etc. and could in principle visualize cancerous tissue. We report HiSS MR imaging of human prostate in five healthy volunteers. Morphologic images derived from HiSS data show better fat suppression and higher anatomic detail, compared to clinical fast spin echo images. In healthy volunteers, there was no observable structure to the water resonance.

                  2240.     3T DCE MRI in Prostate Cancer – Comparison Between Population Average and Patient Specific Arterial Input Function

Ran Meng¹, Burkhard Meadler², Silvia D. Chang³, Edward C. Jones⁴, S Larry Goldenberg^5,6, Piotr Kozlowski^1,6

¹UBC MRI Research Centre, Vancouver, BC, Canada; ²Philips Healthcare, Vancouver, BC, Canada; ³Radiology, University of British Columbia, Vancouver, BC, Canada; ⁴Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; ⁵Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; ⁶The Prostate Centre at VGH, Vancouver, BC, Canada

We compared the quality of fit to the extended Kety model of the prostate DCE MRI data (acquired with 3T clinical scanner from two patients) using population-averaged and patient specific Arterial Input Function (AIF). Kinetic parameters (Ktrans, ve, and vp) were calculated from tumor, peripheral zone and central gland. By comparing Chi2 of the fit with the two AIFs of a high enhancing voxel, we conclude that patient specific AIF provides more accurate pharmacokinetic modeling of prostate DCE MRI data in high enhancing areas than population-averaged AIF, thus patient specific AIF may result in more accurate detection of prostatic carcinoma.

                  2241.     MR-Histology Correlation in Ex-Vivo Human Prostate Specimens

Simon Yoon Kimm¹, Jin Hyung Lee², Dwight G. Nishimura², Tatum V. Tarin¹, Bob S. Hu², Kristen Jensen³, James D. Brooks¹

¹Department of Urology, Stanford University, Palo Alto, CA, USA; ²Department of Electrical Engineering, Stanford University, Palo Alto, CA, USA; ³Department of Pathology, Stanford University, Palo Alto, CA, USA

Accurate correlation can be achieved between MR imaging, gross anatomic sections, and histologic sections in human prostatectomy specimens using a combination of injected acrylic paint fiducials, plane-finding device, and standard tissue processing.

                  2242.     Utility of Quantitative T2 Signal Intensity and ADC Measurements in Differentiating Prostate Cancer from Post-Biopsy Hemorrhage

Andrew Rosenkrantz¹, Martin Kopec¹, Xiangtian Kong², Jonathan Melamed², Bachir Taouli¹

¹Radiology, NYU Medical Center, New York, NY, USA; ²Pathology, NYU Medical Center, New York, NY, USA

The objective of our study was to assess the value of quantitative T2 and ADC measurements for the differentiation of benign peripheral zone (PZ), tumor and hemorrhagic foci in patients with prostate cancer before prostatectomy. We measured relative T2 SI (signal intensity) normalized to muscle SI ("rT2") and ADC in benign non-hemorrhagic PZ, benign hemorrhagic foci, and tumor foci in 13 patients. Tumor foci showed significantly lower rT2 and ADC than did hemorrhagic and non-hemorrhagic benign PZ, rT2 and ADC were not significantly different between hemorrhagic and non-hemorrhagic benign PZ. These preliminary findings support quantitative T2 and ADC measurement for differentiating tumor from hemorrhage.

                  2243.     Assessment of Registration Accuracy Between Magnetic Resonance Imaging and Three Dimensional Trans-Rectal Ultrasound Imaging of Prostate Cancer

Elmer Soto¹, Vaishali Karnik^1,2, Igor Gyacskov², Lori Gardi², Tamie L. Poepping^3,4, Gord John Campbell^4,5, Aaron Fenster^1,2, Charles Alexander McKenzie^1,4

¹Biomedical Engineering Graduate Program, The University of Western Ontario, London, Ontario, Canada; ²Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada; ³Physics & Astronomy, The University of Western Ontario, London, Ontario, Canada; ⁴Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada; ⁵Industrial Materials Institute - London, National Research Council Canada, London, Ontario, Canada

Trans-rectal ultrasound (TRUS) guided biopsies often underestimate or fail to detect the presence of prostate cancer (PCa). Fused MRI and 3D TRUS images have the potential to dramatically reduce the false negative rate of TRUS-guided biopsies. To validate the accu-racy of registering MR images to 3D TRUS images, a polyvinyl alcohol prostate phantom was constructed. MRI and TRUS images of the phantom were segmented and registered. The fiducial localization error and target registration error between corresponding mark-ers in the phantom was sufficiently small to suggest that our technique is accurate enough to guide prostate biopsies.

                  2244.     A Voxel-By-Voxel Benchmark Comparison Between Two in Vivo Prostate MRSI Techniques

Niranjan Venugopal^1,2, Boyd McCurdy^2,3, Salem Al Mehairi⁴, Abdulaziz Alamri⁴, Gurdarshan Singh Sandhu⁴, Darrel Drachenberg⁴, Lawrence Ryner^1,2

¹National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada; ²Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba, Canada; ³Department of Medical Physics, CancerCare Manitoba, Winnipeg, Manitoba; ⁴Department of Surgery (Section of Urology), University of Manitoba, Winnipeg, Manitoba, Canada

The effective suppression of periprostatic lipid signal to reduce contamination artifacts is vital to obtaining good spectroscopic data from in vivo prostate MRSI. We compare the commercially available PRESS based 3D MRSI technique to our modified PRESS 3D MRSI technique. Our modified sequence includes the first application of conformal voxel magnetic resonance spectroscopy (CV-MRS) optimization to in vivo prostate MRSI. This method “conforms” the excitation voxel to the shape of the prostate, effectively nulling signal from periprostatic lipids. A voxel-by-voxel benchmark test reveals that ~40% more spectra of are acceptable quality using the CV-MRS technique, and that in general the quality of the spectra throughout the prostate is improved.

                  2245.     Combined Prostate DTI and DCE MRI at 3T – Correlation with Biopsy

Piotr Kozlowski¹, Ran Meng², Burkhard Meadler³, Silvia D. Chang⁴, Edward C. Jones⁵, S Larry Goldenberg⁶

¹The Prostate Centre at VGH, Vancouver, BC, Canada; ²UBC MRI Research Centre, Vancouver, BC, Canada; ³Philips Healthcare, Vancouver, BC, Canada; ⁴Radiology, University of British Columbia, Vancouver, BC, Canada; ⁵Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; ⁶Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

DTI and DCE MRI were carried out in 18 prostate cancer patients. Mean diffusivity, fractional anisotropy and pharmacokinetic modeling parameters calculated from MRI data were correlated with biopsy. All MRI parameters, with the exception of extra-cellular extra-vascular space, showed significant differences between cancer and benign prostate. Sensitivity and specificity of the DTI data were 86% and 89% respectively, and 66% and 94% for the DCE data. When both ADC and DCE results were combined the sensitivity increased to 91% while specificity lowered to 85%. Combined DTI and DCE MRI provide better prostate cancer diagnosis than each technique alone.

                  2246.     Independent Component Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Images of Prostate Tumours

Tong San Koh¹, Choon Hua Thng², Septian Hartono^1,2, David Collins³, Sophie Richards³, Martin O. Leach³, Aslam Sohaib⁴, David Dearnaley³, Dow-Mu Koh³

¹School of Electrical & Electronic Engineering, Nanyang Technological University, Singapore, Singapore; ²Department of Oncologic Imaging, National Cancer Centre Singapore, Singapore, Singapore; ³Institute of Cancer Research, Sutton, Surrey, UK; ⁴Department of Radiology, Royal Marsden Hospital, Sutton, Surrey, UK

We aim to extract tumour component maps using Independent Component Analysis (ICA) statistical technique from prostate DCE MRI datasets corresponding to a washout enhancement behaviour for comparison with histology. Five prostate DCE MRI cases with histology comparison were processed with ICA. It is found that ICA extracts spatial component maps corresponding to a few consistent enhancement profiles within the prostate DCE MRI datasets. ICA identifies voxels within the prostate that are associated with a washout signal-time profile which correlated with tumour locations on histology.

                  2247.     MRI/TRUS Fusion for Prostate Biopsy: Early Results and Clinical Feasibility

Ramkrishnan Narayanan¹, John Kurhanewicz², Katsuto Shinohara², David Crawford³, Albaha Barqawi³, Anne Simoneau⁴, Jasjit Suri¹

¹Engineering, Eigen Inc., Grass Valley, CA, USA; ²University of California, San Francisco, CA, USA; ³University of Colorado, Denver, CO, USA; ⁴University of California, Irvine, CA, USA

Conventional ultrasound imaging guided biopsy cannot detect prostate cancer with sufficient sensitivity, and up to 40% of prostate cancers are iso-echoic. T2-weighted magnetic resonance imaging using endorectal coil combined with pelvic phased-array coil provides high resolution images of the prostate with high sensitivity of identifying cancer. A key challenge in using MRI with ultrasound for improving prostate biopsy procedures is their registration. We describe our preliminary registration experiment using two multimodality phantoms with six and twelve glass beads embedded (fiducials). Preoperative MRI and ultrasound are registered using a nonlinear deformation model, and registration error is reported.

                  2248.     A Comparison of Arterial Input Functions Derived from Phase and Magnitude for Quantitative DCE-MRI of the Prostate

Greg O. Cron¹, Claire Foottit², Thomas E. Yankeelov³, Leonard I. Avruch⁴, Ian Cameron^1,4

¹Ottawa Health Research Institute, Ottawa, Ontario, Canada; ²Carleton University, Ottawa, Ontario, Canada; ³Vanderbilt University Institute of Imaging Science, Nashville, TN, USA; ⁴The Ottawa Hospital, Ottawa, Ontario, Canada

For quantitative DCE-MRI of prostate tumors, conventional magnitude-derived arterial input functions (AIFs) may be confounded by flow, T2*, and saturation effects. Previous studies have suggested that measuring changes in phase may be superior to magnitude for estimating the AIF. In this study, phase-derived AIFs were compared to magnitude-derived AIFs by computing Ktrans and ve in a reference tissue (obturator internus muscle, n=9 patients). Phase-derived AIFs resulted in 15% less patient-to-patient variation in computed values of Ktrans and 66% less variation in ve. It is therefore expected that phase-derived AIFs will provide more consistent perfusion measurements in prostate tumors.

                  2249.     Correlation of MR Imaging Guided Prostate Biopsy Determined Gleason Grade and True Gleason Grade in Radical Prostatectomy Specimens

Caroline Hoeks¹, Thomas Hambrock¹, Diederik Somford², Jurgen Futterer¹, Christina Hulsbergen-van de Kaa³, Inge van Oort², Alfred Witjes², Jelle Barentsz¹

¹Radiology, Radboud University Medical Centre, Nijmegen, Gelderland, Netherlands; ²Urology, Radboud University Medical Centre; ³Pathology, Radboud University Medical Centre, Nijmegen, Netherlands

Problem: Transrectal ultrasound guided biopsy (TRUS-GB) Gleason score (GS) incorrectly estimates true prostatectomy GS.

                  2250.     MR Diffusion-Weighted Imaging in Prostate Cancer:A Valuable Tool for MR-Guided Biopsy?

Matthias C. Roethke¹, Matthias P. Lichy², Alexander Pelzer³, Claus H. vonWeyhern⁴, David Schilling⁵, Claus D. Claussen⁶, Heinz P. Schlemmer⁷

¹Dep. of Diagnostic Radiology, University Tuebingen, Tuebingen, Germany; ²Dep. of Diagnostic Radiology, University Tuebingen, Germany; ³Dep. of Urology, Tuebingen University, Germany; ⁴Dep. of Pathology, Tuebingen University, Germany; ⁵Dep. of Urology, Germany; ⁶Dep. of Diagnostic Radiology, Tuebingen University, Germany; ⁷Dep. of Diagnostic Radiology, Tuebingen University, Tuebingen, Germany

Multifocality of cancer was found in 90% of the patients on histopathologic whole mounted sections. DWI proved to be highly accurate in tumors larger than 5-10mm. Particularly DWI yielded no false positive findings and would therefore not increase the amount of negative MR-guided prostate biopsies. DWI including automatic calculation of ADC maps is fast and robust to perform and applicable within a MR guided biopsy procedure. The accuracy of DWI for tumor detection and its usability for MR-guided biopsy within one single examination could be further improved at 3.0T enabling higher spatial resolution and the application of higher b-values.

                  2251.     Multiparametric 3T MR Imaging for Detection of Prostate Cancer with Surgical Correlation

Baris Turkbey¹, Haresh Mani², Marcelino Bernardo¹, Yuxi Pang³, Kiranpreet Khurana⁴, Paul Albert⁵, Peter Pinto⁴, Maria Merino², Peter L. Choyke¹

¹Molecular Imaging Program, NCI, NIH, Bethesda, MD, USA; ²Laboratory of Pathology, NCI, NIH, Bethesda, MD, USA; ³Philips Healthcare, Bethesda, MD, USA; ⁴Urologic Oncology Branch, NCI, NIH, Bethesda, MD, USA; ⁵Biometric Research Branch, Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD, USA

While 3T endorectal MRI of prostate reveals comparable sensitivity and specificity to those reported for 1.5T the combined use of multiparametric MRI (DCE-MRI and MR spectroscopy) improves the positive predictive value for tumor detection.

                  2252.     Correlation of Endorectal 2D JPRESS Findings with Pathological Gleason Scores in Prostate Cancer Patients

Nagarajan Rajakumar¹, Daniel Margolis¹, Steven S. Raman¹, Ana Maria Gomez¹, Timothy McClure¹, Nader Binesh², Michael Albert Thomas¹

¹Radiological Sciences, UCLA, Los Angeles, CA, USA; ²MRI, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and the second leading cause of cancer deaths in American men. To determine if the metabolite ratios of choline plus creatine to citrate and choline plus creatine to spermine in patients with two ranges of pathological Gleason scores, namely (3+4) and (4+3) can be calculated using the localized two-dimensional (2D) J-resolved spectroscopy (JPRESS) and correlated with prostate cancer aggressiveness. Our pilot study suggests that 2D JPRESS can be reliably evaluated in a clinical setting using an endorectal coil, and good correlation between the metabolite ratios and the pathology based Gleason scores.

                  2253.     Feasibility of Chemical Exchange Saturation Transfer (CEST) MRI for Prostate Cancer Detection at 3T

Guang Jia¹, Jinyuan Zhou², Seongjin Choi¹, Wenbo Wei¹, Steffen Sammet¹, Jiachao Liang¹, Jun Zhang¹, Zarine K. Shah¹, Mitva Patel¹, Ronney Abaza³, Pankaj Dangle³, Douglas Martin⁴, Michael V. Knopp¹

¹Department of Radiology, The Ohio State University, Columbus, OH, USA; ²Department of Radiology, Johns Hopkins University, Baltimore, MD, USA; ³Center for Robotic and Computer Assisted Surgery, The Ohio State University, Columbus, OH, USA; ⁴Department of Radiation Medicine, The Ohio State University, Columbus, OH, USA

This study is to evaluate whether CEST MRI is feasible to image prostate cancer patients for tumor detection. All subjects were imaged in a 3 Tesla MR system (Achieva, Philips) using an 8-channel SENSE Torso coil or 32-channel SENSE Torso/Cardiac coil. MT-spectrum of the prostate cancer regions revealed asymmetric water saturation profile with higher MTR at negative frequency offsets, which gave larger MTR_asym (3.5ppm) in tumor regions than normal PZ and CG. This feasibility study provides a diagnostic potential of CEST MRI for tissue characterization in prostate cancer screening and lesion detection.

                  2254.     Correlation Between 3T MRI Apparent Diffusion Coefficient Values and Prostate Cancer Gleason Score in Prostatectomy Specimens

Caroline Hoeks¹, Thomas Hambrock¹, Diederik Somford², Henk-Jan Huisman¹, Christina Hulsbergen-van de Kaa³, Inge van Oort², Alfred Witjes², Jelle Barentsz¹

¹Radiology, Radboud University Medical Centre, Nijmegen, Gelderland, Netherlands; ²Urology, Radboud University Medical Centre; ³Pathology, Radboud University Medical Centre

Problem: Cellular densities in human cancers correlate to Apparent Diffusion Coefficient (ADC) values.

                  2255.     Retrospective Analysis of Prostate Cancer Recurrence Potential with Tissue Metabolomic Profiles

Andreas Maxeiner^1,2, Christen B. Adkins², W. Scott McDougal³, Chin Lee Wu^3,4, Leo Ling Cheng^4,5

¹Radiology and Urology, Charité Universitätsmedizin Berlin , Germany; ²Pathology , Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; ³Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; ⁴Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; ⁵Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Recognizing the lack of effective clinical protocol for the evaluation of prostate cancer (PCa) recurrence potentials after prostatectomy, this study retrospectively evaluates the ability of tissue magnetic resonance spectroscopy (MRS) metabolomic profiles to identify PCa recurrence. Sixteen PCa-recurrent cases were paired with age- and Gleason-score-matched cases without recurrence and of the same pathological stage (n=16) or clinical stage (n=16). Metabolomic profiles from statistical analyses of the 27 most common and intensive spectral and metabolic regions from clinical-stage-matched groups can identify recurrence (P < 0.008). Applying the profiles onto the pathological-stage-matched groups, the overall 73.9% accuracy in identifying recurrence was reached.

                  2256.     Optimum Spatial Resolution and Number of Averages of Diffusion Tensor Imaging in Prostate Cancer Detection

Yu-Jen Chen¹, Y-S Pu², S-C Chueh², C-T Shun³, W-C Chu¹, W-Y Isaac Tseng^4,5

¹Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan; ²Department of Urology; ³Pathology; ⁴Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; ⁵Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan

This study aimed to investigate the diagnostic performance of trace apparent diffusion coefficient maps in prostate cancer detection at different spatial resolutions and number of averages, and to determine a practical protocol that could provide satisfactory diagnostic performance for PCA detection. The tADC maps were reconstructed into 3 different isotropic resolutions, i.e. 1 mm, 2 mm and 3 mm. For each resolution there were 3 different NAV, i.e. 2, 4, and 6 averages. The diagnostic performance of tADC maps for each data set was determined by comparing with the TRUS biopsy results core by core.

                  2257.     Histologic Basis of MRI in Prostate Peripheral Zone:  Determination of the Relationships Between Sub-Cellular Components and ADC, T2, Ktrans and Ve

Deanna Lyn Langer^1,2, Theo H. van der Kwast³, Andrew J. Evans³, John Trachtenberg⁴, Brian C. Wilson⁵, Masoom A. Haider^1,2

¹Joint Department of Medical Imaging, Princess Margaret Hospital, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada; ²Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; ³Department of Pathology and Laboratory Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; ⁴Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; ⁵Medical Biophysics, University of Toronto, Ontario Cancer Institute, Toronto, Ontario, Canada

Histological correlates of ADC, T2, Ktrans and ve were investigated in the peripheral zone (PZ) of the prostate. Whole mount sections were digitized and segmented at histological-resolution. PZ-tissue in MRI and histology was radially-sectioned. The slope (m) of median parameter values versus %area of nuclei, cytoplasm, stroma, and lumen, was tested for significance. ADC, T2 and Ktrans were significantly related to %nuc (m<0: ADC, T2; m>0: Ktrans). Other significant relationships were between ADC and %cyt (m<0) and %lumen (m>0), although trends existed for T2 and Ktrans. This work elucidates some of the inherent relationships between MRI and underlying histology.

                  2258.     Correlation of Phospholipid Metabolites with the Proliferation Marker Ki-67 in Prostate Cancer Tissues

Haris Tsachres¹, Kayvan Keshari², Carissa Santos², Lynn DeLosSantos³, Laura Tabatabai⁴, Jeffry Simko⁴, Katsuto Shinohara⁵, Peter Carroll⁵, Dan Vigneron³, John Kurhanewicz³

¹Radiology, University of California San Francisco (UCSF), , San Francisco , CA, USA; ²Radiology, University of California San Francisco (UCSF), San Francisco , CA, USA; ³Radiology, University of California San Francisco (UCSF), San Francisco, CA, USA; ⁴Pathology, University of California San Francisco (UCSF), CA, USA; ⁵Urology, University of California San Francisco (UCSF), CA, USA

This study investigated the relationship between individual phospholipid metabolite concentrations, Gleason score, and rate of cellular proliferation in malignant prostatectomy samples by performing HR-MAS two-dimensional total correlation spectroscopy (TOCSY), pathology and Ki-67 staining on the same samples. High grade prostate cancers were found to have significantly higher concentrations of PC+GPC and higher Ki-67 staining than low grade (³ 3+4) prostate cancer. Similarly, low grade prostate cancers were found to have significantly higher concentrations of PC+GPC and higher Ki-67 staining than benign samples. This is of great clinical significance since most prostate cancers are indolent and will never metastasize, but it is believed that cancers with a dominant Gleason pattern 4, even of small volume, are aggressive and potentially lethal.

                  2259.     Heterogeneity of Vascular Permeability in Breast Lesions with Dynamic Contrast Enhanced MRI

Chihwa Song¹, Matthew Robert Smith¹, Yin Huang¹, Robert Jeraj¹, Sean Fain^1,2

¹Department of Medical Physics, University of Wisconsin, Madison, WI, USA; ²Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA

We performed compartment modeling using Tofts’ model. Mean vascular permeability over lesions has been generally used to characterize tumors. However, tumors are known to be heterogeneous. Thus, we utilized spatial statistics and an iterative erosion method to study spatial characteristics of kinetic parameters. Results showed that vascular permeability was higher in the interior than in the periphery and the difference in permeability was larger in benign than in malignant lesions. It was also found that malignant lesions were more heterogeneous than benign lesions. Classification performance of the metrics we examined was found to be better than that of mean permeability over lesions.

                  2260.     Adaptive Clustering of MR Diffusion Parameter Space for Brain Tumor Tissue Characterization

Priya Goel¹, Matthias Karrasch², Jan A. den Hollander³, James Macdowell Markert⁴, Louis Burt Nabors⁵, Narsimha Shastry Akella¹

¹Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA; ²Clinical Research and Development, MediGene AG, Munich, Germany; ³Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA; ⁴Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL; ⁵Neurology, The University of Alabama at Birmingham, Birmingham, AL, USA

Quantitative assessment of malignant brain tumor therapy response remains challenging due to limited in-vivo biomarkers that can differentiate infiltrative tumor from healthy brain tissue. Diffusion Tensor Imaging derived isotropy "p" and anisotropy "q" maps were plotted on a 2D feature space and partitioned to characterize constituent tissue using an adaptive fuzzy clustering algorithm. The resulting segmentation permits longitudinal assessment of early and subtle white matter changes around the tumor and quantitative analyses which is useful in therapy efficacy evaluation.

                  2261.     Integration of 3.0T MRI Into a Radiation Oncology Department: Initial Experience

William H. Hinson¹, Traci E. Ball¹, Wendy M. Dolesh¹, Laila F. Graham¹, Edward G. Shaw¹, J. Daniel Bourland¹, William T. Kearns¹, Michael T. Munley¹, Allan F. deGuzman¹

¹Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

This study presents our initial experience with the installation of a 3.0T MR system into a Radiation Oncology Department. The work discusses the benefits and issues of multi-modality treatment planning. Proper safety training for the Radiation Oncology is an important part of the integration.

                  2262.     Non-Enhancing Pixels: A Specific Additional DCE-MRI Kinetic Parameter for Assessing Antivascular Effects of Anti-Angiogenic and Vascular Disruptive Agents

N. Jane Taylor¹, Nina Tunariu², J James Stirling¹, David J. Collins², Paul Nathan³, James A. d'Arcy², Mei-Lin W. Ah-See, Andreas Makris, Ian Judson⁴, Martin O. Leach², Dow-Mu Koh², Anwar R. Padhani¹

¹Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK; ²CR-UK Clinical MR Research Group, Royal Marsden Hospital, Sutton, Surrey, SM2 5PT, UK; ³Oncology Dept, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK; ⁴Phase I Clinical Trials Unit, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK

An evaluation of whether non-enhancing (NE) pixels should be included in DCE-MRI analyses of therapy response was performed, by comparing data from a breast cancer cohort receiving chemotherapy with a phase I cohort of mixed solid tumours receiving a combination of vascular disruptive and antiangiogenic agents. Our analysis shows that increasing numbers of NE pixels is a

                  2263.     Rectal Cancer Staging with High-Resolution 3D Imaging Sequences

Tobias Baumann¹, Markus Treier¹, Axel zur Hausen², Matthias Langer¹, Arnd-Oliver Schäfer¹

¹Department of Diagnostic Radiology, University Hospital Freiburg, Freiburg, Germany; ²Department of Pathology, University Hospital Freiburg, Freiburg, Germany

Circumferential resection margin (CRM), T-stage and nodal stage are the most important factors influencing therapy and outcome in rectal cancer, but the optimal imaging protocol to accurately assess these image features is yet under debate. In this study we therefore sought to evaluate thin-slice, high-resolution pelvic MRI with 3D sequences with a focus on detection of nodal disease and the diagnostic value of contrast enhanced imaging. T-staging strongly depended on reader experience and prior neoadjuvant therapy reduced the accuracy of MRI. A combination of morphologic criteria from T2 and contrast enhanced sequences yielded the highest accuracy for nodal staging.

                  2264.     Investigation of a Logistic Model for T2* Dynamic Susceptibility Weighted (DscMRI) Perfusion Studies

Graeme M. Wardlaw^1,2, Raimond Wong³, Colm Boylan⁴, Ryan Rebello⁴, Michael D. Noseworthy^2,5

¹Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, Canada; ²Brain-Body Institute, St. Josephs Healthcare, Hamilton, ON, Canada; ³Dept. of Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada; ⁴Dept. of Diagnostic Imaging, St. Josephs Healthcare, Hamilton, ON, Canada; ⁵Electrical and Computer Engineering, School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada

Investigation of tumour microvasculature typically involves application of dynamic contrast methods, exploiting T1 or T2 based relaxation. However, typical pharacokinetic models simplify complex biological systems via numerous assumptions. Alternatively, model-free approaches offer an easy, and potentially equally effective means of assessing tissue microstructure. Herein, we investigate a 6-parameter logistic approach applied to a T2*-weighted echo-planar imaging readout bolus response curve. This allows for increased spatial coverage over T1 methods, while maintaining rapid 1.5s temporal acquisition. Initial investigation of rectal cancer shows good clinical and previous study correlation.

                  2265.     The Implication of Assuming a Linear Relationship Between MR Signal and Contrast Agent Concentration for Evaluating the Drug Effects for DCE-MRI

Poe-Jou Chen^1,2, A.r Gregory Sorensen¹

¹Athinoula A. Matinos Center for Biomedical Imaging, Department of Radiology, MGH, Charlestown, MA, USA; ²Nuclear Science and Engineering, Massachusetts Instituite of Technology, Cambridge, MA, USA

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive imaging technique that has the ability to study tumor vascular functions. It has been widely used for a range of clinical oncologic applications including cancer detection, grading, and evaluation of therapeutic response. A number of pharmacokinetic models have been proposed to characterize the signal intensity curve and associate it with the physiological condition in tumors. One of the distinct elements of pharmacokinetic modeling is the requirement of the time course of contrast agent concentration. However, a nonlinear relationship exists between the MR signal and contrast agent concentration for the most used spoiled gradient-echo (SPGR) pulse sequence for DCE MRI. T1 information is required for MR signal to be converted to contrast agent concentration. It is possible to assume the signal enhancement is linearly related to contrast agent concentration when and . The linear assumption is desirable since the T1 measurement is not always feasible in clinical setting. In this abstract, we will discuss the implication of this linear assumption in the regard of drug efficacy evaluation.

                  2266.     Partial Volume-Related Errors in Parameters Derived from Dynamic Contrast-Enhanced MRI – Implications for Clinical Trials

Anita Banerji¹, Yvonne Watson¹, Caleb Roberts¹, Angela Caunce¹, Giovanni A. Buonaccorsi¹, Geoff J. Parker¹

¹Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, The University of Manchester, Manchester, Greater Manchester, UK

The dual blood supply of liver tissue leads to contrast agent time courses that differ significantly from that of a tumour rim. This work uses a software phantom to quantify the influence of partial volume effects on the mean and median K^trans values of a liver tumour as it reduces in size, mimicking anticipated treatment effects. We demonstrate that median values accurately reflect tumour characteristics except at small tumour sizes where an overestimation is seen. This overestimation is greater if the tumour is located in cirrhotic liver rather than normal liver tissue.

                  2267.     Simultaneous Quantification of Heterogeneity in Multiple DCE-MRI Parameters

Chris James Rose¹, James Patrick O'Connor¹, Yvonne Watson¹, Caleb Roberts¹, Giovannni A. Buonaccorsi¹, Susan Cheung¹, Brandon Whitcher², Geoffrey J. Parker¹

¹Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, The University of Manchester, Manchester, UK; ²MRI Modelling, Clinical Imaging Centre, GlaxoSmithKline, London, UK

Dynamic contrast-enhanced MRI and tracer kinetic modelling is increasingly common in clinical trials of anti-cancer therapies, and yields voxel-wise estimates of the parameters K^trans, v_e and v_p. Most methods of quantifying the heterogeneity in DCE-MRI parameter maps—such as the commonly-applied histogram analysis—analyse parameters individually, which may neglect important relationships between the parameters. We propose a method to allow heterogeneity to be quantified by summarising the joint distribution (histogram) of model parameter values. We apply the method to clinical trial data, showing that it is highly repeatable, very quick to compute and sensitive to known drug effect.

                  2268.     The Microvascular Characteristics of Cervical Cancer: Limitations of the Modified-Tofts Tracer Kinetic Model for the Analysis of DCE-MRI Data

Stephanie B. Donaldson^1,2, Catharine M.L. West³, Susan E. Davidson⁴, Bernadette M. Carrington⁵, Gillian Hutchison⁵, Steven P. Sourbron⁶, David L. Buckley²

¹North Western Medical Physics, Christie Hospital NHS Foundation Trust, Manchester, UK; ²Imaging Science and Biomedical Engineering, University of Manchester, Manchester, UK; ³Academic Department of Radiation Oncology, University of Manchester, Manchester, UK; ⁴Department of Clinical Oncology, Christie Hospital NHS Foundation Trust, Manchester, UK; ⁵Department of Radiology, Christie Hospital NHS Foundation Trust, Manchester, UK; ⁶Josef Lissner Laboratory for Biomedical Imaging, Ludwig-Maximilian-University, Munich, Germany

The modified-Tofts tracer kinetic model is often used to analyse DCE-MRI data but its validity is dependent upon assumptions such as negligible mean transit time (MTT). We compared the modified-Tofts model with its parent model, a general 2-compartment exchange model (2CXM), using DCE-MRI data from 27 patients with cervical cancer. Fits obtained with the modified-Tofts model were poorer than those obtained with the 2CXM and comparable parameters were significantly different. MTT was non-negligible suggesting that the 2CXM is more suitable for the analysis of this DCE-MRI dataset.

                  2269.     Comparison of Perfusion Parameters in Normal and Metastatic Bone Marrow Using DCE-MRI and Pharmacokinetic Modeling: A Reference Study

Nicolas Michoux¹, Paolo Simoni¹, Bertrand Tombal², Frank Peeters¹, Xavier Banse³, Jean-Pascal Machiels⁴, Frédéric Lecouvet¹

¹Radiodiagnostic Unit, Université Catholique de Louvain, Brussels, Belgium; ²Laboratory of Cell Physiology, Université Catholique de Louvain, Brussels; ³Orthopedic Surgery, Université Catholique de Louvain, Brussels, Belgium; ⁴Oncology Unit, Université Catholique de Louvain, Brussels, Belgium

Malignant involvement of bones has significant effects on the blood supply, endothelial permeability and composition of the bone marrow, presumably altering the perfusion of the bone marrow. Therefore, the perfusion in patients with normal bone marrow and in patients with untreated bone metastases of prostate cancer was assessed using dynamic contrast-enhanced magnetic resonance imaging (spoiled 2D single-shot turbo-FLASH sequence with injection of Gd-DTPA) at 1.5T and the extended Kety model. Perfusion parameters Ktrans, ve and vp were significantly lower in healthy persons and may constitute reference values. This technique may provide useful surrogates for monitoring the response to anti-cancer therapy.

                  2270.     Comparison of DCE-MRI and DCE-CT in Bladder Cancer

Josephine Helen Naish¹, Deirdre M. McGrath², Lauren J. Baines¹, Katia Passera³, Caleb Roberts¹, Sue Cheung¹, M Ben Taylor⁴, John P. Logue⁴, David L. Buckley¹, Jean Tessier⁵, Helen Young⁵, John C. Waterton^1,5, Geoff J. Parker¹

¹Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK; ²Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, Canada; ³Dipartimento di Ingegneria Biomedica, Politecnico di Milano, Milan, Italy; ⁴Christie Hospital, Manchester, UK; ⁵AstraZeneca, Macclesfield, Cheshire, UK

DCE-MRI biomarkers are increasingly used in cancer clinical trials. DCE-CT is a widely available alternative which provides an independent measure of closely related parameters and is more robustly modelled due to the direct relationship between contrast agent concentration and signal intensity. In this study we compare parameters derived using DCE-MRI and DCE-CT in ten patients with primary bladder cancer. Median values for both Ktrans and ve were in good quantitative agreement with CoVs of 21% and 15% respectively, comparable to that typically achieved in repeat DCE-MRI studies.

                  2271.     Statistical Comparison of Tofts-Model Parameters with Descriptive and Approximated Descriptive Parameters

Hendrik Oliver Arp Laue¹, Christian M. Zechmann², Patrik Zamecnik², Horst Karl Hahn¹, Heinz-Otto Peitgen¹

¹MeVis Research, Bremen, Germany; ²Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Dedicated tracer kinetics model for DCE-MRI data are gaining importance since they allow extracting vascular tissue properties. Most of these models require extensive time for calculating parameter maps, especially with the increase of spatial and temporal resolution. These processing times are generally too long for the clinical routine. Descriptive parameters are faster and less vulnerable to optimization errors. But they lack the linkage to physiological parameters and the higher sensitivity to noise. In this work, we correlated a number of simple descriptive parameters to the parameters of the Tofts-model to identify candidates to bypass time consuming calculations.

                  2272.     Nonparametric Kinetic Analysis of DCE-MRI Images Taken from Glioblastoma Patients

Gregory Z. Ferl¹, Michel Friesenhahn², Lisa J. Bernstein², Daniel P. Barboriak³, Ruediger E. Port¹

¹Early Development PKPD, Genentech, Inc., South San Francisco, CA, USA; ²Nonclinical Biostatistics, Genentech, Inc., South San Francisco, CA, USA; ³Department of Radiology, Duke University Medical Center, Durham, NC, USA

A non-parametric method for the analysis of dynamic contrast enhanced MRI data is described here, where assumption of a particular compartmental structure is not required. Pre- and post-treatment scans taken from glioblastoma patients were analyzed, where deconvolution of the input signal (venous tracer concentration) and the output signal (tumor time activity curve) yielded the tumor impulse response function (IRF) for each scan. Area under the curve of the IRF decreases significantly one day after start of treatment. Mean residence time of the tracer molecule can also be calculated based on the IRF and is approximately constant for each patient.

                  2273.     Dynamic Contrast Enhanced Magnetic Resonance Imaging Analysis of Different Head and Neck Cancers

Kar-ho Francis Lee¹, Ann Dorothy King¹, Ka-Wai Yeung¹, Buig-yue Ma², Kwok-Hung Yu², Kunwar Bhatia¹, Anil Ahuja¹

¹Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China; ²Department of Clinical Oncology, the Chinese University of Hong Kong, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China

The aim of the study was to determine the characteristics of three head and neck cancers on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and to determine if there are any significant differences between them.

                  2274.     Semi-Parametric Analysis of Gd-DTPA Kinetics in Glioblastoma

Ruedi E. Port¹, Lu Xu¹, Lisa J. Bernstein², Timothy P. L. Roberts³, Daniel P. Barboriak⁴, Nicholas van Bruggen⁵

¹Early Development PKPD, Genentech Inc., South San Francisco, CA, USA; ²Biostatistics, Genentech Inc., South San Francisco, CA, USA; ³Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; ⁴Radiology, Duke University Medical Center, Durham, NC, USA; ⁵Biomedical Imaging, Genentech Inc., South San Francisco, CA, USA

Gd-DTPA kinetics in tissue are often described by assuming an impulse-response function (IRF) comprised of a delta function and one exponential. Kinetics in malignant tumors typically require adding a second exponential. We propose to calculate non-compartmental descriptors of the IRF within the observation period: area under the curve (AUC) and mean residence time (MRT). AUC in malignant glioblastoma is consistently reduced 24 hours after dosing of bevacizumab while MRT remains apparently unchanged. -- The proposed analysis avoids model overinterpretation and prediction beyond the time of measuring, yet enables mechanistic hypotheses generating.

                  2275.     Comparison of Perfusion-Weighted Imaging Techniques in a Clinical Setting Using Dynamic Susceptibility Contrast Enhanced MRI with Automated Localized Arterial Input Function Selection Versus Manual Global Arterial Input Function Selection

Adam M. Winchell^1,2, Ulrike Lobel¹, Jan Sedlacik¹, Ralf Loeffler¹, Zoltan Patay¹, Michael Hamm³, Claudia Hillenbrand¹

¹Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; ²Biomedical Engineering, University of Memphis, Memphis, TN, USA; ³Siemens Medical Solutions, USA

Perfusion weighted imaging has increasingly been used to assess brain perfusion in various clinical settings such as cerebral ischemia, arteriovenous malformations or for characterization of brain tumors. In contrast to manual and global arterial input function (AIF) selection, automated evaluation of dynamic susceptibility contrast-enhanced data using a local AIF minimizes deconvolution errors due to the effects of delay and dispersion of the contrast agent bolus. Furthermore, inter-rater variability selecting the AIF is eliminated. Aim of our study was to compare the reliability of CBF values detected by the different techniques exemplarily in a pediatric patient with diffuse brain stem glioma.

                  2276.     Characterization of Angiogenic Subtypes of Oligodendroglioma by MR-Perfusion Imaging

Gurpreet Singh  Kapoor¹, Timothy Gocke¹, Sanjeev Chawla², Ali Nabavizadeh², Robert G. Whitmore¹, Harish Poptani², Joanna Lopinto¹, Justin Plaum¹, Eileen Maloney-Wilensky¹, Elias R. Mehlem², Donald M. O'Rourke¹

¹Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA; ²Radiology, University of Pennsylvania, Philadelphia, PA, USA

We utilized MR perfusion-weighted imaging to correlate rCBV with the angiogenic markers and EGFR gene amplification in 39 patients with cytogentically distinct oligodendroglial neoplasms. In grade II 1p19q LOH (Group 1) tumors, rCBV values were higher than 1p19q intact (Group 2) tumors. All high-grade tumors, including EGFR-amplified subtype (15%), showed higher rCBV than low-grade tumor. The mRNA levels of VEGF, CD31 and CD105 were higher in Group 1 than Group 2, independently of the EGFR-amplified subtype. Collectively, our data demonstrate that advancements in MR imaging may facilitate molecular subtyping and define distinct angiogenic profiles in cytogenetic subsets of oligodendroglial tumors.

                  2277.     Local Arterial Input Fucntions in DCE-MRI

Jacob U. Fluckiger¹, Matthias C. Schabel¹, Edward VR DiBella¹

¹University of Utah, Salt Lake City, UT, USA

We have developed blind deconvolution algorithms for estimating the AIF directly from DCE-MRI tissue curves. The input functions estimated from tissue curves are delayed and dispersed as compared to those measured directly from the vasculature. Other papers have shown that the AIF changes spatially in the brain, and that locally measured AIFs may provide better parameter estimates. This work attempts to track changes in locally estimated AIF in other regions of the body to support the hypothesis that CA delivery to diseased tissues is more dispersed than that measured in the arteries.

                  2278.     To Assume or Not to Assume Blood T₁ for AIF Measurement in DCE-MRI?

Caleb Roberts¹, David L. Buckley¹, Geoff J. Parker¹

¹Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, The University of Manchester, Manchester, Greater Manchester, UK

In DCE-MRI studies, an important step in calculating contrast agent concentration is the measurement of T₁ in both the tumor tissue and blood AIF. Errors such as blood inflow and B₁ inhomogeneity may suggest that use of an assumed T₁ is more reliable and would reduce these errors. We test the validity of this approach in a typical 3-D DCE-MRI study employing a multiple flip angle T₁ estimate and find that to maximize volume coverage for AIF measurement and to minimize errors in K^trans, v_e and v_p a T₁ measurement must be used in favor of an assumed value.

                  2279.     Automated Principal Component Analysis (PCA) Filtering for Denoising DCE-MRI Data

Balvay Daniel¹, Nadjia Kachenoura², Isabelle Thomassin¹, Rokhaya Thiam¹, Laure Fournier^1,3, Yves Rozenholc⁴, Charles André Cuenod^1,3

¹LRI EA 4062, Université Paris Descartes, Paris, France; ²UMR_S 678, Université Pierre et Marie Curie, Paris, France; ³Service de Radiologie, Hôpital Européen Georges Pompidou, Paris, France; ⁴MAP5 - UMR CNRS 8145, Université Paris Descartes, Paris, France

Dynamic Contrast Enhanced MRI is impaired, for small or heterogeneous lesion, by low signal to noise ratio (SNR), providing poor drawing of region of interest, of noisy microcirculatory parametric maps. To improve SNR without limiting the spatial or the time resolution by low pass filter, a Principal Component Analysis time filtering (PCA-TF) was performed. The number of PCA-TF factors was automatically identified by using the Fraction of Residual Information. The tests on DCE-MRI series showed an obvious denoising efficiency of the adapted PCA-TF with a minimal loss of information.

                  2280.     Simulation Studies of Impulse Response Functions for DCEMRI: Comparing a New Mathematical Model with a Single Exponential Decay Function in the Two-Compartment Model.

Xiaobing Fan¹, Gregory S. Karczmar¹

¹Radiology, The University of Chicago, Chicago, IL, USA

Ideally one would like to study contrast media uptake and washout from the tumor itself, without systematic errors or bias caused by the use of inappropriate physiologic models and incorrect arterial input function in dynamic contrast enhanced MRI (DCEMRI). The impulse response function (IRF) in the conventional two-compartment model assumes a single decaying exponential that may not valid for tumor. Therefore, we employed a new IRF with bi-exponential decay; this may have greater potential as a diagnostic method for cancer using DCEMRI. The proposed IRF is tested with both simulations as well as data from a rodent cancer model.

                  2281.     Can Contrast Extravasation Be Separated from Intravascular Recirculation in DSC MRI of the Brain?

Yi-Ying Wu¹, Ho-Ling Liu^2,3

¹Institute of Medical Physics and Imaging Science, Chang Gung University, Kwei-Shan , Tao-Yuan, Taiwan; ²Institute of Medical Physics and Imaging Science, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; ³MRI Center, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan

In the DSC MRI of brain tumors, previous investigations found elevated tracer concentration during the recirculation phases and interpreted as the degree of vascular tortuosity or contrast extravasations in the tumors. In principle, the contrast leakage can appear as additive or subtractive effects to the intravascular recirculation. This study proposed a model to separate the intravascular and the extravasation components during the recirculation phase. The results showed difficulties to extract vessel permeability information from DSC time curves, when there are co-exist intravascular components. Although the contrast leakage during the first-pass was observed in our simulation, its sensitivity requires further studies.

                  2282.     Analysis of Vascular Function by DCE-MRI in a Human Endothelial Cell Derived Angiogenesis Model in Mice

Claudia Weidensteiner¹, Wilfried Reichardt¹, Holger Weber², Dominik Paul¹, Oliver Siedentopf², Christoph Schaechtele², Dominik von Elverfeldt¹

¹Dept. of Diagnostic Radiology, Medical Physics, University Hospital Freiburg, Freiburg, Germany; ²ProQinase GmbH, Freiburg, Germany

Vascular function was studied with dynamic contrast enhanced MRI (DCE-MRI) in a new angiogenesis model in vivo. Human endothelial cells embedded in a Matrigel matrix formed a functional neovasculature after these Matrigel plugs were implanted into mice. DCE-MRI showed that the plugs were perfused which was confirmed by immunohistochemistry. DCE-MRI data were fitted with a two-compartment model. Anti-angiogenic treatment decreased the fitted transfer constants and areas under the enhancement curves as compared to control plugs which indicated a decreased perfusion.

                  2283.     Parameter Fits Using Measured Population AIF Vs. Literature AIF in DCE-MRI of Pancreatic Cancer Xenograft Model

Andrew C.H. Yung¹, Sylvia Ng^1,2, Jennifer Flexman¹, Jenny C.H. Tso¹, Donald Yapp^1,3, Piotr Kozlowski¹

¹University of British Columbia, Vancouver, BC, Canada; ²British Columbia Cancer Research Centre; ³British Columbia Cancer Research Centre, Vancouver, BC, Canada

We show here that perfusion parameter fits are improved when a population-averaged AIF is extracted from the DCE data in the current study, versus an assumed literature AIF (Lyng MRM 1998). DCE-MRI data were acquired in a xenograft mouse model of pancreatic cancer. Pixels were manually selected from the abdominal aorta from the contrast scans of study animals for inclusion into the population-averaged AIF. Chi-square reflects how closely the fits matched the data. In a representative tumour, using the literature AIF versus the measured population-averaged AIF produced higher chi-square in 85% of voxels (median increase in chi square was 38%).

                  2284.     Evaluation of Functional and Structural Characteristics of Tumor Angiogenesis in Lung Cancer Overexpressing Different VEGF Isoform in a Murine Xenograft Model by Using of MR Imaging

Chia-Ming Shih^1,2, Ang Yuan³, Chih-Yuan Chen², Hao-Wei Cheng³, Chien-Yuan Lin², Pan-Chyr Yang³, Jyh- Horng Chen¹, Chen Chang²

¹Department of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; ²Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; ³National Taiwan University Hospital, Taipei, Taiwan

Vascular endothelial growth factor (VEGF) is important for tumor associated angiogenesis. However, the different effects of VEGF isoforms (such as VEGF121, VEGF165 and VEGF189) in functional and structural characteristics of tumor angiogenesis is still unclear. The purpose of this study was to use dynamic contrast enhanced MRI and steady state contrast enhanced MRI to evaluate the in vivo vascular function using vascular transfer constant (Ktrans), and structural characteristics including microvessel density and vessel size of tumor angiogenesis induced by different VEGF isoform in non-small cell lung cancer.

                  2285.     An Improved Reference Tissue Approach for Measuring the Arterial Input Function in DCEMRI; Comparison of Late-Phase Reference Tissue and Plasma Contrast Media Concentrations.

Xiaobing Fan¹, Chad R. Haney¹, Devkumar Mustafi², Marta Zamora¹, Erica J. Markiewicz¹, Gregory S. Karczmar¹

¹Radiology, The University of Chicago, Chicago, IL, USA; ²Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA

Accurate measurement of the arterial input function (AIF) is critical for quantitative evaluation of DCEMRI data. The reference tissue method avoids large errors associated with direct arterial measurements, but assumes that Ktrans and ve for the reference tissue are close to literature values. Here we demonstrate that this problem can be avoided by comparing a reference tissue that has low blood flow to plasma concentrations measured at one minute or greater after injection – when plasma concentration can be measured accurately. These values (Ktrans/ve) are then used to calculate the entire AIF including the first pass of the contrast bolus.

                  2286.     Simultaneous Determination of Blood Flow, Microvascular Permeability and Blood Volume in Lung Cancer Overexpressing Different VEGF Isoforms in a Murine Xenograft Model by Dynamic Contrast Enhancement MR Imaging (DCE-MRI)

Chia-Ming Shih^1,2, Ang Yuan³, Chih-Yuan Chen², Hao-Wei Cheng³, Ta-Wei Chou², Pan-Chyr Yang³, Jyh- Horng Chen¹, Chen Chang²

¹Department of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; ²Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; ³National Taiwan University Hospital, Taipei, Taiwan

Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. However, biologic effects of different VEGF isoforms (such as VEGF121, VEGF165 and VEGF189) on in vivo tumor associated angiogenesis is still not clear. Adiabatic approximation to the tissue homogeneity model (AATH model) is a newly development which can be used to produce simultaneously specific angiogenic parameters, including blood flow (Fp), permeability (PSp) and blood volume (Vb). In the present study, we apply AATH model to assess angiogenesis in lung cancer overexpressing different VEGF isoforms in a murine xenograft model.

                  2287.     Exploring Optically-Derived Uptake Functions in the Context of Dynamic Contrast-Enhanced MRI Arterial Input Function Measurement

Ross A. Little¹, Marietta Scott², Jane Halliday², Geoff J. Parker¹

¹Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK; ²Imaging, Translational Sciences, AstraZeneca, Cheshire, UK

When acquiring arterial input functions (AIFs), high spatiotemporal resolution is required to capture intrinsic variability. This is especially challenging if simultaneous tissue measurements are made. Optical techniques could allow simultaneous measurement at higher temporal resolution of both the AIF and the tissue of interest. A light sensor was constructed to investigate whether an optical tracer could be observed in an experiment which could be adapted to allow simultaneous DCE-MRI measurement. This combined a photoplethysmograph to locate arterial signals and an absolute light signal intensity monitor. Further work is required to quantify measurements in concentration terms and simultaneously acquire DCE-MRI data.

                  2288.     Comparing Single-Shot Look Locker T1 Mapping and Dynamic 3D T1-Weighted Gradient Echo Imaging for Free Breathing Quantitative DCE-MRI in a Rat Liver Tumor Model at 1.5 T

Andreas Steingoetter¹, Jonas Svensson^1,2, Stefanie Remmele³, Rene Botnar^1,4, Markus Schwaiger¹, Ernst Rummeny⁵, Rickmer Braren⁵

¹Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; ²Department of Medical Radiation Physics, Malmoe University Hospital, Lund University Malmoe, Malmoe, Sweden; ³Philips Research Europe-Hamburg, Hamburg, Germany; ⁴Division of Imaging Sciences, King’s College London School of Medicine, London, UK; ⁵Department of Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

Dynamic 3D T1-weighted gradient-echo (3DT1GRE) sequences for DCE-MRI are prone to displacement errors, motion and flow artefacts. This study compares a 2D single-shot Look-Locker T1 mapping (LLRGC) technique with a standard 3DT1GRE for non-triggered, free-breathing DCE-MRI experiments in a rat liver tumor model. For both methods, data of tumor, liver and muscle were dynamically sampled at 6s intervals after bolus-injection of a double-dose of GD-DTPA. Pharmacokinetic modelling was applied and T10, delay time Td, renal clearance rate rc, Ktrans and ve as well as goodness-of-fit were compared. 3DT1GRE underestimated Ktrans and ve for all tissues and showed lower goodness-of-fit values.

                  2289.     Dual-Relaxation, Temporally-Constrained, Dynamic Contrast-Enhanced MRI Using Inversion Recovery TrueFISP

Simon Walker-Samuel¹, Matthew Orton¹, Lauren C. Baker¹, Jessica K. Boult¹, Simon P. Robinson¹

¹Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research, Sutton, Surrey, UK

Dynamic contrast-enhanced MRI data is increasingly acquired using inversion-recovery (IR) TrueFISP imaging sequences due to their speed and high signal-to-noise. However, IR-TrueFISP is also sensitive to changes in T2 induced by paramagnetic contrast agents. In this study, a dual-relaxation, maximum-likelihood approach is proposed and evaluated in orthotopic prostate tumours, that evaluates and quantifies changes in both T1 and T2. This approach simultaneously models all dynamic IR-TrueFISP data acquired with multiple inversion times, which affords temporal constraint to dynamic T1 estimates. Furthermore, it incorporates the Rician noise distribution evident in magnitude MR data, thereby minimising bias within parameter estimates.

                  2290.     Perfusion Changes Following EGFR Targeted Hollow Gold-Nanoshell Mediated Heating of Tumors

Anil Shetty¹, Marites P. Melancon¹, Andrew Elliott¹, Qian Huang¹, Xiaoxia Wen¹, Chun Li¹, John D. Hazle¹, R Jason Stafford¹

¹The University of Texas M.D.Anderson Cancer Center, Houston, TX, USA

The study goal was to investigate effects of EGFR targeted hollow-gold nanoshell(C225-HGNSs) heating, as monitored with MR temperature imaging, on tumor perfusion, as observed by dynamic contrast MRI (DCE-MRI) and Doppler microultrasound(dUS) and evaluate subsequent tumor drug uptake. 24 hours post-injection of C225-HGNSs, mice were irradiated with 808 nm laser at 4W/sq.cm for 3min. Dual MR/optical imaging agent used as surrogate drug, was injected intravenously at 5 min and 24 h post-heating. DCE-MRI and dUS of C225-HGNSs group demonstrated a multifold increase in vascular perfusion compared with the control, and subsequent enhanced delivery of surrogate agent to the tumors.

                  2291.     Interrogation of Fluctuating Tumour Microvasculature Using Combined Carbogen-USPIO (CUSPIO) Imaging

Jake Samuel Burrell¹, John C. Waterton², Anderson Ryan², Simon P. Robinson¹, Simon Walker-Samuel¹

¹The Institute of Cancer Research, London, Sutton, UK; ²AstraZeneca, Cheshire, UK

Combined carbogen-USPIO (CUSPIO) imaging was used to investigate microvascular fluctuations SW1222 and HCT116 colorectal xenografts. CUSPIO exploits the inherent size difference in the mechanism of action of carbogen (95% O₂, 5% CO₂) and USPIO imaging (erythrocytes compared to nano-particles). Small vessels allow favourable entry to the USPIO particles. By producing δR2* maps temporal changes in vascular perfusion can be evaluated. This technique revealed a difference in the vascular stability of the two tumour types which has important implications for drug trials. This result suggests that CUSPIO imaging is a potentially useful method for imaging transient vascular shutdown in vivo.

                  2292.     The Utility of Gd-DTPA Labeled Red Blood Cells as a Contrast Agent for DSC-MRI Studies

S. Nicole Driggins¹, John Gore¹, C. Chad Quarles¹

¹Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA

The goal of this study is to investigate the utility of Gd-DTPA labeled red blood cells (RBCs) as a contrast agent (CA) for Dynamic Susceptibility Contrast (DSC)-MRI studies. Bolus injections of labeled RBCs generated susceptibility-induced changes in DSC-MRI signal time courses, but these time courses were uncharacteristically heterogeneous across normal brain tissue, exhibited prolonged transit times and were smaller in magnitude than those measured using conventional CAs. These features are possibly the result of RBC coagulation and a subject of ongoing investigation. However, in the studies to date, CA labeled RBCs do exhibit potential as a DSC-MRI CA.

                  2293.     Simultaneous Dynamic Contrast-Enhanced MRI of Four Mice with Induced Tumors on a 1.5 T Clinical Scanner

Stefan Fischer¹, Stefan Weber¹, Kerstin Münnemann¹, Florian M. Meise¹, Jürgen Brieger², Wolfgang G. Schreiber¹

¹Section of Medical Physics, Department of Diagnostic and Interverntional Radiology, Mainz University Medical School, Mainz, RLP, Germany; ²Department of Otolaryngology, Mainz University Medical School, Mainz, RLP, Germany

The aim of this project was to evaluate the feasibility of simultaneous imaging of tumor perfusion with multiple small animals on a 1.5 T clinical scanner. A homebuilt 4-channel receive array was used for this experiment. The examined small animals were nude mice bearing induced squamous cell carcinoma. The DCE-MRI delivered analyzable results. This was possible without sacrificing image quality in comparison to single animal imaging with highest possible resolution depending on gradient field strength.

                 2294.     Prostate Volume in Sexually Immature and Mature Dogs as Measured by MRI

Paul J. McCracken¹, Marie Holahan¹, Stephanie Born², Sairam Bellum², Nicholas Gatto³, Donald S. Williams¹

¹Imaging Department, Merck Research Laboratories, West Point, PA, USA; ²Toxicological Sciences, Merck Research Laboratories, West Point, PA, USA; ³Pathology, Merck Research Laboratories, West Point, PA, USA

MRI may contribute to drug development is augmenting traditional histopathology and complementing histopathological evaluations. Prostate volume is of interest for comparison to pathology, therapeutic effects, or adverse effects. We evaluated MRI as a non-invasive marker of prostate volume in sexually immature dogs and sexually mature dogs, as well as prostate volume change over 4 weeks. There was a significant amount of age-related prostate volume change in 4 weeks. The comparison to ex-vivo absolute prostate weights at necropsy shows a high correlation (R2=0.916). This demonstrates that Magnetic Resonance Imaging may be used to accurately monitor prostate volume, and therefore weight.

                  2295.     Assessing Thermal Damage Using Dynamic Contrast Enhanced MRI

Steffen Lund Hokland^1,2, Thomas Nielsen^1,3, Chrit T. W. Moonen⁴, Hans Stødkilde-Jørgensen², Michael R. Horsman¹, Michael Pedersen²

¹Department of Experimental Clincal Oncology, Aarhus University Hospital, Aarhus C, Denmark; ²The MR-Research Centre, University of Aarhus, Aarhus N, Denmark; ³Interdisciplinary Nanoscience Center (iNANO), University of Aarhus, Aarhus, Denmark; ⁴Imagerie Moléculaire et Fontionelle de la Physiologie á la Thérapie, University of Bordeaux, Bordeaux, France

Hyperthermia is a powerful enhancer of radiation in oncology even when the hyperthermia treatment does not affect tumor growth by it self. The aim of the study was to investigate whether DCE-MRI could be employed to assess hyperthermia induced tumor damage. Using our specially constructed small animal MRI-guided Focused Ultrasound system in conjunction with pre and post treatment DCE-MRI, we found that the semi-quantitative and model based parameters inferred from DCE-MRI data consistently identified hyperthermia treated tumors over non-treated, at doses that did not affect tumor growth.

                  2296.     Magnetic Resonance Imaging Demonstrating Reduction of Edema by Anti-Angiogenic Treatment in a Brain Metastasis Mouse Model

Luhua Zhang¹, Jeeva Munasinghe², Juan Juan Yin¹, Alan Koretsky², Kathleen Kelly¹

¹National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; ²National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

Brain metastases are a common occurrence in cancer patients and its associated edema is an important cause of morbidity and mortality. Current treatments are limited with undesirable side effects. We have developed a mouse model of brain metastasis associated edema. T2 scans and DWI show the development of edema, which is confirmed by histology. After treatment with AZD2171, a VEGF receptor antagonist, T2 scans and DWI show a dramatic reduction of edema. Non-invasive imaging of this model has allowed the evaluation of the effectiveness of anti-angiogenic treatment.

                  2297.     RAFF Contrast During Gene Therapy of Rat Brain Tumors: Association with Cell Density in Tissue Undergoing Apoptotic Cell Death

Timo Liimatainen¹, Alejandra Sierra-Lopez², Timothy Hanson³, Dennis J. Sorce¹, Michael Garwood¹, Shalom Michaeli¹, Olli Gröhn²

¹Center for Magnetic Resonance Research, Dept. of Radiology, University of Minnesota, Minneapolis, MN, USA; ²A.I.Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland; ³Department of Biostatistics, University of Minnesota, Minneapolis, MN, USA

We studied an applicability of recently developed method called relaxation along fictitious field (RAFF) for detection of apoptotic cell death in a rat glioma gene therapy model. We demonstrated that using RAFF method the relaxation times can be reliably measured using different orientations of the fictitious field relative to the rotating frame of reference in vivo. The associations between RAFF relaxation time and trace of water diffusion tensor were found to show similar trend as continuous-wave spin-lock experiments. Measurements with RAFF associated with cell density in investigated tumor regions indicating high sensitivity of RAFF for small alterations in cell density.

                  2298.     Mechanisms of Apparent Diffusion Coefficient Change at Early and Late Stages of Apoptosis

Colleen Bailey^1,2, Anoja Giles^1,3, Gregory J. Czarnota^1,3, Greg J. Stanisz^1,2

¹Medical Biophysics, University of Toronto, Toronto, ON, Canada; ²Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; ³Radiation Oncology and Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Acute myeloid leukemia cells were treated with cisplatin to induce apoptosis. Diffusion MRI at a range of b-values yielded apparent diffusion coefficients that were not significantly different from controls at early stages of apoptosis, but were significantly higher at late stages. These changes cannot be fully accounted for by increased extracellular water and volume fractions. A component of the increase may be due to altered cell shape from membrane blebbing.

                  2299.     Molecular Magnetic Resonance Imaging: Implications to the Detection of Apoptosis

Patrick Rapley¹, Katy Lynn Rich², Mary Lynn Tassotto¹

¹Medical Physics, Thunder Bay Regional Health Science Centre, Thunder Bay, Ontario, Canada; ²Physics, Lakehead University, Thunder Bay, Ontario, Canada

This investigation demonstrates the feasibility of imaging the therapeutic response of HL-60 (human leukemia) cells by establishing a quantitative relationship between T2 enhancment and apoptotic extent. Heat shock induced apoptosis was probed by tagging with Annexin-V+SPIO in vitro and subsequent analysis of the transverse relaxation (T2) measured with a multi echo spin echo MRI acquisition. The results determined a linear relationship between spin-spin relaxivity (R2) and the percentage of apoptosis and also an increase in R2 as the concentration of cells increases. Targeting these nanoparticles to a specific biomarker enables the detection different levels of cell death using a clinical MRI.

                  2300.     Dynamic Contrast-Enhanced MR Imaging Detected Early Changes in Vascular Permeability Following Anti-DR5 Antibody Therapy in Breast Tumor Xenografts

Hyunki Kim^1,2, Karri Folks¹, Lingling Guo³, James George³, Yanhui Sun⁴, Kurt Zinn¹

¹Radiology, University of Alabama at Birmingham, Birmingham, AL, USA; ²Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA; ³Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; ⁴Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

We performed sequential DCE-MRI every 24 hours over 3 days, detecting significantly lower Ktrans levels in breast tumors responsive to anti-DR5 antibody, anti-VEGF antibody, and combination therapies. Sequential DCE-MRI may provide a sufficient number of data points to enable non-linear mathematical modeling for vascular permeability changes; the non-linear characteristics could be considered as a time-independent imaging biomarker. Further, the novel technique of localizing the tumor region of interest to a 0.5-mm peripheral region enhances Ktrans quantification accuracy markedly and can be translated to clinical trials immediately. The proposed techniques may be utilized to improve “Personalized Medicine” during breast-tumor preoperative therapy.

                  2301.     Optimization of Bevacizumab Dosing in Brain Tumors Using MRI Measures of Enhancing Tumor Volume and Relative Cerebral Blood Volume

Kimberly R. Pechman^1,2, Shekar N. Kurpad^1,2, Deborah L. Donohoe^2,3, Devyani P. Bedekar^2,3, Kathleen M. Schmainda^2,4

¹Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA; ²Translational Brain Tumor Program , Medical College of Wisconsin, Milwaukee, WI, USA; ³Radiology, Medical College of Wisconsin, Milwaukee, WI, USA; ⁴Radiology and Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA

Promising results have been obtained with the anti-angiogenic agent, bevacizumab, for the treatment of brain tumor patients. Despite these early promising results, the optimal dose and drug combinations have not yet been defined. The purpose of this study was to characterize the bevacizumab dose-response relationship for brain tumors by measuring the contrast-agent enhanced tumor volumes and relative cerebral blood volume (rCBV) using dynamic susceptibility contrast (DSC) imaging. The studies, performed in the U87 brain tumor model, demonstrated that the optimal dose depends on the method of evaluation used and the time post-treatment that the tumor is evaluated.

                  2302.     Changes in Breast Tumor Kps and ADC After Treatment with the VEGFR-TK Inhibitor AG-013736 Correlate with Changes in Tumor Volume

Lisa J. Wilmes¹, Ka-Loh Li, Lisa M. Fleming, Maria G. Pallavicini², Savannah C. Partridge³, Sheye Aliu, Nola M. Hylton

¹University of California San Francisco, San Francisco, CA, USA; ²University of California Merced; ³University of Washington

Dynamic contrast enhanced (DCE) and diffusion weighted magnetic (DW) resonance imaging were utilized to investigate the treatment effects of the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), AG-013736, in cohort of mice bearing human breast tumor xenografts. MRI data acquired after 7 days of treatment showed a large decrease in tumor endothelial transfer constant, Kps and an increase in tumor ADC in treated tumors. In contrast the mean tumor Kps and ADC values in the control group both decreased slightly over time. The changes in Kps and ADC in the treated group were seen in conjunction with tumor growth inhibition. Control tumors continued to grow. Multivariate analysis showed that both the decrease in tumor Kps and the increase in ADC are independently and significantly correlated with change in tumor volume.

                  2303.     Effect of Vascular Targeting on Tumor Vessel Volume and Size Distribution

Thomas Nielsen^1,2, Lise Bentzen¹, Michael Pedersen³, Michael Robert Horsman¹, Leif Østergaard²

¹Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; ²Center of Functionally Integrative Neuroscience, Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark; ³MR Research Center, Aarhus University Hospital, Aarhus, Denmark

The vascular disrupting agent combretastatin A-4 disodium phosphate (CA4DP) acts on dividing endothelial cells. We hypothesize that CA4DP affects tumor vessels of particular sizes. The aim of this study was to evaluate the effect of CA4DP by vessel size imaging in murine C3H mammary carcinomas. Histograms of blood volume and vessel radius showed general decrease in blood volume and reduction of vessels with radii in a certain range in treated animals compared to controls. VSI may on sight be valuable in estimation of tumor angiogenic status and prediction of response to vascular disrupting agents.

                  2304.     Improvement of Colorectal Liver Metastases Detection Sensitivity and Specificity by Hemodynamic Response Imaging Combined with a Machine Learning Approach

Yifat Edrei^1,2, Moti Freiman³, Eitan Gross⁴, Nathalie Corchia¹, Leo Joskowicz³, Rinat Abramovitch^1,2

¹The Goldyne Savad Inst. for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel; ²MRI/MRS lab HBRC, Hadassah Hebrew University Medical Center, Jerusalem, Israel; ³School of Engineering and Computer Science, The Hebrew University, Jerusalem, Israel; ⁴Pediatric Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel

Colorectal liver metastases (CRLM) are a major cause of death of colorectal-arcinoma patients. Recently, we demonstrated the feasibility of Hemodynamic Response Imaging (HRI), an fMRI method combined with hypercapnia and hyperoxia, for monitoring liver perfusion. In CRLM animal model, we compared the HRI sensitivity to the standard DCE-MRI perfusion-imaging. Furthermore, we developed software, based on a machine-learning approach, for the interactive classification of suspected-CRLM. We concluded that HRI has a higher sensitivity to subtle changes in liver blood-flow induced by CRLM than DCE-MRI, and that the machine-learning approach can provide a useful assistance to early and accurate detection of CRLM.

                  2305.     Fiducial Markers for Correlation of Whole-Specimen Histopathology with MR Imaging at 7T

Deirdre Maria McGrath¹, Roxana M. Vlad², Warren D. Foltz¹, Kristy K. Brock^1,3

¹Radiation Medicine Program, Princess Margaret Hospital, University Health Network,, Toronto, Ontario, Canada; ²Radiation Medicine Program, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; ³Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

Histology provides the “gold standard” for tumor delineation and the assessment of tumor response to cancer treatment. There is a growing role for multi-modality image registration with histology in radiotherapy in order to estimate the anatomical changes during and following radiotherapy. However, fixation and pathology techniques change tissue properties non-uniformly and the margins of the tissue sections are often distorted and sometimes disrupted. Furthermore, differences in sectioning angle and thickness increase the difficulty of correlating cross-sectional imaging and pathological findings. We present preliminary results of testing two injectable fiducial markers for whole-specimen histopatholoy correlation with high-field (7T) MR imaging.

                  2306.     Pattern of Mobile Lipid Accumulation in HeLa Cells During Paclitaxel-Induced Cell Death Using Diffusion-Weighted Spectroscopy.

Dominik Zietkowski¹, Thomas R. Eykyn¹, Geoffrey S. Payne¹, Nandita M. deSouza¹

¹Cancer Research UK Clinical Magnetic Resonance Research Group, The Institute of Cancer Research, Sutton, Surrey, UK

Understanding the pattern of observed changes of mobile lipid resonances would help establish them as a biomarker of drug response. In this study, changes in mobile lipid resonances and their saturation following exposure of HeLa cells to the anti-mitotic drug paclitaxel were investigated using diffusion-weighted (DW) HR-MAS spectroscopy. It was observed that paclitaxel-induced apoptosis is associated with an increase of mobile lipid resonances (including unsaturated lipids) at 24h and a corresponding increase in lipid droplet formation. The pattern of changes in unsaturated lipids observed by 1H NMR may serve as a non-invasive time-course biomarker of apoptotic cell death.

                  2307.     VEGF Overexpression in MCF-7 Breast Cancer Cells Increases Invasion and Lactate Production

Tariq Shah¹, Flonne wildes¹, Venu Raman¹, Zaver M. Bhujwalla¹

¹JHU ICMIC Program, Rusell H. Morgan Department of Radiogy and Radiological Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

The overexpression of VEGF has been associated with tumor progression and poor prognosis in several cancers including breast cancer. VEGF mediates increased microvascular permeability, endothelial cell proliferation, invasion, migration, and survival. In this study we have investigated the invasive properties and metabolism of VEGF165 overexpressing MCF-7 cells using an MR compatible cell perfusion-invasion assay, the Metabolic Boyden Chamber. We observed significant degradation of matrigel by VEGF MCF-7 cells while empty vector (EV) MCF-7 and wild type MCF-7 cells showed negligible degradation. A significant increased lactate levels in VEGF MCF-7 compared to control MCF-7 cells was also observed. The increased lactate production of VEGF MCF-7 cells is consistent with its increased malignancy as increased glycolysis and acidic extracellular pH are associated with a more malignant phenotype. Our data support the possibility that in addition to its known paracrine effects, VEGF can increase invasion and alter metabolism of cancer cells through autocrine signaling, providing additional reasons for targeting this cytokine.

                  2308.     Hyperammonia and Hypoxia Induce Relevant Changes in Lipid Signals in ¹H NMR Spectra from Human Cancer Cells

Sveva Grande¹, Anna Maria Luciani¹, Alessandra Palma¹, Antonella Rosi¹, Orazio Sapora², Vincenza Viti¹, Laura Guidoni¹

¹Dipartimento di Tecnologie e Salute and INFN, Gruppo Collegato Sanità, Istituto Superiore di Sanità, Roma, Italy, Italy; ²Dipartimento di Ambiente e connessa Prevenzione Primaria, Istituto Superiore di Sanità, Roma, Italy, Italy

Tumour tissues are often characterized by intense signals from fatty acids that have been widely studied to provide possible markers of tumour metabolism. We studied the effects of hyperammonia and hypoxia conditions in tumour cells, in order to provide more insight on these lipid metabolites and possible changes in their synthesis. Both hyperammonia and hypoxia induce significant increases in neutral lipid signals. Present data show that 1H NMR can be used to detect accumulation of neutral lipids due to conditions that are frequently encountered in tumour tissues pointing to a possible use as detectors of cell response to modified environment.

                  2309.     Mitochondrial Dysfunction Induces Mobile Lipids and Lipid Droplet Formation: Role of Lipid and Glucose  Metabolism Monitored by 1H and 13C-Edited 1H MRS in Intact HuT 78 Lymphoblastoid Cells

Egidio Iorio¹, Claudia Testa², Francesco De Luca³, Cinzia Casieri⁴, Emanuela Lococo⁵, Roberto Carnevale⁵, Annarita Stringaro⁶, Maria Condello⁶, Giuseppe Arancia⁶, Luisa Lenti⁵, Luisa Lenti⁵, Roberto Strom⁷, Franca Podo¹

¹Cell Biology and Neurosciences, Istituto Superiore di Sanità, Roma, Italy; ²University of Bologna, Italy; ³Physics, University  La Sapienza, Roma, Italy; ⁴University of L'Aquila, L'Aquila, Italy; ⁵Experimental Medicine and Pathology, University  La Sapienza, Roma, Italy; ⁶Technology and Health, Istituto Superiore di Sanità, Rome, Italy; ⁷Cellular Biotechnologies and Haematology, University of La Sapienza, Rome, Italy

Several studies have reported the detection of mobile lipids (ML) signal in 1H MR spectra of intact cells under different physio-patological conditions. In this study we used a complex III inhibitor of mitochondrial electron transport antimycin A (AMC-A) in order to investigate the biochemical nature of ML formation and to monitor alterations of 13C label fluxes from [1-13C]-glucose in intact HuT 78 cells. We observed after 24h AMC-A treatment an over 10-fold increase in the ML signals and an incorporation of 13C label into ML signals. These results may open new perspectives to the development of non-invasive methods for in vivo monitoring the effects of mitochondrial impairment in a number of human diseases.

                  2310.     Tumor Microenvironmental Alterations of Lipid Metabolism Detected by Comparing Cancer Cells with Tumors

Noriko Mori¹, Kristine Glunde¹, Tomoyo Takagi¹, Lin Xiong¹, Flonne Wides¹, Zaver Bhujwalla¹

¹JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Both tumor cells in culture and solid tumor models are essential tools to study cancer biology. Lipids can function as energy storage molecules, structural components of cell membranes and signaling molecules. To understand the differences in lipid components between tumor cells in culture and solid tumors, we compared 1H MRS of lipid-soluble cell or tumor extracts derived from prostate and breast cancer cell lines. Significant differences in fatty acid:cholesterol ratio, the degree of fatty acid unsaturation and phosphatidylcholine:phosphatidylethanolamine ratio, between cells in culture and in tumors, demonstrate the importance of the tumor microenvironment in lipid components.

                  2311.     Imaging the Tumor Macroenvironment: The Effect of Cachectic Tumors on Normal Tissues

Marie-France Penet¹, Samata Kakkad¹, Paul Winnard¹, Dmitri Artemov¹, Zaver M. Bhujwalla¹

¹Department of Radiology and Radiological Science, JHU ICMIC Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

One of the most under explored and yet devastating consequences of cancer is cachexia, a condition in which the body is consumed by deranged carbohydrate, lipid, and protein metabolism. The ability to understand the interaction between the tumor and normal tissues and noninvasively image the sequence of development of this condition would be invaluable in identifying critical stages when the condition becomes life-threatening. Here we have identified imaging indices in preclinical studies that can, in the future, be translated to detect the development of the cachexia cascade in patients.

                  2312.     Genomic Expression and Biochemical Characterization of Enzymes Contributing to the Phosphocholine MRS Signal in Ovary Cancer

Egidio Iorio¹, Alessandro Ricci¹, Maria Elena Pisanu¹, Luisa Paris¹, Massimo Di Vito¹, Paola Alberti², Delia Mezzanzanica², Giancarlo Castellano², Marina Bagnoli², Loris de Cecco², Kristine Glunde³, Zaver Bhujwalla³, Silvana Canevari², Franca Podo¹

¹Istituto Superiore di Sanità, Roma, Italy; ²Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; ³Johns Hopkins University School of Medicine, Baltimore, MD, USA

Elucidation of the mechanisms responsible for the aberrant phosphatidylcholine (PC) metabolism in ephitelial ovarian cancer (EOC) cells may allow identification of novel biomarkers of tumor progression and design of new targeted therapies. In this study we investigated activities and genomic expression of enzymes responsible for PCho accumulation in EOC cells compared with non tumoral immortalized cell variants. The results showed that major contributions to PCho accumulation in EOC cells likely derive from upregulation of choká (about 10x), increase in overall chok activity (about 20x), as well in a up to 17-fold activation of PC-specific phospholipase C.

                  2313.     MRS Observed Effects of Phorbol Myristate Acetate on Lipid Metabolism in DU145 Prostate Tumor Cells

Melissa Suzanne Love¹, Daniel-Joseph Leung¹, Theresa Meganne Mawn¹, Edward James Delikatny¹

¹Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

Phorbol myristate acetate (PMA) is a known activator of PKC and mimetic analogue of diacylglycerol, the cleavage product of PLC. We have investigated the effect of PKC activation by PMA on lipid metabolism in DU145 prostate tumor cells. Perfused DU145 cells were treated with PMA and analyzed with 31P MRS to measure levels of PC. Cultured DU145 cells were also treated with PMA and the phospholipase C inhibitor D609, and extracts were measured by high-resolution 1H MRS to examine levels of choline, PC, and GPC. The data shows that PMA affects lipid metabolism and has antiproliferative effects on DU145 cells.

                  2314.     Identification of Lipids in Tissue Extracts of Astrocytic Brain Tumors

Frauke Nehen¹, Wieland Willker¹, Rudolf Fahlbusch², Dieter Leibfritz¹

¹Institute of Organic Chemistry, University of Bremen, Bremen, Germany; ²International Neuroscience Institute Hannover, Hannover, Germany

Lipophilic tissue extracts of astrocytic brain tumors were analyzed by ¹H-NMR spectroscopy. Tumor core and tumor margin differ at least by one so far unknown metabolite. It contains an olefinic subunit with one quarternary carbon identified by various 2D-NMR methods. Separation of the lipophilic extract revealed that the unknown compound belongs to the neutral lipids and appears preferentially within the triglyceride fraction.

                  2315.     1H MRS Reveals Altered Lactate Levels in Cancer Cells Subjected to MEK1/2 Signalling Inhibition

Maria Falck Miniotis¹, Paul Workman², Martin O. Leach¹, Mounia Beloueche-Babari¹

¹Cancer Research UK Clinical Magnetic Resonance Research Group, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, Surrey, UK; ²Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, Surrey, UK

RAS-B-RAF-MEK-ERK signalling is often deregulated in cancer and represents a significant target for mechanism-based drugs. Our aim was to investigate whether inhibition of this signalling pathway in human cancer cells could lead to magnetic resonance spectroscopy detectable changes in glycolysis that may serve as biomarkers of target suppression. Our findings demonstrate that MEK1/2 signalling inhibition with CI-1040 or PD325901 leads to decreased intracellular lactate levels in human melanoma, colorectal and breast carcinoma cell lines. These results suggest lactate as a potential non-invasive MRS biomarker of response to MEK1/2 targeted therapeutics in human cancer cells.

                  2316.     Cyclooxygenase-2 Silencing of MDA-MB-231 Breast Cancer Cells Reduces Invasion and Alters Metabolism

Tariq Shah¹, Ioannis Stasinopoulos¹, Flonne Wildes¹, Zaver M. Bhujwalla¹

¹JHU ICMIC Program, Rusell H. Morgan Department of Radiogy and Radiological Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

To evaluate the role of cyclooxygenase-2 (COX-2) in human breast cancer cell proliferation and invasion we silenced COX-2 expression in the highly invasive MDA-MB-231 human breast cancer cells. Dynamic tracking of invasion and metabolism was performed with a magnetic resonance (MR) compatible cell perfusion assay under controlled pH, temperature, and oxygenation, over the course of 48 h. COX-2-silenced cells exhibited significantly reduced invasion relative to control cells expressing COX-2. COX-2 downregulation resulted in a significant reduction in choline kinase activity together with reduced total choline, phosphocholine and lactate levels consistent with the less malignant phenotype. Reduced expression of genes involved in invasion such as VEGF-A, MMP-2, and uPAR2 was observed in COX-2-silenced cells. Thus, silencing of COX-2 in MDA-MB-231 breast cancer cells resulted in reduced invasiveness as well as the acquisition of distinctive metabolism characteristics. These results suggest that COX-2 inhibition can effectively reduce tumor invasion and metastasis by poorly differentiated breast cancer cells.

                  2317.     Cellular Glutathione Detected by ¹H NMR Can Give Information on Radio-Sensitivity in Tumour Cells in Vitro

Alessandra Palma¹, Claudio Giovannini², Sveva Grande¹, Laura Guidoni¹, Anna Maria Luciani¹, Antonella Rosi¹, Orazio Sapora³, Vincenza Viti¹

¹Dipartimento di Tecnologie e Salute and INFN, Gruppo Collegato Sanità, Istituto Superiore di Sanità, Roma, Italy, Italy; ²Centro per la Qualità degli Alimenti e per i rischi Alimentari, Istituto Superiore di Sanità, Roma, Italy, Italy; ³Dipartimento di Ambiente e connessa Prevenzione Primaria, Istituto Superiore di Sanità, Roma, Italy, Italy

In previous studies we associated the glutathione (GSH) level -1H NMR detected- to radiation resistance. We then investigated whether i) such correlation holds also in tumour cells from human glioma in cell lines with different sensitivity to irradiation, and ii) a different role can be envisaged for GSH in cells from different tumours. Two adenocarcinoma-derived cell lines were therefore compared to two glioma-derived cell lines. These cell lines showed different radioresistance, consistent with the initial levels of GSH. Radiation resistant cells were then irradiated after Buthionine sulfoximine treatment to decrease the concentration of GSH in cells, preventing its radioprotective effects.

                  2318.     The Nucleotide Sugar UDP-GlcNAc, a Major Glycosylation Precursor, Can Be Observed in Intact Tumour Cells by ¹H NMR in the Low Field Spectral Region

Antonella Rosi¹, Alessandra Palma¹, Sveva Grande¹, Laura Guidoni¹, Anna Maria Luciani¹, Vincenza Viti¹

¹Dipartimento di Tecnologie e Salute and INFN, Gruppo Collegato Sanità, Istituto Superiore di Sanità, Roma, Italy, Italy

Some aspects of sugar metabolism are involved in tumour progression. The dynamic changes in glycosylation levels in response to extracellular stimuli suggest a key role of signal transduction pathways. Nucleotide sugars have elicited much attention, being donor substrates for glycosylation of proteins and lipids.1H NMR was used to observe sugar-related metabolites in cells, in the low region of the spectrum. We observed major hexosamine precursors in two tumour cell lines. Modulation of signal intensities by NH4Cl treatment allowed to assign two nucleotide sugar signals, thus providing a tool for quantitation of these molecules in intact cells and, possibly, in tumour tissues.

                  2319.     Metabolic Characterization of an Imatinib-Resistant Chronic Myelogenous Leukemia Cell Model

Brian James Dewar¹, Kayvan Keshari¹, Rex Errol Jeffries¹, Lee M. Graves², Jeffrey M. Macdonald¹

¹Biomedical Engineering, Univ. of North Carolina, Chapel Hill, NC, USA; ²Pharmacology, Univ. of North Carolina, Chapel Hill, NC, USA

Drug resistance to Imatinib often develops in CML. Here we characterized metabolic differences using NMR, comparing an Imatinib-resistant cell model, MyLR, to a Imatinib-sensitive parental cell line, MyL. Here we describe the first such example of elevated phosphocreatine levels in drug -resistant leukemia cell using conventional MRS metabolomics and NMR compatible bioreactor.

                  2320.     Effect of Androgens on Intracellular Polyamine Levels in Androgen-Dependent and Androgen-Independent Prostate Cancer Cell Lines

Nicholas G. Spencer¹, Eszter Nagy², Nandita M. DeSouza¹, Geoffrey S. Payne¹

¹CRUK Clinical Magnetic Resonance Research Group, Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, UK; ²Human Biomonitoring and Carcinogen Activation, Institute of Cancer Research and the Royal Marsden Hospital, Sutton, Surrey, UK

With the long-term aim to evaluate polyamines as magnetic resonance (MR) markers of androgen-sensitivity in prostate cancer, this study compares polyamine levels in androgen-dependent and androgen-independent cell lines in response to androgen deprivation. An androgen-responsive cell line, 22RV1, showed lower polyamine levels compared to androgen-independent PC-3 cells and, in androgen deprived medium, there was a decrease in polyamines for 22RV1 but not in PC-3 cells. This was confirmed with high performance liquid chromatography and demonstrates the potential of MR in the analysis of polyamine metabolism in-vitro models of prostate cancer.

                  2321.     Tissue Metabolic Concentrations Investigated with Respect to Prognosis for Breast Cancer Patients

Beathe Sitter¹, Tone Frost Bathen¹, Hans Fjøsne², Jostein Halgunset³, Steinar Lundgren^1,4, Ingrid Susann Gribbestad¹

¹ISB, NTNU, Trondheim, Norway; ²Dept. of Surgery, Trondheim University Hospital, Trondheim, Norway; ³LBK, NTNU, Trondheim, Norway; ⁴Dept. of Oncology, Trondheim University Hospital, Trondheim, Norway

In the search for improved treatment and care for breast cancer patients, understanding breast cancer biology is important. For molecular mechanisms studied in vitro to be translated to clinical use, metabolic information should relate to clinically relevant parameters. Breast cancer tissue metabolic concentrations have been quantified and directly correlated to prognostic factors and patient outcome. Biopsies from diseased patients have higher concentrations of choline than samples from patients with good and poor prognosis. Trend towards significance were found for lower GPC in the good prognosis group and higher PC in diseased group compared to poor prognosis group. Significant differences between groups of samples were also found for ratios of GPC/Gly and PC/GPC.

                  2322.     Investigation of Features Related to Androgen Dependency in Prostate Cells Using 1H HRMAS MRS and Principal Component Analysis

Robert Leslie Davidson¹, Nick Spencer¹, Simon J. Doran¹, Nandita M. deSouza¹, Geoffrey S. Payne¹

¹Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK

Principal Components Analysis applied to 1H HRMAS MRS of normal and cancerous prostate cell lines grown with and without androgens to study the metabolic features characteristic of androgen independence. Preliminary studies show a large number of peaks that can discriminate between healthy and cancerous cell lines (P-Cho, Ala and Lac elevated in cancer, Cr and polyamines elevated in healthy cells), and also that creatine is less abundant in androgen insensitive cancer cell lines when grown in the absence of androgen.

                  2323.     Choline Metabolic Composition Correlates to Basal-Like and Luminal a Genetic Subtypes in Orthotopic Breast Cancer Xenografts

Siver Andreas Moestue¹, Else Marie Huuse², Olav Engebråten³, Beathe Sitter², Gunhild Mari Mælandsmo³, Tone Frost Bathen², Ingrid Susann Gribbestad²

¹Institute of Circulation and Medical Imaging, Norwegian University of Science and Technology , Trondheim, Norway; ²Institute of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; ³Department of Tumor Biology, Institute for Cancer Research, Oslo, Norway

Molecular sub-classification of breast cancer based on gene expression analysis represent clinically distinct patient groups. Two new murine breast cancer xenograft model systems, reflecting the basal-like (poor prognosis) and luminal A (better prognosis) subgroups, have recently been established. A significant difference in choline metabolism between the xenograft models was measured using HR-MAS with ERETIC quantification. The choline metabolite pattern shifted towards higher glycerophosphocholine concentration and lower phosphocholine concentration in the fastest growing basal-like xenograft model. The data from our study suggest that a high GPC/PC ratio is associated with fast-growing, aggressive tumors. This may reflect intrinsic differences between the molecular subgroups or differences in tumor microenvironment. Further studies of these xenograft models are warranted in order to explore the prognostic value of the choline metabolic composition in different molecular subgroups of breast cancer.

                  2324.     Metabolomic Analysis of Tissue-Serum Pairs for Human Lung Cancer

Kate W. Jordan¹, Christen B. Adkins¹, Li Su², Eugene J. Mark¹, David C. Christiani^2,3, Leo L. Cheng^1,4

¹Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA; ²Environmental Health, Harvard School of Public Health, Boston, MA; ³Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA; ⁴Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA

With the urgent clinical need for early diagnosis of lung cancer, this project aims to develop a blood serum-based metabolomic screening test that may provide biochemical information indicating the risk of lung cancer and direct patients to further radiological tests for disease detection at clinically asymptomatic stages. Human SCC and adenocarcinoma tissue and serum paired samples from 14 patients, and seven serum samples from healthy controls, were analyzed by high-resolution magic angle spinning MRS. The spectra of tissue and sera showed differentiating capabilities between two cancer types and healthy controls, indicating the potential to assess risk of lung cancer.

                  2325.     Magnetic Resonance Imaging and Ultrasonography of Chicken Egg Tumor Model

Jaak Nairismägi¹, Ott Rovgeiša¹, Taavi Päll¹, Johanna Närväinen², Priit Kogerman¹

¹Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia, Estonia; ²A.I.Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland

Egg models are common in experimental science as they are considered as non-animal experiments. However, imaging methods of eggs are technically complicated because of the egg shell and demanding embryo fixation options. Here we implanted mice melanoma (B16F0) tumor cells to the chorioallantoic membrane of 30 chicken eggs and imaged the tumors before hesting by using ultrasonography, magnetic resonance imaging (MRI) and optical imaging methods. Ultrasonography and optical imaging gave information mainly on the size of tumor, but MRI can show also structural changes inside the tumor. In conclusion, we suggest this very cost-effective model for oncobiological applications.

                  2326.     In Vivo Visualization of Mouse Sciatic Nerves Involved with a Pancreatic Cancer Cells Using Manganese Enhanced MR Imaging Technique.

Hiroaki Mieno^1,2, Masayuki Yamaguchi³, Shuichi Mitsunaga^1,4, Akira Imoto¹, Tarou Ikumoto^1,2, Akira Hirayama^3,5, Akira Nabetani⁵, Atsushi Nozaki⁵, Taira Kinoshita², Hirohumi Fujii³, Atsushi Ochiai¹

¹Pathology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; ²Upper Abdominal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; ³Functional Imaging Division, National Cancer Center Hospital East; ⁴Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East; ⁵GE Yokogawa Medical Systems,Ltd., Tokyo, Japan

A novel application of manganese-enhanced MR imaging (MEMRI) has been explored to visualize mouse sciatic nerves under normal conditions and some pathological conditions, including a human pancreatic cancer xenograft invading the sciatic nerve. Sciatic nerves not involved with the tumor showed high signal intensity on MEMRI 1 day after intraspinal administration of MnCl2, where as tumor tissue retained relatively low signal intensity, allowing better discrimination between the tumor and residual nerve on MRI. MEMRI is, therefore, helpful to depict the tumor invasion front in experimental nerve invasion model of human pancreatic cancer.

                  2327.     Diffusion MRI of Choroid Melanoma Tumor in Mouse Eye

Peng Sun¹, Huiying Zhang², Qing Wang³, Gregory M. Lanza², Sheng-Kwei Song¹, Samuel A. Wickline², Junjie Chen⁴

¹Radiology, Washington University in St. Louis, Saint Louis, MO, USA; ²Internal Medicine, Washington University in St. Louis, Saint Louis, MO, USA; ³Mechanical, Aerospace and Structural Engineering, Washington University in St. Louis, Saint Louis, MO, USA; ⁴Internal Medicine , Washington University in St. Louis, Saint Louis, MO, USA

Choroidal melanoma is the most common intraocular malignancy. The objective of the present study is to quantify apparent diffusion coefficient (ADC) of choroidal melanoma for tumor identification in mice. Mice underwent intraocular inoculation of 50¡Á10³ B16F10 melanoma cells were imaged at 11.74T. Three-direction diffusion weighted images were acquired to derive the ADC map. Tumor mass could be clearly indentified on the ADC map due to the higher ADC of melanoma tumor (0.65¡Á10^-3 mm²/s) than that of the retina (0.36¡Á10^-3 mm²/s). The results suggested diffusion weighted MRI could detect choroidal melanoma in vivo.

                  2328.     BOLD Changes in the Microenvironment Are an Early Marker of Micrometastatic Breast Cancer in the Rat Brain.

Matthew D. Budde¹, E Kay Jordan¹, Melissa Smith¹, Eric M. Gold¹, Joseph A. Frank¹

¹Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, USA

Blood oxygen level dependant (BOLD) MRI is related to tumor oxygenation and perfusion. However, it is unknown whether it can be used for early diagnosis in addition to its prognostic potential. The purpose of this study was to determine the sensitivity of BOLD in detecting developing tumors in a rat model of breast cancer metastasis to the brain. BOLD decreases were often evident prior to the detection of metastases on T2-weighted images. Despite the difficulties in specifically attributing BOLD changes to oxygenation or perfusion, BOLD MRI may aid the detection of developing micrometastatic lesions.

                  2329.     BOLD Signal and T₂ Responses in Rat F98 and 9L Gliomas to Hypoxic Hypoxia

Neil Peter Jerome¹, Khan Hekmatyar¹, Risto A. Kauppinen¹

¹Department of Radiology, Dartmouth Medical School, Hanover, NH, USA

Two rat glioma models, F98 and 9L, were used to study effects of hypoxic hypoxia (12% inspired O2) on BOLD signal and parenchymal T2 at 7T. BOLD signal decreased by 5.3±1.7 and 10.9±4.6% in F98 and 9L gliomas, respectively and the respective T2 changes were -1.8±2.8 and -5.0±2.6ms. MR responses to carbogen (O2:CO2, 95:5) were much less reproducible in both gliomas. AMI-227 data indicated larger increase in blood volume of 9L than in F98 during hypoxia. These data indicate that hypoxic exposure may provide an indirect means of evaluating tumour vascular and metabolic adaptivity.

                  2330.     Apparent Diffusion Coefficient Correlates with Necrosis and Inversely with Proliferation: Histopathological Quantification in a Panel of Human Tumour Xenografts

Jane Halliday¹, Jose Ulloa¹, Marietta Scott¹, Graham Bigley², Herve Barjat¹, Neil Gray², John C. Waterton¹, Chris Womack², Carsten Liess¹

¹Imaging, Translational Sciences, AstraZeneca, Macclesfield, Cheshire, UK; ²Cancer Histopathology, AstraZeneca, Macclesfield, Cheshire, UK

The water proton Apparent Diffusion Coefficient (ADC) has been proposed as a biomarker of the non-viable fraction in tumours. Our aim was to evaluate the correlation between ADC and histopathology in a diverse panel of human tumour xenografts commonly used in a preclinical drug efficacy evaluation. There was a significant correlation between ADC and necrosis (N=19, p=0.02) and a significant inverse correlation with proliferation (N=19, p=0.005), but no correlation with oedema.

                  2331.     Detection of Colonic Tumorigenesis In Vivo and Monitoring of Local Colonic Tumor Invasion and Metastasis in Mice Using Magnetic Resonance Imaging

Devkumar Mustafi¹, Urszula Dougherty², Alessandro Fichera², Reba Mustafi², Xiaobing Fan³, Gregory S. Karczmar³, Marta Zamora³, Marc Bissonnette²

¹Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA; ²Medicine, The University of Chicago, Chicago, IL, USA; ³Radiology, The University of Chicago, Chicago, IL, USA

The primary goal of this study was to develop a new, clinically applicable magnetic resonance imaging (MRI) method for detecting early colonic cancer invasion and distant metastasis to liver and lungs. We have developed a novel mouse model of colon cancer metastasis using cecal implants of colon cancer cells. Based on our results with control and tumor-bearing immunotolerant Rag1 mice, we have demonstrated—for the first time—that in vivo anatomical and functional MRI studies, together with in vitro histological studies, offer the potential for detecting and monitoring early colonic cancer invasion and distant metastasis in a murine model.

                  2332.     Chronic Liver Inflammation-Induced Double-Strand DNA Breaks Enhance Hepatocarcinogenesis

Hila Barash¹, Eitan Gross², Natalie Corchia¹, Irit Cohen¹, Daniel Goldenberg¹, Eithan Galun¹, Rinat Abramovitch^1,3

¹Goldyne Savad Institute for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel; ²Pediatric Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel; ³MRI/MRS lab HBRC, Hadassah Hebrew University Medical Center, Jerusalem, Israel

Hepatocellular-carcinoma (HCC) is the third leading cause of cancer mortality and considered to be the outcome of chronic liver inflammation. Surgical-resection is the preferred treatment for HCC; however, survival rates are suboptimal due to tumor recurrence. Our objective was to understand the molecular mechanisms linking liver regeneration under chronic-inflammation to tumorigenesis. Mdr2-knockout mice, had undergone partial-hepatectomy, and experienced enhanced hepatocarcinogenesis. Yet, liver regeneration was severely attenuated. The inflamed livers had elevated levels of double-stranded DNA breaks resulting in hepatocyte apoptosis and cell-cycle arrest. We propose that under the proliferative stress, the genomic-unstable-hepatocytes reenter the cell cycle, causing the enhanced tumorigenesis.

                  2333.     Registration of Complete 3D Histological Tumor Datasets with in Vivo MRI: First Experience

Flora Henning¹, Robert Haase², Sergey Tokalov¹, Thomas Schulze³, Nasreddin Abolmaali¹

¹OncoRay - MI, Dresden, Germany; ²OncoRay - MP, Germany; ³Siemens Health Care Sector, Germany

After in vivo MR imaging of a human tumor (NSCLC, H1299) xenograft model in nude rats a 1.5 T clinical scanner tumors were excised and sliced completely. Staining of histological slices was done with hematoxiline & eosin. Histologic slices were digitized, co-registered and imported into DICOM environment. Fusion of complete 3D datasets of in vivo rat imaging and ex vivo histology was done using the Syngo software. The suggested technique may be applied to any MRI measurement technique; accordingly knowledge may be gathered on the reality of what we see in MRI.

                  2334.     Examining the Source of T₂ Components Fit with NNLS

Pamela R. Jackson¹, Roland G. Henry², Tracy Richmond McKnight²

¹Joint Graduate Group in Bioengineering, University of California, Berkeley and San Francisco, San Francisco, CA, USA; ²Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA

From a previous study, we questioned the reproducibility and source of multiple T2 components measured from cells suspended in agarose. Using NNLS, multiexponential T2s were fit in samples of different agarose concentrations and in packed cell samples washed in different gadolinium concentrations. Based on the variability in the agar samples, we established a signal fraction threshold for T2 components. Two components were fit in packed cell samples. The longer component decreased with increasing Gd concentration suggesting interaction with the extracellular compartment. This study underscores the necessity of determining thresholds of acceptance for components identified with NNLS.

                  2335.     In Vivo T2 Measurements of Glioma Growth in Mouse Brain at 9.4T

Barbara Blasiak^1,2, Boguslaw Tomanek^1,3, Tadeusz Foniok³, Dave Kirk¹, Abedelnasser Abulrob^4,5, Umar Iqbal⁵, Danica Stanimirovic^4,5, Xuequing Lun¹, Peter Forsyth¹, Garnette Sutherland¹

¹Dept of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; ²Polish Academy of Sciences, Institute of Nuclear Physics, Krakow, Malopolska, Poland; ³Institute for Biodiagnostics (West), National Research Council of Canada, Calgary, Alberta, Canada; ⁴Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada; ⁵Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

The correlation between T2 and the intracranial growth of U87MG deltaEGFR cells in nude mice, as a model of human high grade glioma, was investigated. MSME images of the growing tumor were acquired 10 to 13 days after the injection. We observed that the difference in T2 in the early stage of the tumor growth (< 2 mm3) between cancerous and normal tissue was less than 10%. The difference increased to about 20% when the tumor was larger (> 2.5 mm3). The results provide valuable information about MR imaging strategies, including molecular imaging, at the early stage of cancer development.

                  2336.     Short T2* Components in the Normal Murine Mammary Gland and Pre-Invasive Carcinoma May Aid in Detection of Early Breast Cancer.

Sanaz Arkani Jansen¹, Xiaobing Fan, Erica Markiewicz, Gillian Newstead, Gregory Karczmar¹

¹University of Chicago, Chicago, IL, USA

The sensitivity and specificity of dynamic contrast enhanced MRI for ductal carcinoma in situ (DCIS), the earliest stage of breast cancer in which cancer cells are confined to mammary ducts, needs improvement. Relaxometry of DCIS is important for designing improved imaging methods, however is challenging to perform in women. Here, we use a transgenic mouse model of breast cancer to perform relaxometry of murine DCIS, invasive tumors and normal tissue. Interestingly, we find that normal tissue and DCIS exhibit biexponential decay and short T2* components, suggesting that imaging at shorter TE may help to improve clinical imaging of DCIS.

                  2337.     Molecular MR Imaging of Fibrin in Tumors

Ritika Uppal¹, Zdravka Medarova¹, Christian Farrar¹, Guangping Dai¹, Anna Moore¹, Peter Caravan¹

¹Radiology, Massachusetts General Hospital, Charlestown, MA, USA

The composition of tumor stroma strongly resembles the granulation tissue of healing skin wounds. The fact that cross-linked fibrin is widely found in the stroma of tumors presents the possibility of using a fibrin-targeted contrast agent to characterize tumors. We used a fibrin-specific Gd based agent (EP-2104R) and nonspecific GdDTPA to characterize a breast cancer xenograft mouse model. Dynamic contrast enhanced (DCE) imaging of the tumor core was similar with both agents. However, the enhancement of the tumor periphery persisted over 90 min after injection of EP-2104R, whereas GdDTPA enhanced periphery showed rapid signal washout.

                  2338.     The Ex Vivo and in Vivo MR Study of Glioma Targeted Contrast Agents

Barbara Blasiak^1,2, Boguslaw Tomanek^1,3, Tadeusz Foniok³, David Kirk¹, David Rushforth³, Roger MacKenzie⁴, Abedelnasser Abulrob^4,5, Umar Iqbal⁵, Danica Stanimirovic^4,5, Xuqueng Lung¹, Peter Forsyth¹

¹Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; ²Institute of Nuclear Physics, Polish Academy of Sciences, Krakow, malopolskie, Poland; ³Institute of Biodiagnostics(West), National Research Council of Canada, Calgary, Alberta, Canada; ⁴Institute of Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada; ⁵Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

The composition of targeted contrast agents of gliomas was investigated. The c.a. consisting of Fe3O4 and FeCo cores with SiO2 and Au shells were investigated. The relaxation times of agar solutions of the c.a. were measured ex vivo using 9.4T MRI system. To render NPs targeted high grade glioma specific single domain antibodies were conjugated with the NPs. The ex vivo results showed, that the FeCo core are more efficient than Fe3O4 core NPs. The in vivo MRI using mouse glioma model and functionalized NPs showed decrease in T2 over the tumor area, showing the efficacy of the c.a.

                  2339.     Synthesis and Characterization of the Tumor Targeting Contrast Agent [Gd(TTDA)] ^2- Derivative for MRI

Yun-Ming Wang¹, Ying-Hsiu Lin², Chiao-Yun Chen³, Gin-Chung Liu³

¹Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; ²Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan; ³Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Bombesin (BN) is a 14 amino acid peptide that binds to gastrin-releasing peptide receptors (GRPR). GRPR has been found in a variety of cancers. In order to target GRPR, we modified TTDA derivative ligand L1 and then conjugated with BN peptide substrate. The GdL1-BN and EuL1-BN complexes were conformed by MRI and optical imaging. The results sowed that GdL1-BN had ability to target the PC-3 cell line. These results indicate that GdL1-BN is a suitable candidate for a targeted MRI contrast agent in tracing GRPR over-expression.

                  2340.     Synthesis and Characterization CRGD-PEG Iron Oxide Nanoparticles of Noninvasive Imaging for Targeting α _vβ ₃Integrins by MRI

Yun-Ming Wang¹, Jen-Yen Lin¹, Yu-Ting Kao², Gin-Chung Liu²

¹Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; ²Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

The fabrication and characterization of PEG-coated magnetic nanoparticles, SPIO-mPEG-cRGD as nanoprobes for MR imaging to target specific receptors were reported. From the results, we found that the SPIO-mPEG-cRGD had well-dispersed in different pH value solutions, low protein absorption from medium, no hysteresis, high saturation magnetization and low cytotoxicity of different cells. Moreover, SPIO-mPEG-cRGD had ability to target the MCF-7, HT-29, A549, and HT-1080 cells proved by in vitro and in vivo MR imaging studies.

                  2341.     Weighted Combination of Multichannel ¹H-MRS Data: Comparison of SNR- And SVD-Based Methods by Simulated, in Vitro and in Vivo Data

Alexander Gussew¹, Jacob Orme^1,2, Reinhard Rzanny¹, Jürgen R. Reichenbach¹

¹Medical Physics Group, IDIR, University Clinics of Jena, Jena, Thuringia, Germany; ²Brigham Young University, Provo, UT, USA

Using the phased array RF coils in MRS examinations can distinctly improve spectra quality because of their higher signal sensitivity compared to single channel circular polarized coils. However, exact estimation of channel weights is essential for the correct reconstruction of combined data. The accuracy of two different approaches for the weight extraction first based on channel SNR and second on multi channel data Singular Value Decomposition, were quantitatively compared using simulated as well as experimental in vitro and in vivo multi-channel data sets with two different SNR levels.

                  2342.     Implementation of ¹H MRS at 3.0 Tesla for the Analysis of the Biochemistry and Function of the Amygdala in Patients with Borderline Personality Disorder and Healthy Controls

Mareen Hoerst¹, Wolfgang Weber-Fahr¹, Nuran Tunc-Skarka¹, Matthias Ruf¹, Christian Schmahl², Gabriele Ende¹

¹Department of Neuroimaging, Central Institute of Mental Health, Mannheim, Germany; ²Department of Psychosomatic and Psychotherapeutic Medicine, Central Institute of Mental Health, Mannheim, Germany

The core of borderline personality disorder (BPD) is a neuronal dysfunction in a frontolimbic network. The amygdala is a key region of the limbic system and plays an important role in impulsivity, affect regulation and emotional information processing, and thus are related to BPD symptoms. In contrast to other brain regions the amygdala is an extremely difficult region to acquire spectra from. We used ¹H MRS at 3T to determine alterations of the metabolism in a precisely defined voxel within the left amygdala in BPD patients compared to controls. Decreased levels of N-acetylaspartate and total creatine in patients were observed.

                  2343.     Single Voxel Spectroscopy in Different Regions of Human Brain at 7 T

Malgorzata Marjanska¹, Edward J. Auerbach¹, Pierre-Francois Van de Moortele¹, Gregor Adriany¹, Michael Garwood¹

¹Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN, USA

Proton Magnetic Resonance Spectroscopy provides a noninvasive way to investigate in vivo neurochemical abnormalities of many brain disorders. Each observable metabolite can potentially provide unique information about brain biochemistry and be a biomarker for brain disorders which will facilitate diagnosis and treatment. Spectra of exceptional quality have been obtained and quantified previously at 7 T from human occipital lobe. However, for many brain disorders the neurochemical abnormalities are not expected to occur in occipital lobe, but in other brain structures. In this project, we investigate the ability to obtain high quality 7 T spectra from different brain regions.

                  2344.     Cerebral Glutamate Metabolism Via [2-13C] Glucose in Normal Brain

Napapon Sailasuta¹, Kent Harris¹, Osama Abulseoud², Brian Ross¹

¹HMRI, Pasadena, CA, USA; ²Psychiatry, U of Southern California, Los Angeles, CA, USA

The aim of this study was to validate an alternative approach to study cerebral glucose metabolism in normal brain by using 13C magnetic resonance spectroscopy (MRS) using C2 glucose infusion via glutamate C5 resonance.

                  2345.     GABA Detection Via PRESS Constant Echo Time Difference Spectroscopy

Jeff Snyder¹, Richard B. Thompson², Alan H. Wilman^1,2

¹Physics, University of Alberta, Edmonton, Alberta, Canada; ²Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada

The signal of GABA at 3 ppm in proton spectroscopy is hindered by the large overlapping creatine resonance, requiring alternate methods for detection. This work proposes a PRESS constant echo time difference spectroscopy approach to suppress the creatine signal while maintaining GABA. The technique is simple to implement and only requires changes to timing and flip angle parameters in a standard PRESS sequence. This method is illustrated at 4.7 T.

                  2346.     Histidine Transport Dynamics Across the Healthy Human Blood-Brain Barrier Investigated by 1H MRS

Daniel Guo Quae Chong¹, Jean-Marc Nuoffer², Peter Vermathen¹, Johannes Slotboom³, Chris Boesch¹, Roland Kreis¹

¹Department of Clinical Research, University of Bern, Bern, Switzerland; ²Metabolic Unit, Inselspital, Bern, Switzerland; ³Neuroradiology, Inselspital, Bern, Switzerland

Histidine transport across the blood brain barrier (BBB) is investigated using 1H-MRS. Volunteers consume a single high dose of His causing blood His levels to peak at 30 times normal in 1-3 hours. Brain His levels peak ~4 hours after blood His. Blood His shows individual absorption and disposal rates for different subjects, while brain His suggest saturation of His influx across the BBB. Blood His and brain His appear to be linked in each subject. Evaluation of the time series of spectra was performed by simultaneous fitting with prior knowledge constraints.

                  2347.     Simultaneous Two-Channel Mice Brain Chemical Shift Imaging Using a 'standard' Biospec Spectrometer

Adrian Rengle¹, Hélène Ratiney¹, Sophie Cavassila¹, Olivier Beuf²

¹Université de Lyon, CREATIS-LRMN, CNRS UMR 5220; Inserm U630; INSA-Lyon; Université Lyon 1, Villeurbanne, France; ²Université de Lyon, CREATIS-LRMN , CNRS UMR 5220; Inserm U630; INSA-Lyon; Université Lyon 1, Villeurbanne, France

In the field of small animal spectroscopy, the interest for phased array coil is growing but high field MR experimental systems with multiple receiver channels are still rare. The configuration of a ‘standard’ 4.7T Bruker Biospec Avance II spectrometer was modified to allow simultaneous two-channel acquisitions. These modifications were used for two-channel mice brain chemical shifting imaging.

                  2348.     MEGA-Edited Detection of Metabolites with Coupled Spin-Systems: Simulations at High Field Strengths

Richard A E Edden¹, He Zhu^2,3, Peter B. Barker^2,3

¹Schools of Chemistry and Biosciences, Cardiff University, Cardiff, Wales, UK; ²Russell H Morgan Department of Radiology and, The Johns Hopkins University, Baltimore, MD, USA; ³FM Kirby Research Center for Functional MRI, Kennedy Krieger Institute, Baltimore, MD, USA

The MEGA-PRESS pulse sequence is increasingly being used for detection of compounds such as GABA, as well as more recently for distinguishing NAAG from NAA. High field systems (above 3T) are also becoming available, and promise improved SNR and chemical shift dispersion (in Hz), which should give improved editing performance. However, editing efficiency also depends on the evolution of spin-spin coupling modulation patterns, which are field strength dependent. This abstract presents results of spin system simulations for GABA, NAA and NAAG at field strenghts of 3, 7 and 9.4T.

                  2349.     Which Pulse Sequence Is Optimal for Myo-Inositol Detection at 3T?

Ileana Hancu¹

¹GE Global Research Center, Niskayuna, NY, USA

Repeatable and accurate myo-Inositol (mI) detection is important for diagnosing and monitoring multiple pathologic conditions of the brain. The performance of five classes of pulse sequences for mI detection was compared through simulations. These pulse sequences, which included a short TE PRESS, a Carr-Purcell PRESS sequence, an optimized STEAM sequence, an optimized zero quantum filter, and an optimized single quantum filter were compared to a standard PRESS TE=35ms pulse sequence. The simulations results, which were correlated with in vivo experimental data, indicated that the Carr-Purcell sequence offers the most reliable approach for mI measurements at 3T.

                  2350.     1H-MR Spectroscopy Utilizing a 1T Open MR System: Initial Clinical Results

Thomas G. Perkins¹, James B. Murdoch¹, Bryan Goss²

¹Philips Healthcare, Cleveland, OH, USA; ²New Mexico Cancer Center, Albuquerque, NM, USA

Proton MR Spectroscopy (1H-MRS) has been established for many years as a valuable tool in the study and diagnosis of neurological disorders, in particular for oncological follow-up of post-treatment brain tumors. Recently, 1T spectra were acquired on patients with normal brain chemistry to explore the clinical utility of 1H-MRS on a commercially available high field (1.0T) open MR system. Based on the success of this previous study, a clinical test is underway to evaluate the quality of spectra that can be obtained on patients with brain pathology within an oncology practice. Initial results of this study are presented here.

                  2351.     Single Echo Time Glutamate Editing at 3 Tesla

Yan Zhang¹, Stefano Marenco¹, Jun Shen¹

¹National Institute of Mental Health, Bethesda, M D, USA

A method for measuring glutamate using a single echo time without employing any spectrally selective pulses at 3 Tesla was proposed. By adding an additional slice-selective refocusing pulse into the PRESS sequence and optimizing echo time and inter-pulse delays, glutamate editing can be achieved in a single shot without using spectrally selective pulses which are susceptible to B0 inhomogeneity.

                  2352.     Reconstruction of NMR Spectra from Truncated Data with the Fast Pade Transform

Sun Kim¹, Glen Morrell²

¹School of Medicine, University of Utah, Salt Lake City, UT, USA; ²Radiology, University of Utah, Salt Lake City, UT, USA

MR proton spectroscopy with Fourier reconstruction requires long acquisition windows to allow sufficient spectral resolution to discriminate between metabolites of interest. The Fast Pade Transform (FPT) can be used to reconstruct NMR spectra from dramatically shortened acquisitions with no loss of spectral resolution. We investigate the use of the FPT for MR spectroscopy. We show that spectra reconstructed by FPT from repeated acquisitions of a short truncated FID have superior noise characteristics than spectra reconstructed from conventional long FID acquisitions by Fourier transform, given the same total acquisition time.

                  2353.     Degraded Water Suppression in 1H-MRS Due to Shimming; a Visualisation Method and a Comparison of Shimming Methods

Åsa Carlsson^1,2, Maria Ljungberg^1,2, Göran Starck^1,2, Eva Forssell-Aronsson^1,2

¹Radiation Physics, University of Gothenburg, Gothenburg, Sweden; ²Medical Physics and Biomedcial Engeneering, Sahlgrenska University Hospital, Gothenburg, Sweden

Shimming and water suppression are necessary to receive qualitative 1H-spectra. However, the global effects of locally optimised shim gradients might make the water suppression spatially selective and hence pose a risk of spurious echo artifacts. A method that visualise the spatially complex regions of unsuppressed water signal was designed and the impact of different shimming methods were compared. Even a large VOI, in a homogeneous region and linear shims resulted in a water suppression that did not cover the whole head. Higher order shims, a small VOI in a susceptibility influenced region left more than half of the head unsuppressed.

                  2354.     CSI Without Water Suppression at 3T

Grzegorz Lukasz Chadzynski¹, Uwe Klose¹

¹Neuroradiology, University Hospital, Tuebingen, Baden-Wuerttenberg, Germany

Proposed method offers spectra with sufficient quality for the quantification of the main metabolites (choline, creatine, NAA). Individual correction of the local resonant frequency can be performed even for a small voxels. This correction can be done by an evaluation of the water signal position. Moreover obtained CSI spectra do not need phase correction. Therefore it is possible to calculate a sum spectrum from a certain area which corresponds with certain anatomical structure. Such spectrum offers a higher SNR and better spectral resolution than SVS spectrum.

                  2355.     ³¹P Magnetization Inversion Transfer Study of Three-Site PCr←→ATP←→Pi Exchange System in Human Brain at 7T

Fei Du¹, Wei Chen¹

¹Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA

Magnetization inversion transfer (IT) NMR approach has been used for the studies of creatine kinase (CK) in human and animals. To date, IT approach was based on the two-site chemical exchange model and ATPase reaction was ignored. However, in principle, the chemical reactions of CK and ATPase constitute a three-site chemically coupled spin system i.e. PCr&[larr]&[rarr]ATP&[larr]&[rarr]Pi. In this work, we investigated the kinetics involving PCr&[larr]&[rarr]ATP&[larr]&[rarr]Pi in the human brain at 7T using the three-site chemical exchange model with full matrix Bloch equation analysis developed by our lab, and compared the results derived from the three-site and two-site chemical exchange model, respectively. This study reveals that CK reaction can be approximately treated as a two-site chemical exchange system when the ATPase reaction pool is relatively small. However, ATPase reaction must be treated as a three-site chemical reaction system in order to accurately measure its chemical reaction fluxes in the brain.

                  2356.     Adiabatic L-COSY at 7T

Saadallah Ramadan¹, Eva-Maria Ratai², Ovidiu C. Andronesi², A Gregory Sorensen², Carolyn E. Mountford¹

¹Radiology, Brigham and Women's Hospital, Boston, MA, USA; ²Athinoula A. Martinos Center for Biomedical Imaging, 149 Thirteenth Street, Suite 2301 , Charlestown, MA, USA

In vivo Localized Correlation Spectroscopy (L-COSY, 90ss 180ss t1 90ss Acq) is a developing technique that enables researchers to un-scramble spectroscopic findings in a relatively narrow spectral bandwidth along a second dimension, and thus, facilitating analysis and improving reliability. Chemical shift artifact, high SAR, and B1 inhomogeneity are issues that must be addressed properly to improve outcome. We here present the first application of adiabatic-Localized-COSY (AL-COSY) where spatial selection and excitation along two orientations is achieved by two pairs of slice-selective adiabatic inversion pulses, thereby increasing bandwidth and reducing B1 sensitivity.

                  2357.     Cross Peak Enhancement in Constant-Time COSY (CT-COSY)

Saadallah Ramadan¹, Carolyn E. Mountford¹

¹Radiology, Brigham and Women's Hospital, Boston, MA, USA

In vivo Localized Correlation Spectroscopy (L-COSY, 90ss 180ss t1 90ss Acq) is a developing technique that enables the researcher to un-scramble spectroscopic finding is a relatively narrow spectral bandwidth along a second dimension, and thus, facilitating analysis and improving reliability. However, when diagonal peaks are prominent, they can interfere with weak cross peaks. We propose here a CT-COSY method by which the amplitude of cross peaks can be improved and that of diagonal peaks reduced when the time delay between the leading 90^o and terminal 90^o increases. Theoretical reasoning is presented as well as phantom and in vivo muscle data.

                  2358.     Phase-Sensitive Localized COSY (PS-LCOSY)

Saadallah Ramadan¹, M Albert Thomas²

¹Radiology, Brigham and Women's Hospital, Boston, MA, USA; ²Radiology and Psychiatry, David Geffen School of Medicine, Los Angeles, CA, USA

Two-dimensional (2D) localized correlation spectroscopy (L-COSY) uses three slice-selective radio-frequency pulses (900ss-1800ss-900ss) for VOI localization and coherence transfer. One of the drawbacks of L-COSY is the twisted line shapes leading to inability in resolving the cross peaks close to the diagonal of the 2D spectrum. It has been demonstrated in high resolution NMR that phase-sensitive (PS) LCOSY minimizes the twisted line shapes and enhances resolution in the direct (F2) and indirect (F1) dimensions when compared to its magnitude counterpart (4). The first application of localized phase-sensitive homonuclear correlated spectroscopy (PS-LCOSY) using a whole body MRI scanner is presented.

                  2359.     Estimating Saturation Factors for PRESS with Inhomogeneous B1 at 7T

Douglas Kelley¹, Esin Ozturk-Isik², Janine Lupo²

¹Applied Science Laboratory, GE Healthcare, San Francisco, CA, USA; ²Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA

B1 inhomogeneity and increasing T1 values in vivo at 7T produce unwanted signal variation in PRESS. Calculation of PRESS saturation factors due to B1 inhomogeneity at 7T allows for assessment of appropriate acquisition timing and, given knowledge of metabolite T1 relaxation times, correction of signal variation for uncoupled spins like NAA, choline and creatine.

                  2360.     Improved 3D PRESS MRSI at 7T Using B1 Field Mapping and Optimization of Transmit Gain

Esin Ozturk-Isik¹, Janine M. Lupo¹, Sarah J. Nelson^1,2, Doug Kelley³

¹Radiology and Biomedical Imaging, UCSF, San Francisco, CA, USA; ²UCSF/UCB Joint Graduate Group in Bioengineering, San Francisco, CA, USA; ³GE Healthcare, San Francisco, CA, USA

This study aims at implementing a method to reduce the B1 inhomogeneity effects in 3D PRESS MRSI at 7T. Two GRE images with flip angles of 20° and 40° were acquired and the double angle method was used to estimate the B1 field factors. The transmit gain for the PRESS MRSI was optimized using the transmit gain and the flip angle of the GRE sequence and the measured B1 field factors. This method resulted in a more uniform flip angle distribution, improved spectral peak definition and lower lipid contamination across the PRESS box volume.

                  2361.     Interference of Fluorinated Anesthesia on 19F MRS of Fluorinated Drug Metabolism in Liver

Marcela Cortes-Ramirez¹, Giuseppe Pizzorno^1,2, Gopalkrishna Veni³, H Michael Gach^2,3

¹Drug Development, Nevada Cancer Institute, Las Vegas, NV, USA; ²University of Nevada School of Medicine, NV; ³Research Imaging Facility, Nevada Cancer Institute, Las Vegas, NV, USA

Fluorine (19F) magnetic resonance spectroscopy (MRS) can monitor the metabolism of fluorinated drugs like capecitabine in vivo. Fluorinated inhalation anesthetic agents like isoflurane are very useful since they can be safely administered for long experimental times typical of MRS animal studies. There is concern that fluorinated anesthesia may interfere with 19F MRS of capecitabine metabolism. We compared the effects of isoflurane and ketamine on capecitabine liver metabolism in C57BL/6J mice using 19F MRS. The isoflurane spectra did not interfere with the capecitabine and its metabolite spectra. However, ketamine appears to increase the rate of capecitabine liver metabolism compared to isoflurane.

                  2362.     Diffusion Measurement of Mobile Lipids Using Co-Resonant Coupled Metabolite Dephasing

Gerd Melkus¹, Philipp Mörchel¹, Michael Flentje², Peter Michael Jakob^1,3

¹Experimental Physics 5, University of Würzburg, Würzburg, Germany; ²Radiation Oncology, University of Würzburg, Würzburg, Germany; ³Research Center for Magnetic Resonance Bavaria (MRB), Würzburg, Germany

A frequency selective spin-echo method for Mobile Lipids (ML) detection in the 0.5-2.5 ppm area is presented where an additional selective pulse on the lactate and alanine methine (CH) groups minimizes the lactate and alanine methyl (CH₃) contamination to the ML signal. The metabolite signal dephasing is based on their J-coupling and is therefore independent of relaxation times. Pulsed field gradients were applied for diffusion measurement of the ML. The method was tested on a lactate/alanine and oil phantom. Diffusion weighted measurements of lactate free ML signal at ~1.3 ppm were successfully accomplished on xenograft tumor models.

                  2363.     Dealing with RF in MR Spectroscopy of the Human Breast at 7T

Dennis Klomp¹, Cecilia Possanzini², Bart van de Bank¹, Vivian Timmers², Alexander Raaijmakers³, Vincent Boer¹, Peter Luijten¹

¹Radiology, University Medical Center Utrecht, Utrecht, Netherlands; ²Philips Medical Systems, Best, Netherlands; ³Radiotherapy, University Medical Center Utrecht, Utrecht, Netherlands

MRS of the human breast is challenging, especially when tumor sizes are small and substantial lipid contents are included in the suspected voxel. At 7T, the sensitivity may improve, but due to expected non uniformities in B1 fields, lipid suppression becomes even more challenging. In this study we demonstrate the use of a B1 optimized RF coil in combination with a semi LASER sequence with MEGA water and lipid suppression to enable the detection of ultra low concentrations of choline pools in vivo.

                  2364.     Cortical Bone Water Studied with ¹H and ²H Double-Quantum Filtered NMR

Henry H. Ong¹, Felix W. Wehrli¹

¹Laboratory for Structural NMR Imaging, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

NMR and MRI are powerful tools for non-destructive study of bone water, which can provide insight into bone micro- and nanostructure. However, the MR signal of bone is comprised of several proton populations including collagen, collagen-associated water, and water within the Haversian and lacuno-canalicular system. Double-quantum filtered (DQF) NMR may be useful for characterizing the collagen-associated water contribution to the overall MR signal. Here, we studied lamb tibia cortical bone with ¹H and ²H in-phase DQF-NMR and report dipolar and quadrupolar splittings from bone, which we attribute to collagen backbone and collagen-associated water protons, respectively.

                  2365.     Improving the Spectral Quality of Magnetic Resonance Spectroscopy Using Multi-Taper Methods (MTM)

Shang-Yueh Tsai¹, Stefan Posse^2,3, Fa-Hsuan Lin^4,5

¹Department of Electrical Engineering, Chang Gung University, Tao Yuan, Taiwan; ²Department of Neurology, University of New Mexico School of Medicine, Alberquerque, NM, USA; ³Department of Electrical & Computer Engineering, University of New Mexico , Alberquerque, NM, USA; ⁴MGH-HMS-MIT Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; ⁵Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan

A Multi-Taper Method (MTM) is proposed to improve the spectral quality of the in vivo MRS data. The MTM are designed to improve the estimation of spectrum and also minimize the spectral leakage, which has been applied to dynamic brain imaging such as EEG and MEG. We showed that MTM improves the SNR while decrease the FWHM of MR spectrum and it is beneficial for the metabolic quantification for the in vivo SVS and PEPSI data. In conclusion, MTM has been successfully introduced for quantitative in vivo MRS. SNR and FWHM can be optimized using 5 and 7 tapering functions in turn metabolites quantification using LCModel can be significantly improved

                  2366.     Phase-Rotation for Spectroscopic Motion Correction

Saadallah Ramadan¹, Eva-Maria Ratai², Ravi Seethamraju³, Carolyn E. Mountford¹

¹Radiology, Brigham and Women's Hospital, Boston, MA, USA; ²Athinoula A. Martinos Center for Biomedical Imaging, MGH, Boston, MA, USA; ³Siemens Medical Solutions Inc, Malvern, PA, USA

Spectral analysis depends heavily on enhanced peak resolution and narrow line widths. Increased line width due to motion can be a major source of error. Phase rotation was first developed to resolve the desired signal from undesired signal in localized spectroscopy. However, phase-rotation is also suitable for filtering out motion-effected signal in localized spectroscopy. In this work, in vivo experiments show that phase-rotation technique can be used to filter out motion-effected signal in spectroscopic examinations, to produce narrow-lined spectra. This is an improvement over phase cycling techniques that rely on data averaging in the time domain.

                  2367.     In-Vivo High-Resolution Magic Angle Spinning Proton MR Spectroscopy of Drosophila Melanogaster Flies as a Model System to Investigate Trauma, Innate Immunity and Aging

Valeria Righi^1,2, Dionyssios Mintzopoulos^1,2, Yiorgos Apidianakis^1,3, Ovidiu C. Andronesi^1,2, Laurence G. Rahme^1,3, A. Aria Tzika^1,2
1NMR Surgical Laboratory, MGH & Shriners Hospitals, Harvard Medical School, Boston, MA, USA; ²Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA; ³Molecular Surgery Laboratory, MGH & Shriners Hospitals, Harvard Medical School, Boston, MA, USA

We demonstrate biomarker profiles with high-resolution magic angle spinning proton MR spectroscopy (HRMAS H1 MRS) of live Drosophila melanogaster flies. Aged flies exhibited more lipids following trauma, indicating that older flies are susceptible to trauma-mediated lipid homeostatic perturbations. In contrast, even young but immunocompromised flies also exhibited increased lipids suggesting that trauma elicits age-dependent lipid homeostatic perturbation that may promote immune dysfunction. We propose for the first time that in vivo HRMAS H1 MRS of Drosophila melanogaster in a 14 tesla spectrometer is a feasible and valuable model system for spectroscopic investigations of trauma, innate immunity and aging.

                  2368.     In Vivo ¹³C MRS of Human Brain at 3T Using Stochastic Decoupling with a Proton Volume Coil

Shizhe Li¹, Yan Zhang¹, Shumin Wang¹, Maria Ferraris Araneta¹, Christopher Johnson¹, Robert Innis¹, Jun Shen¹

¹National Institutes of Health, Bethesda, MD, USA

Proton decoupling power can be significantly reduced by using [2-¹³C]glucose infusion and detecting label incorporation into carboxylic/amide carbons. With increased decoupling efficiency, proton decoupling can use a volume coil, which is convenient for studying many brain regions, e.g., the frontal lobe. Here we report ¹³C MRS of human brain that uses a short birdcage coil for proton decoupling. The decoupling power is significantly reduced and at the same level as in previous human brain ¹³C MRS studies using quadrature surface coils. Analysis of specific absorption rate using volume coil proton decoupling is also provided.

                  2369.     High-Resolution NMR Spectroscopy in Inhomogeneous Fields Via Intermolecular Multiple-Quantum Coherences Between Spin 1/2 and Quadrupolar Nuclei

Zhong Chen¹, Shuhui Cai¹, Song Chen¹

¹Department of Physics, Xiamen University, Xiamen, Fujian, China

A heteronuclear CRAZED pulse sequence was designed to detect high-resolution NMR spectra in inhomogeneous fields via intermolecular zero-quantum coherences (iZQCs) or intermolecular double-quantum coherences (iDQCs) between spin 1/2 and quadrupolar nuclei. It overcomes the difficulty of selective excitation in homonuclear CRAZED experiments when the chemical shifts of solvent and solute are close to each other. In the 1D spectrum extracted from the 2D data, chemical shifts, coupling constants, multiplet patterns, and relative peak areas are almost independent of the magnetic field inhomogeneity.

                  2370.     Improved Proton Spectroscopy at 7T Using Localized B₁ Calibration

Maarten J. Versluis^1,2, Hermien E. Kan^1,2, Wouter M. Teeuwisse^1,2, Andrew G. Webb^1,2

¹Radiology, Leiden University Medical Center, Leiden, Netherlands; ²C.J. Gorter Center for high field MRI, Leiden University Medical Center, Leiden, Netherlands

Large variations of tip angle within a slice can lead to suboptimal pulse power optimization using standard techniques which measure the average tip angle over a slice: this effect is especially pronounced at fields of 7 T and above. Here, we show a technique which performs a volume selective power optimization in less than 5 seconds, and automatically calibrates the pulses for subsequent spectroscopy scans. Using this technique, STEAM spectra were acquired in the brain and calf muscle, in each cases resulting in spectra showing a 20-45% increase in SNR compared to calibrating for the average tip angle over a slice.

                  2371.     Determination of Residual Dipolar Coupling in Skeletal Muscle of Upper Extremity

John Austin Vargo¹, Steven L. Lindauer¹, Raymond R. Raylman¹, Richard G. Spencer², M. Albert Thomas³, S. Sendhil Velan¹

¹Center for Advanced Imaging and Department of Radiology, West Virginia University, Morgantown, WV, USA; ²Magnetic Resonance Imaging and Spectroscopy Section, NIA, National Institutes of Health, Baltimore, MD, USA; ³Radiology, University of California  Los Angeles, Los Angeles, CA, USA

The skeletal muscle spectroscopy is very complex due to the presence of scalar couplings and residual dipolar couplings. It is very important to consider the effects of residual dipolar coupling as it can change the spectral pattern and relaxation times. We have determined the residual dipolar coupling between the creatine CH3 and CH2 along with J interactions in the closed / open fist positions of flexor digitorum profundus muscle of upper extremity by advanced 1D and 2D MRS approaches.

                  2372.     Identification of Urine Biomarkers for X-Ray Radiation in Mice Using NMR Spectroscopy

Congju Chen¹, David J. Brenner², Truman R. Brown¹

¹Department of Radiology, Columbia University, New York, USA; ²Center for Radiological Research, Columbia University, New York, USA

In the present work, we describe metabolomics for X-ray irradiation biodosimetry in a mouse model. To analyze the large number of metabolomes, we employed the high-throughput NMR technique. The results show that the X-ray exposure yields distinct urine metabolomic phenotypes in mice. Furthermore, the phenotype is dose-dependent and time-dependent. Based on the understanding acquired in this work, we will be in a position to initiate measurements of metabolomics "fingerprints" in humans who were exposed to radiation.

                  2373.     Relationship Between MRS NAA Concentration and DTI ADC Values

Nuran Tunc-Skarka¹, Wolfgang Weber-Fahr¹, Mareen Hoerst¹, Gabriele Ende¹

¹Department Neuroimaging, Central Institute of Mental Health, Mannheim, Germany

Diffusion tensor imaging and proton magnetic resonance spectroscopy (MRS) yield different parameters for characterizing the evolution of a demyelinazation in white matter disease. NAA is commonly believed to provide a marker of neuronal density. Diffusion tensor imaging may give information about the axonal impairment of the neurons by changes of the patterns of anisotropy, e.g. fractional anisotropy (FA) or apparent diffusion coefficient (ADC). In this we study estimated and compared FA and ADC within a spectroscopic single voxel evaluate a possible direct relationship between those different measurement methods of similar objective of investigation.

                  2374.     Inhibitory Effect of Carbonic Anhydrase Inhibitors on the De Novo Lipogenesis. a Study with ¹³C-NMR Spectroscopy

Abolghasem Mohammadi¹, Dieter Leibfritz¹

¹Institute of Organic Chemistry, University of Bremen, Bremen, Germany

Obesity is an increasingly serious problem for the health of the population. Inhibition of de novo lipogenesis (DNL) from carbohydrate in the mammalian organism is a new approach for treatment of obesity. This inhibition is based on the inhibition of carbonic anhydrases (CA) isozymes on the step of pyruvate carboxylation in mitochondria. Sulphonamide/ Sulphamate are carbonic anhydrase inhibitors (CAIs) and inhibit DNL. We examined the effect of CA inhibition on DNL in 3T3-L1 cells in the presence of various CAIs i.e., topiramate, ethoxyzolamide, and acetazolamide by means of ¹³C-NMR spectroscopy. In the presence of CAIs DNL was 25-30% reduced.

                  2375.     Tailoring Linear Response Equilibrium Spectroscopy of Cholesterol Esters

Rudolf Fritz Fischer¹, Sebastian Kozerke¹, Christof Baltes¹, Markus Rudin¹, Peter Boesiger¹

¹Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

The Linear Response Equilibrium Sequence (LRE) can be used as a time and energy efficient MR sequence for 1H-spectroscopy. In this study, we tailor the LRE sequence for cholesterol ester detection. Sequence intrinsic aliasing of sidebands can be suppressed by a change in the pulse pattern exciting a dual steady-state. In addition, a frequency selective water suppression module has been introduced into the LRE sequence. Measurements performed on a phantom filled with liquid cholesterol linoleate proved the performance of the new sequence elements.