Matthew David Blackledge¹, Nina Tunariu^1,2, Zaki Ahmed², Julie Hughes², Raquel Perez-Lopez^1,2, Dow Mu Koh^1,2, David J Collins^1,2, and Martin O Leach^1,2
1CRUK Cancer Imaging Center, Division of Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom, ²MRI, Royal Marsden Hospital, London, United Kingdom

We evaluate the potential utility of storing all imaging acquisitions from whole-body diffusion-weighted MRI (WBDWI) studies.  This provides the possibility of using weighted least-squares fitting to obtain maps of ADC uncertainty, invaluable to clinicians wishing to report confidence in ADC estimates.  Furthermore, we describe for the first time a novel post-processing technique that combines ADC and ADC uncertainty information into a single computed image: noise-corrected exponential WBDWI.  We demonstrate that this technique provides excellent contrast between bone metastases and background healthy tissue, but does not suffer from the same T2 shine-through and/or coil sensitivity artefact present in conventional DW-images.

Peter B Barker^1,2, Subechhya Pradhan¹, Yanqin Lin^1,3, Karisa C Schreck⁴, Doris D.M. Lin¹, Jaishri Blakeley^4,5, and Roy E Strowd^5,6
1Radiology, Johns Hopkins Univ School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Department of Electronic Science, Xiamen University, Xiamen, China, People's Republic of, ⁴Neurology, Johns Hopkins Univ School of Medicine, Baltimore, MD, United States, ⁵Oncology, Johns Hopkins Univ School of Medicine, Baltimore, MD, United States, ⁶Department of Neurology and Internal Medicine, Wake Forest School of Medicine, Winston Salem, NC, United States

5 patients with high grade glioma were enrolled in an 8-week dietary therapy program based on the modified Atkin’s diet. Tumor and contralateral brain metabolism was monitored before and after therapy using proton MRS. Significant reductions in contralateral NAA were observed post treatment, as well as increases in acetone in both lesion and contralateral brain. MRS may be useful for monitoring the efficacy of dietary therapy in patients with malignant glioma. 

Sunitha B Thakur^1,2, Ralph Noeske³, Robert Young⁴, Justin Cross⁵, and Ingo Mellinghoff^6
1Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ³Berlin, Germany, ⁴Radiology, New York, NY, United States, ⁵Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁶New York, NY, United States

Isocitrate dehydrogenase IDH mutations in gliomas have ability to produce R-2-hydroxyglutarate (2HG). Directly measuring 2HG using non-invasive MR spectroscopy is an attractive strategy to accurately predict IDH mutation status and provide useful diagnostic and prognostic information. Quantification of 2HG metabolite may have potential advatages to evaluate treatment response in IDH1/2 targeted inhibitor trails . Here we report the optimization of subecho times on GE 3T scanners using phantoms to detect 2HG with the maximum sensitivity. We also evaluated the effect of different refocusing pulses on 2HG sensitivity with and without outer volume suppression (OVS) pulses. Part of these results were also verified with in-vivo data. 

Russell Rockne¹, Syed Rahmanuddin^1,2, John J. Park², and Jinha M. Park^2
1Dept. of Information Sciences/ Mathamatical Oncology, Beckman Research Institute City of Hope, Duarte, CA, United States, ²Radiology, Helford Clinical Research Hospital | Beckman Research Institute, Duarte, CA, United States

The purpose of this study is to evaluate changes in tumor volume and mean ADC before and after 90-yttrium (Y90) radioembolization for patients with metastatic liver cancer. Eighteen patients were identified in a retrospective study. Volumetric analysis of lesions before and after therapy showed a consistent increase in ADC (p<0.001), suggesting a decrease in cellularity. Changes in tumor volume measured on post-gadolinium (PG)  T1 MRI were not statistically significant. Additional MRIs following Y90 treatment should be analyzed with clinical outcomes to determine whether early changes in ADC following therapy may serve as an early indicator of response. 

Yu Gao^1,2, Yingli Yang³, Novena Rangwala¹, and Peng Hu^1,2
1Radiological Sciences, University of California, Los Angeles, Los Angeles, CA, United States, ²Physics and Biology in Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ³Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, United States

DWI is a promising imaging biomarker for tumor response evaluation, and the purpose of this work is to develop a distortion-free DW sequence that is reliable for adaptive treatment planning. ADC accuracy of our proposed diffusion-prepared segmented bSSFP-based sequence against the standard spin-echo single-shot echo-planar-imaging was quantitatively validated on a diffusion phantom. Geometric reliability was confirmed on both phantom and in-vivo experiments. Preliminary patient study on a MRI-Guided radiotherapy system showed high geometric accuracy and promising tumor detection capability. All these demonstrate the feasibility of using the DW-SSFP sequence for longitudinal tumor response evaluation and treatment planning. 

Qingjun Wang¹, Yong Guo¹, Jing Zhang¹, Minghua Huang¹, Qinglei Shi², and Tianyi Qian^2
1Radiology, Chinese Navy General Hospital, Beijing, China, People's Republic of, ²Scientific Marketing, Siemens Healthcare, Beijing, China, People's Republic of

In this study, we evaluated the advantages of using high b-value high-resolution diffusion-weighted MR imaging (DWI) to differentiate between malignant and benign thyroid nodules. This prospective study included 28 consecutive patients with thyroid nodules (14 malignant nodules in 10 patients and 24 benign nodules in 20 patients). Three b-values including b-values of 0, 800 and 2000 sec/mm² and a Readout Segmentation Of Long Variable Echo-trains (RESOLVE) imaging technique were used in the high b-value high-resolution DWI. The results showed that the high b-value high-resolution DWI can further increase the diagnostic accuracy for thyroid nodules with the best sensitivity, specificity and area under receiver operating characteristic curve (AUC) than low b-value or single high b-value.

Yoshiharu Ohno^1,2, Yuji Kishida², Shinichiro Seki², Hisanobu Koyama², Kota Aoyagi³, Hitoshi Yamagata³, Takeshi Yoshikawa^1,2, Masao Yui³, Yoshimori Kassai³, Katsusuke Kyotani⁴, and Kazuro Sugimura^2
1Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Japan, ²Radiology, Kobe University Graduate School of Medicine, Kobe, Japan, ³Toshiba Medical Systems Corporation, Otawara, Japan, ⁴Center for Radiology and Radiation Oncology, Kobe University Hospital, Kobe, Japan

    Recurrence assessment is very important for management of postoperative non-small cell lung cancer (NSCLC) patients.  We hypothesized that whole-body PET/MRI and MRI with DWI have a potential for improving recurrence assessment as compared with whole-body PET/CT and conventional radiological examinations in NSCLC patients.  The purpose of this study was to directly compare the diagnostic performance for postoperative lung cancer recurrence assessment among whole-body PET/MRI, MRI with and without DWI, PET/CT and conventional radiological examination in NSCLC patients.

Benjamin C Rowland¹, Min Zhou¹, Huijun Liao¹, Nils Arvold², Raymond Y Huang³, and Alexander P Lin^1
1Centre for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States, ²Radiation Oncology, Brigham and Women's Hospital, Boston, MA, United States, ³Radiology, Brigham and Women's Hospital, Boston, MA, United States

MR spectroscopy is a powerful technique for understanding tumour metabolism. Chemical shift imaging allows spatial variations in spectra to be observed at the cost of signal to noise and acquisition time. In this abstract we examine the heterogeneity of metabolite concentrations in both tumour and healthy tissue, in particular the onco-metabolite 2-hydroxyglutarate, to ascertain if the benefits of CSI outweigh the penalties.

Ben Babourina-Brooks¹, Sarah Kohe¹, Andrew Peet¹, and Nigel Davies^2
1University of Birmingham, Birmingham, United Kingdom, ²University Hospitals Birmingham, Birmingham, United Kingdom

The rate of improvement in survival, among children with brain tumours, has decreased in recent years and novel prognostic markers that may contribute to treatment stratification and improved outcomes are required.  Medulloblastoma tumours have a high rate of mortality due to their aggressive nature,  however some do not. MRS can measure absolute water proton resonance frequency (PRF), which is sensitive to temperature and other features of the tumour microenvironment. This could be utilized as a potential prognosis marker, however has not been explored. This study assessed the water PRF as a predictor of survival in a medulloblastoma patients, using MRS at diagnosis. 

Katarzyna Pierzchala¹, Nicolas Kunz¹, and Rolf Gruetter^1
1CIBM, EPFL, Lausanne, Switzerland

There is increasing need of a more human cell model to recapitulate the in-vivo cell-cell interactions, presenting physiological relevance. Magnetic resonance spectroscopy (MRS) has the potential to diagnose many tumors and to characterize their metastatic potential. In this study we present the metabolic profile of highly metastatic human melanoma cells line WM793.We demonstrate the feasibility of characterizing in-vitroliving melanoma cells by 1H-MRS with a total number of 9 metabolites quantified, covering energy markers (Glc, Lac, Ace), amino acids (Glu, Ala) and anti-oxidant (Tau, Asc) and cell membrane precursor (Cho).

Lin Cheng¹, Matthew D. Blackledge¹, David J. Collins¹, Nina Tunariu^1,2, Neil P. Jerome¹, Matthew R. Orton¹, Veronica A. Morgan³, Martion O. Leach¹, and Dow-Mu Koh^1,2
1Division of Radiotherapy and Imaging, Cancer Research UK Cancer Imaging Centre, Institute of Cancer Research, London, United Kingdom, ²Radiology, Royal Marsden Hospital, London, United Kingdom, ³Clinical MRI Unit, Royal Marsden Hospital, London, United Kingdom

Disease heterogeneity in patients with malignant pleural mesothelioma (MPM) makes it challenging to characterise solid disease and assess response following treatment. Computed Diffusion-Weighted MRI (cDWI) provides improved contrast between disease and background tissues, and facilitates total disease segmentation. A mixture modelling of ADC and R2 with semi-automatic segmentation on the cDWI is proposed to assess disease heterogeneity in MPM, with demonstration of its utility on a paired pre/post-treatment dataset. The mixture modelling methodology successfully characterised disease heterogeneity for two MPM patients, and can provide additional quantitative functional disease response characterisation compared with using only a single parameter.

Soichiro Yoshida¹, Fumitaka Koga², Hiroshi Tanaka³, Hiroshi Fukushima², Yasukazu Nakanishi², Minato Yokoyama¹, Junichiro Ishioka¹, Kazutaka Saito¹, Yasuhisa Fujii¹, and Kazunori Kihara^1
1Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan, ²Urology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, Japan, ³Radiology, Ochanomizu Surugadai Clinic, Tokyo, Japan

We evaluated standardized apparent diffusion coefficient value (ADC ratio) by taking the ratio of the ADC of the cancer tissue (T-ADC) to that of the gluteus maximus (G-ADC) can be a biomarker for predicting histological grade under two different imaging conditions. Two independent bladder cancer cohorts including 107 and 47 patients were evaluated. There was a significant difference in T-ADC between the cohorts, but no significant difference in the ADC ratio was observed. The ADC ratio significantly correlated with grade, as was the T-ADC. The ADC ratio might serve as an inter-institutional biomarker for predicting histological grade of bladder cancer.

Rong Zhou¹, Puneet Bagga¹, Kavindra Nath¹, David Mankoff¹, Hari Hariharan¹, and Ravinder Reddy^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

We presented the very first evaluation of glutamate chemical exchange saturation transfer (GluCEST) MRI to detect pharmacodynamic effect of small molecule drugs that target cancer glutaminolysis pathway. Conversion of glutamine to glutamate is a rate limiting step along this pathway. Inhibition of this conversion leads to reduction of cellular glutamate concentration that can be detected by GluCEST in vivo and confirmed by ex vivo high resolution 1H MRS of tumor homogenates. 

Ramesh Paudyal¹, Praveen Venigalla², Jingao Li^2,3, Nadeem Riaz², Jung Oh Hun¹, David Aramburu Nuñez¹, Vaois Haztglou⁴, Yonggang Lu⁵, Joseph O Deasy¹, Nancy Lee², and Amita Shukla-Dave^1
1Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ³Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China, People's Republic of, ⁴Radiology, Memorial Sloan Kettering Cancer, New York, NY, United States, ⁵Radiation Oncology, Washington University, St louis, MO, United States

This study aims to characterize human papillomavirus (HPV) positive (+) oropharyngeal cancer (OPC) using intravoxel incoherent motion (IVIM) DW-MRI performed before and during chemo-radiation therapy. A consensus clustering algorithm based on the hierarchical clustering and Pearson correlation distance was performed using the weekly IVIM DW-MRI metrics of D, f and D*, total tumor volume and delivered radiation dose. It demonstrated the presence of two HPV+ clusters. A trend towards significant increase in D during the pre- and intra-treatment (week 3) IVIM DW-MR data suggested that patients in cluster 2 may benefit with use of less aggressive therapy. 

Benedikt Feuerecker¹, Christian Hundshammer¹, Christof Seidl², Alfred Morgenstern³, Frank Bruchertseifer³, Reingard Senekowitsch-Schmidtke¹, and Markus Schwaiger^1
1Department of Nuclear Medicine, Technische Universität München, Munich, Germany, ²Department of Obstetrics and Gynaecology, Technische Universität München, Munich, Germany, ³European Commission Joint Research Centre Institute for Transuranium Elements, Karlsruhe, Germany

In the light of up regulation of glycolysis in tumors of the Warburg type, hyperpolarized ¹³C-labeled metabolic tracers offer new possibilities to probe fast metabolic pathways in real-time. As such, we assessed therapy response of malignant cancer cells to alpha-lipoic acid and a ²¹³Bi-anti-EGFR-MAb with hyperpolarized [1-¹³C]-pyruvate. Our results point to the fact that treatment of LN18 glioblastoma cells with LPA resulted in decreased proliferation/viability and reduced lactate export. Beyond, we demonstrated that NMR of hyperpolarized [1-¹³C]-pyruvate proved to be adequate for monitoring the response of bladder carcinoma cells to treatment with a ²¹³Bi-anti-EGFR-MAb as indicated by elevated pyruvate turnover.

Yang Runze^1,2, Susobhan Sarkar², Daniel J Korchinski¹, Ying Wu¹, V Wee Yong^2,3, and Jeff F. Dunn^1,2
1Radiology, University of Calgary, Calgary, AB, Canada, ²Clinical Neuroscience, University of Calgary, Calgary, AB, Canada, ³Oncology, University of Calgary, Calgary, AB, Canada

Glioblastoma Multiforme (GBM) is the most aggressive brain cancer with an abysmal prognosis. It has been shown that monocytes can be activated to suppress GBM stem cells using Amphotericin B (Amp B). We propose that monocytes can be labeled using intravenous injection of ultra-small iron oxide nanoparticles (USPIO), which will allow us to detect a rapid treatment response. We showed that Amp B treated animals significantly decreased T2* compared to vehicles, showing the presence of USPIO within the tumor. This shows that USPIO can be an effective tool to monitor cancer therapies that stimulate innate immunity.

Navid Farr¹, Paolo Provenzano², Joshua Park³, Sunil Hingorani², and Donghoon Lee^3
1Department of Bioengineering, University of Washington, Seattle, WA, United States, ²Fred Hutchinson Cancer Research Center, Seattle, WA, United States, ³Department of Radiology, University of Washington, Seattle, WA, United States

Pancreatic cancer is a devastating disease with poor prognosis. Pancreatic tumor therapy has been ineffective in part because pancreatic tumors have a dense stroma inhibiting penetration of chemotherapeutic drugs into the tumor. We performed multi-parametric MRI at high resolution to noninvasively assess tumor progression and responses to effective treatment. We used T1 and T2 relaxation, diffusion, magnetization transfer effects along with 3 dimensional volume measurements to characterize the tumors. MR measurements were then compared with histopathological results.

Manijeh Beigi¹, Anahita Fathi Kazerooni¹, Mojtaba Safari¹, Marzieh Alamolhoda², Ahmad Ameri³, Shiva Moghdam⁴, Mohsen Shojaee Moghdam⁵, and Hamidreza Saligheh Rad^1
1Medical Physics and Biomedical Engineering, School of Medicine, Quantitative MR Imaging and Spectroscopy Group, Research Center for Cellular and Molecular Imaging, Institute for Advanced Medical Imaging, Tehran, Iran, ²Statistics, Shiraz University of Medical Science, Shiraz, Iran, ³Oncology, Shahid Beheshti University of Medical Science, Tehran, Iran, ⁴Oncology, Tehran, Iran, ⁵Payambaran Imaging Center, Tehran, Iran

Induction chemotherapy is an effective way to control subclinical metastasis in locally-advanced nasopharyngeal cancer patients. Diffusion-weighted MRI is a noninvasive imaging technique allowing some degree of tissue characterization by showing and quantifying molecular diffusion. Histogram analysis on ADC map could be carried out to reveal physiological alterations early after IC.  For this purpose, several quantitative metrics from ADC-map were explored to obtain the most accurate feature(s) as potential predictive biomarker for early response of the lymphnode to IC. If the outcome can be predicted at an early stage of the treatment, the patient could be spared from unnecessary treatment toxicity.  

Olya Stringfield¹, John Arrington², Solmaz Sahebjam³, and Natarajan Raghunand^1
1Cancer Imaging & Metabolism, Moffitt Cancer Center, Tampa, FL, United States, ²Radiology, Moffitt Cancer Center, Tampa, FL, United States, ³Neuro-Oncology, Moffitt Cancer Center, Tampa, FL, United States

In this ongoing phase 1 study, we are investigating combined pembrolizumab and bevacizumab therapy with hypofractionated radiotherapy in recurrent glioma. The objective of this work is to develop a non-invasive response assessment measure using multiparameter MRI (mpMRI) scans acquired as part of clinical care which may precede volumetric changes in response to therapy.

Sharmili Roy¹, Dennis Lai-Hong Cheong¹, Mary C. Stephenson¹, Trina Kok¹, Evelyn Laurens¹, Joshua D. Schaefferkoetter¹, John James Totman¹, Vicky Koh², Johann Tang², Joseph Ng², Jeffrey Low², and Bok Ai Choo^2
1A*Star-NUS Clinical Imaging Research Centre, Singapore, Singapore, ²National University Health System, Singapore, Singapore

Response assessment after radical radiation therapy (RT) is typically performed months post treatment completion due to confounding acute RT effects. This study presents feasibility and early results on the ability of PET/MRI in visualizing early tumor changes in the cervix even during RT. This could potentially provide actionable information for treatment modifications prior to the completion of standard of care.  

Lucy Elizabeth Kershaw^1,2, Andrew McPartlin^2,3, Ben Taylor⁴, Ananya Choudhury^2,3, and Marcel van Herk^2
1CMPE, The Christie NHSFT, Manchester, United Kingdom, ²Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom, ³Oncology, The Christie NHSFT, Manchester, United Kingdom, ⁴Radiology, The Christie NHSFT, Manchester, United Kingdom

In this pilot work, our aim was to measure plasma flow (F_p) and permeability-surface area product (PS) through the course of RT in prostate tumour and normal tissue to determine whether significant changes could be detected early in treatment.   We detected significant increases in F_p and PS during radiotherapy in this small patient group.

Sungheon Gene Kim^1,2, Eric Sigmund^1,2, Melanie Moccaldi^1,2, Thorsten Feiweier³, and Linda Moy^1,2
1Center for Advanced Imaging Innovation and Research, Radiology, New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, Radiology, New York University School of Medicine, New York, NY, United States, ³Siemens Healthcare GmbH, Erlangen, Germany

This study is to investigate the potential of the surface-to-volume ratio obtained from multiple diffusion times to measure mammary duct microstructural changes induced by hormonal variation. Seven premenopausal women were scanned twice using a stimulated-echo diffusion sequence; one in the follicular phase of the menstrual cycle and again in the luteal phase. In 6 out of 7 subjects, the surface-to-volume ratio measured with 69 and 173 ms was significantly reduced in the luteal phase compared to the follicular phase. The length scales obtained in our study are consistent with the duct diameters reported in previous ex-vivo studies.

Quincy van Houtum¹, Dennis D.W.J. Klomp¹, and Marielle M.E.P. Philippens^1
1Imaging, UMC Utrecht, Utrecht, Netherlands

In this study we investigate the transverse relaxation effects at 7T during the fixation process in rectal specimens as a preparation for 7T MRI validation of rectal tumor regression with pathology. T2 and T2* were measured every 2 hours during fixation process in six different pig recta. Images allowed mapping of relaxation time at high spatial resolution. The circular muscle showed a decrease of 25% in T2* whilst other tissues remained constant over time for both parameters. A T2* decrease of 25% is seen in the circular muscle of the rectal wall was noticed whilst other tissue-regions remained constant. High resolution and SNR allowed for anatomical delineation and measuring the change of transverse relaxation times.

Frederic Carsten Schmeel¹, Birgit Simon¹, Julian Alexander Luetkens¹, Frank Träber¹, Leonard Christopher Schmeel¹, Hans Heinz Schild¹, and Dariusch Reza Hadizadeh^1
1Department of Radiology, University Hospital Bonn, Bonn, Germany

Imaging-based response assessment to local interventional therapies is essential for further therapy decisions in patients with advanced malignancies.  Therefore, we investigated whether early post-therapeutic changes in diffusion-weighted MRI using quantifications of the apparent diffusion coefficient (ADC) could predict the outcome of patients with liver-dominant metastatic colorectal cancer after radioembolization with 90-Yttrium microspheres (RE). Uni- and multivariate survival analyses were performed comparing various variables with potential impact on overall survival. Our results reveal that an increase in the post-therapeutic minimal ADC remained the strongest and only independent predictor of overall survival shortly after radioembolization.

Preethi Subramanian¹, Jun Zhang², Shivangi Vora², Marc Gollub³, Deborah Schrag⁴, Xiangyu Yang⁵, Lawrence Schwartz⁶, and Michael V Knopp^7
1Radiology, The Ohio State University, Colu,bus, OH, United States, ²Radiology, The Ohio State University, Columbus, OH, United States, ³Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁴Dana Farber Cancer Institute, Boston, MA, United States, ⁵The Ohio State University, Columbus, OH, United States, ⁶Radiology, Columbia University, New York, NY, United States, ⁷Radiology - Wright Center of Innovation, The Ohio State University, Columbus, OH, United States

Quality Assurance Methodology for Multicenter Clinical Trials using MRI

Shun Kishimoto¹, Jeeva Munasinghe², Marcelino Bernardo¹, Hellmut Merkle³, Keita Saito¹, James B Mitchell¹, Jan Henrik Ardenkjaer-Larsen⁴, Peter L Choyke¹, and Murali Cherukuri^1
1NCI, Bethesda, MD, United States, ²NINDS, Bethesda, MD, United States, ³LFMI, Bethesda, MD, United States, ⁴GE Health Care, brondby, Denmark

Photoimmunotherapy (PIT) is a novel therapy for cancer treatment.  PIT combines a targeted antibody with the photon absorber, IR700, which, after exposure to near infrared (NIR) light induces highly selective tumor necrosis with almost no side effects to normal adjacent tissue. PIT is now in Phase I clinical trials in head and neck cancers.  Although NIR PIT can be highly effective, the size of the lesion does not immediately change and it may take several weeks for the tumor to completely respond anatomically.  Thus, detecting early therapeutic response in the absence of anatomic change is of interest. Here, we demonstrate the effects of NIR PIT on 13C magnetic resonance spectroscopy (MRS) in an animal model (EGFR positive A431 tumor) using 13C labeled hyperpolarized (HP) pyruvate and fumarate. Interestingly, the lactate-to-pyruvate ratio was almost unchanged, while the malate-to-fumarate ratio showed a significant difference in PIT treated tumors. This is explained by the difference of the bio distribution of these tracers.  Hyperpolarized 13C labeled fumarate MRS is a promising method for detecting early PIT mediated cell necrosis.

Sophie E. Heethuis¹, Lucas Goense^1,2, Peter S.N. van Rossum^1,2, Irene M. Lips¹, Richard van Hillegersberg², Jelle P. Ruurda², Marco van Vulpen¹, Gert J. Meijer¹, Jan J.W. Lagendijk¹, and Astrid L.H.M.W. van Lier^1
1Department of Radiotherapy, UMC Utrecht, Utrecht, Netherlands, ²Department of Surgery, UMC Utrecht, Utrecht, Netherlands

The aim of this study was to investigate whether intravoxel incoherent motion (IVIM) MRI could be a non-invasive alternative for dynamic contrast-enhanced (DCE) MRI for response prediction in patients with esophageal cancer. The feasibility of IVIM was researched, followed by a first comparison with DCE-MRI. It was found that non-rigid registration improved the fitting of the IVIM parameters significantly. Comparison of IVIM and DCE-MRI suggested an inverse relation between perfusion fraction and area-under-the-concentration curve (AUC).

AnithaPriya Krishnan¹, Carrie R. McDonald¹, Nikdokht Farid², Anders M. Dale^1,3, and Nathan S. White^1,3
1MMIL, Radiology, University of San Diego, La Jolla, CA, United States, ²Division of Neuroradiology, University of San Diego, La Jolla, CA, United States, ³Center for Translational Imaging and Precision Medicine, University of San Diego, La Jolla, CA, United States

Contrast enhancing (CE) volumes are unreliable in the pseudo-progression window post radiotherapy and ADC based estimate of tumor cellularity is significantly affected by edema. Here, we provide preliminary evidence that Restriction Spectrum Imaging (RSI) based tumor cellularity performs better than ADC, supplements structural volumes and is significantly predictive of overall survival (OS). The study also highlights the need for higher b values as the association of ADC (in CE) with outcomes was observed only when high b values were used for ADC estimation and with b=1500s/mm2, ADC in edema ROI was not independent of edema volume (r=0.7)

Quincy van Houtum¹, Marielle M.E.P. Philippens¹, Maarten M.S. van Leeuwen², Frank F.J. Wessels², and Dennis D.W.J. Klomp^1
1Imaging, UMC Utrecht, Utrecht, Netherlands, ²Radiology, UMC Utrecht, Utrecht, Netherlands

The aim of this study is to demonstrate high resolution MR imaging of ex vivo pancreas-specimen while maintaining the in vivo shape and orientation. A pancreaticoduodenal specimen was positioned inside a 3T MRI while maintaining in vivo shape and orientation using substitutes for anatomical features. A 3D TSE sequence with a spatial resolution of 0.45x0.45x2mm, was used for acquisition.  Images showed contrast between multiple anatomical structures, allowed for discrimination between tumor and healthy tissue and showed an underestimation of tumor size on CT. Image quality holds promise for improved guidance during PA and registration with in vivo MRI.

Andrew Leynes¹, Jaewon Yang¹, Dattesh Shanbhag², Sandeep Kaushik², Florian Wiesinger³, Youngho Seo¹, Thomas Hope¹, and Peder Larson^1
1University of California San Francisco, San Francisco, CA, United States, ²GE Global Research, Bangalore, India, ³GE Global Research, Munich, Germany

The current clinical standard for extracranial MR-based attenuation correction (MRAC) on hybrid PET/MRI systems is the use of a Dixon-type sequence to generate a continuous-value fat-water map. The exclusion of bone in Dixon MRAC contributes a clinically significant amount of underestimation in bone lesion uptake. Bone information from a zero echo-time (ZTE) MRI pulse sequence is combined with the Dixon MRAC to produce a hybrid ZTE-Dixon MRAC. The work demonstrates, using PET/MR patient data, that the Dixon MRAC (neglecting bone) is underestimating bone lesion uptake by a clinically significant amount (>10%) when compared to the hybrid MRAC (including bone).

Ya-Fang Chen¹, Hsiang-Kuang? Liang², and Wen-Chau Wu^3,4
1Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan, ²Radiation Oncology, National Taiwan University Hospital, Taipei, Taiwan, ³Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan, ⁴Clinical Medicine, National Taiwan University, Taipei, Taiwan

In the present study, we investigated the feasibility of hybrid intravoxel incoherent motion and diffusion kurtosis MR imaging in assessing brain gliomas. Our data showed that combined intravascular fraction (a surrogate measure of cerebral blood volume), diffusion coefficient (a measure of diffusivity), and diffusion kurtosis coefficient (a measure of diffusion heterogeneity) may better demarcate brain gliomas through exploration of multiple pathophysiological aspects.

Marco Armbruster¹, Dominik Nörenberg¹, Katharina Hoffmann², Joachim Andrassy², and Harald Kramer^1
1Department of Clinical Radiology, Ludwig-Maximilian-University Munich, Munich, Germany, ²Department of Visceral Surgery, Ludwig-Maximilian-University Munich, Munich, Germany

Size measurements of hepatocellular carcinoma lesions play an important role in treatment algorithms of this disease, however little is known about which MRI sequence has the highest accuracy. This study shows, that there is a significant variance in size assessment of different MRI sequences and phases, while the hepatobiliary-phase seems to be best correlated to histopathologic measurements as the standard of reference and delineates HCC lesions most sharply.

Matthew David Blackledge¹, Christina Messiou^1,2, Jessica M Winfield^1,2, Dow Mu Koh^1,2, David J Collins^1,2, and Martin O Leach^1,2
1CRUK Cancer Imaging Center, Division of Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom, ²MRI, Royal Marsden Hospital, London, United Kingdom

We compare two enhancement fraction parameters that may be used for quantification of two-point contrast-enhanced MRI studies: The relative enhancement and the fractional enhancement. Using computer simulations we show that fractional enhancement is better behaved in the presence of imaging noise, resulting in better SNR for this parameter over a range of intrinsic longitudinal tissue relaxivities and contrast medium concentrations.  Further, in a cohort of 25 patients with retroperitoneal sarcoma, fractional enhancement significantly outperformed the relative enhancement in terms of visual assessment of contrast-to-noise, signal-to-noise, tumour detection, imaging artefacts and within tumour contrast.

Timothy James Pengilley Bray¹, Saurabh Singh¹, Arash Latifoltojar¹, Kannan Rajesparan¹, Farzana Rahman¹, Alan Bainbridge², Shonit Punwani¹, and Margaret A Hall-Craggs^1
1Centre for Medical Imaging, University College London, London, United Kingdom, ²Medical Physics, University College London, London, United Kingdom

Dixon imaging is becoming more widely used in multiple myeloma (MM) and can provide both functional and anatomical information. We observed that myeloma lesions seemed more conspicuous on fat only (FO) images than on conventional in-phase T1, and therefore hypothesised that lesion detection rates would be higher on FO images. In this research, we show that reader sensitivity, positive predictive value and confidence are indeed higher on FO images. This may be because myeloma lesions cause a proportionately greater change in fat content than in water content. We suggest that Dixon imaging should be used in preference to T1 imaging alone when performing WB-MRI. 

Naseer Ahmed¹, Tedros Bezabeh^2,3, Renelle Myers ⁴, Omkar B Ijare³, Shantanu Banerji ¹, Reem Alomran ¹, Zoann Nugent ¹, and Zoheir Bshouty ^4
1CancerCare Manitoba, Winnipeg, MB, Canada, ²Chemistry, University of Guam, Mangilao, Guam, ³Chemistry, University of Winnipeg, Winnipeg, MB, Canada, ⁴Health Sciences Centre, Winnipeg, MB, Canada

We undertook this study to determine if ¹H Magnetic Resonance Spectroscopy (MRS) can provide an alternate tool for the screening of lung cancer. Metabolic profiles of sputum and exhaled breath condensate (EBC) samples were obtained from 15 patients (cancer, n=8 and control, n=7) using a Bruker Avance 400 MHz NMR spectrometer. Methanol was detected at a significantly lower concentration in the EBC samples (p<0.05). Absence of glucose and lower concentration of glycoprotein (p<0.05) were observed in the sputum samples of the cancer patients. MRS may serve as a screening tool for lung cancer in high-risk patients but this requires validation in a larger study. 

Peng Sun¹, Kim J. Griffin¹, Hung-Wen Kao^2,3, Chien-Yuan Eddy Lin^4,5, Ching-Po Lin^3,6, and Sheng-Kwei Song^1
1Radiology, Washington University in St. Louis, St. Louis, MO, United States, ²Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ³Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ⁴GE Healthcare, Taipei, Taiwan, ⁵GE Healthcare MR Research China, Beijing, China, People's Republic of, ⁶Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan

Patients with brain tumors usually exhibit heterogeneous tissue features. Our results suggest DBSI-derived indices can quantify each individual feature. In addition, DBSI-derived tractography can visualized white matter tracts through confounding tumor and peritumoral edema.

Tae-Hoon Kim¹, Chang-Won Jeong¹, Jong-Hyun Ryu¹, Hong-Young Jun¹, Dong-Woon Heo¹, Sung-Chan Kang¹, and Kwon-Ha Yoon^1,2
1Imaging science-based research center, Wonkwang University School of Medicine, Iksan, Korea, Republic of, ²Radiology, Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan, Korea, Republic of

In this paper, we developed the quantification software for evaluating the voxel-based cellular heterogeneity of gadoxetic acid-enhanced magnetic resonance imaging (MRI) in the liver. Our software is clinically applied to accurately quantify and interpret the alterations of liver functions in patients with hepatocellular carcinoma.

Yin Xi¹, Qing Yuan¹, Yue Zhang¹, Ananth Madhuranthakam^1,2, Jeffrey Cadeddu³, Vitaly Margulis³, James Brugarolas^4,5, Payal Kapur^3,6, and Ivan Pedrosa^1,2
1Radiology, UTSouthwestern Medical Center, Dallas, TX, United States, ²Advanced Imaging Research Center, UTSouthwestern Medical Center, Dallas, TX, United States, ³Urology, UTSouthwestern Medical Center, Dallas, TX, United States, ⁴Internal Medicine, UTSouthwestern Medical Center, Dallas, TX, United States, ⁵Developmental Biology, UTSouthwestern Medical Center, Dallas, TX, United States, ⁶Pathology, UTSouthwestern Medical Center, Dallas, TX, United States

We propose a method that provides a simplified visual representation of tumor vascular heterogeneity in clear cell renal cell carcinoma (ccRCC) based on the combination of multiple parametric maps from quantitative dynamic contrast-enhanced (DCE) MRI analysis. Using this approach we observed an association between the tumor grade and vascular heterogeneity, especially in medium size tumors. A decision tree model was developed to predict high grade and low grade histology in solid ccRCCs, which may help in management decisions by providing additional information about the tumor biology beyond tumor size.

Stefan Hindel¹, Anika Söhner¹, Marc Maaß², and Lutz Lüdemann^1
1University Hospital Essen, Essen, Germany, ²Wesel Protestant Hospital, Wesel, Germany

We assessed the accuracy of interstitial volume fraction v(e) measurements in low-perfused tissue performed using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent. A 3D gradient echo sequence with k-space-sharing was used to determine v(e) in muscle tissue of twelve pigs. The evaluation was performed with the simple and extended Tofts model and the 2-compartment exchange model using different acquisition durations (ADs). The v(e) values determined by MRI were compared with the histologic analysis of muscle tissue sections. There was good agreement between histology and DCE-MRI modeling but also a strong dependence on AD with the Tofts models.

Ashley M Stokes¹, Jack T Skinner², and C. Chad Quarles^1
1Department of Imaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²National Comprehensive Cancer Network, Philadelphia, PA, United States

Dynamic susceptibility contrast (DSC-MRI) MRI is routinely used for brain tumor imaging and has shown promise as an early biomarker for treatment response. Conventional DSC-MRI is susceptible to contrast agent leakage effects, reducing the reliability of the resulting blood volume maps. The use of a simplified spin and gradient echo (SAGE) sequence, combined with robust processing strategies for correction of leakage effects, could facilitate more rapid clinical translation and adoption of DSC-MRI for brain tumor imaging. Taken together, the simplified SAGE approach and subsequence leakage correction provides a clinically feasible strategy for the simultaneous assessment tumor perfusion, permeability and cellularity. 

Stefan Hindel¹, Anika Söhner¹, Marc Maaß², and Lutz Lüdemann^1
1University Hospital Essen, Essen, Germany, ²Wesel Protestant Hospital, Wesel, Germany

We estimated the blood volume fraction in low perfused tissue using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The blood volume fraction v(b) was measured in hind leg muscle of pigs weighing approx. 60 kg. MRI was performed using a 3D gradient echo sequence with k-space-sharing and either a gadolinium-based (gadoterate meglumine) or an intravascular contrast agent (gadofosveset trisodium). Comparison of the different DCE-MRI methods with histology revealed good agreement between histological findings and the results obtained with the 2-compartment exchange model, bolus deconvolution and equilibrium MRI.

Soudabeh Kargar¹, Eric G Stinson², Eric A Borisch², Adam T Froemming², Akira G Kawashima³, Lance A Mynderse⁴, Joshua D Trzasko², and Stephen J Riederer^2
1Biomedical Engineering and Physiology, Mayo Graduate School, Rochester, MN, United States, ²Radiology, Mayo Clinic, Rochester, MN, United States, ³Radiology, Mayo Clinic, Scottsdale, AZ, United States, ⁴Urology, Mayo Clinic, Rochester, MN, United States

The use of MRI for planning targeted biopsy and evaluation of recurrence is becoming more common; in particular, Dynamic Contrast-Enhanced MRI (DCE-MRI) as part of multi-parametric MRI, is used for assessment of tumor angiogenesis and monitoring the effectiveness of therapy. We are interested in accurate estimation of K_trans and K_ep as an indication of change in perfusion patterns in benign and malignant tissue. We developed a robust and efficient numerical optimization technique to find the (nonlinear) least squares estimates of K_trans and K_ep from 3D DCE-MRI. The perfusion maps generated with this technique match the Levenberg Marquardt method and DynaCAD.

Natenael B. Semmineh¹, Kelly Gardner¹, Jerrold L. Boxerman², and C. Chad Quarles^1
1Imaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²Diagnostic Imaging, Rhode Island Hospital, Providence, RI, United States

Brain tumor DSC-MRI studies can be confounded by T₁ and T₂^* effects that occur when the contrast agent extravasates. Traditionally a combination of CA pre-loading and leakage correction techniques are used to minimize T₁ leakage effects, but currently there is no consensus on the most robust dosing scheme. Using simulations we demonstrate that pre-load dosing schemes significantly alter blood volume estimates. This computational approach is being utilized to identify a CA dosing scheme that minimizes total CA dose and yields robust CBV measures across a range of physical, physiological and pulse sequence parameters.

Georgios Krokos¹, Neil Thacker¹, Ibrahim Djoukhadar¹, David Morris¹, Alan Jackson¹, and Marie-Claude Asselin^1
1Medical and Human Sciences, University of Manchester, Manchester, United Kingdom

Variability in the underlying assumptions and mathematical formulations of the commonly used models for pharmacokinetic analysis of dynamic contrast-enhanced (DCE) MRI data make model selection not straightforward[1].  The variable noise in DCE-MR images affects the precision of parameters such that correcting the chi-square for the non-uniform noise is required for model comparison[2]. After noise correction, the two-compartmental exchange model fitted the data better, particularly in grade IV glioma, compared to the extended Tofts and adiabatic approximation to the tissue homogeneity models. Lengthening the acquisition duration not only provided more precise parameter estimates but also reduced the mathematical correlations between parameters.

Jan Novak^1,2, Stephanie Withey^1,2, Lesley MacPherson³, and Andrew Peet^1,2
1Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom, ²Oncology, Birmingham Children's Hospital, Birmingham, United Kingdom, ³Radiology, Birmingham Children's Hospital, Birmingham, United Kingdom

Low grade paediatric brain tumours are increasingly being targeted by anti-vasculature therapies.  It is therefore of particular interest to assess perfusion in these pathologies. We assessed paediatric tumour perfusion using both arterial spin labelling (ASL) and dynamic susceptibility contrast (DSC) on a 3T TX Philips Achieva scanner. Blood flow maps were produced for both techniques where good qualitative agreement was found illustrated by strong, significant pixel-by-pixel correlations.  We found that tumour blood flow measured by ASL and DSC significantly correlated (ρ = 0.714, P = 0.047) suggesting ASL can be used instead of DSC for this measurement.

Xiaoyan Meng¹, Xiao Chen¹, Yaqi Shen¹, Zhen Li¹, Xuemei Hu¹, Hui Lin², and Daoyu Hu^1
1raidology, Tongji hospital, Tongji medical college, Huazhong university of science and technology, Wuhan,Hubei province, China, People's Republic of, ²GE Healthcare, Wuhan,Hubei, China, People's Republic of

The aim of our study was to compare the accuracy of PDFF measurements and conventional IP/OP images for quantifying the fat content of adrenal gland nodules and for distinguishing adenomas from nonadenomas.Our results showed that PDFF imaging provided almost accuracy compared with IP/OP imaging.PDFF could be a simpler diagnostic tool for discriminating adenomas from nonadenomas, with a high sensitivity and a relatively high specificity, thus avoiding complicated data calculations. This technique is potentially a helpful and a widely applicable method for diagnosing adrenal gland nodules in clinical studies. 

Shu Xing¹, Carolyn R. Freeman², Sungmi Jung³, and Ives R. Levesque^4,5
1Physics, McGill, Montreal, QC, Canada, ²Radiation Oncology, McGill University Health Center, Montreal, Canada, ³Pathology, McGill University Health Center, Montreal, Canada, ⁴Medical Physics Unit, McGill University, Montreal, QC, Canada, ⁵Research Institute, McGill University Health Center, Montreal, QC, Canada

In this work, we propose a novel method to automatically distinguish various pathological tissue types within tumors, in particular soft tissue sarcoma. Pathological tissue signatures within the tumor, including high cellularity, high T₂ content, or necrosis, can be interpreted from the combination of T₂-weighted images, DW-MRI (b=500-1000 s/mm²) and ADC maps. We propose an automated approach that compares the ADC, the T₂, and a quantified surrogate for the high-b-value DW-MRI image, between the tumor and a reference tissue, to segment the tumor. Delineating tumor sub-regions is useful in assessing the overall tumor environment and may inform sub-region-targeted radiation dose-painting.

Miaomiao Wang¹, Chao Jin¹, Jianxin Guo¹, Lihong Chen¹, Tingting Qu¹, Hui Hao¹, and Jian Yang^1
1Department of Radiology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, People's Republic of

Quantitative characterizations of functional vascularity of ACTH-producing and non-functioning pituitary adenomas are critical to identify their differences in clinics. From this, a semi-quantitative method, i.e. three-time point method of DCE-MRI was proposed to detail the dynamic enhanced features and thus distinguish them. The results indicate that based on the enhancement time-signal curve, the volume percentage of the two groups are different in the washout-type curve. Particularly, in wash-out phase of the curve, the descending slope of ACTH-producing is greater than that in non-functioning pituitary adenoma.

Benjamin King Hong Law¹, Ann D King¹, Kunwar S Bhatia¹, Anil T Ahuja¹, Brigette B Ma², David Ka-Wai Yeung², Yi-Xiang Wang¹, and Jing Yuan^3
1Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, Hong Kong, ²Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong, ³Medical Physics and Research Department, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong

Amide proton transfer (APT) imaging is a promising functional MRI technique that investigates the chemical exchange processes between free water and mobile amide protons in cancers. It is sensitive to small variations in these amide protons but the potential value of APT imaging in head and neck cancer is unknown. We have shown APT imaging of head and neck cancer is feasible, although the success rate varies with tumour site. No difference was found between the APT parameters of undifferentiated nasopharyngeal carcinoma and head and neck squamous cell carcinoma in this small preliminary study, but larger studies are needed.

Mirabela Rusu¹, Elizabeth A. Morris², Elizabeth J. Sutton², and Ileana Hancu^1
1GE Global Research, Schenectady, NY, United States, ²Memorial Sloan Kettering Cancer Center, New York, NY, United States

Lesion identification in MR-guided biopsy exams can be hampered by many factors, including large deformations and limited tissue perfusion due to breast compression. Multiple post-contrast scans, image subtraction and maximum intensity projection map generation may be needed to relocate the lesion. This preliminary study suggests that non-rigid registration between the (uncompressed breast) pre-biopsy series and the (compressed breast) biopsy series may facilitate fast and accurate lesion (re)localization, even with limited/absent lesion enhancement. 

Jie Ding¹, Patricia A Thompson², Marilyn T Marron³, Maria Altbach^3,4, Denise Roe^3,5, Jean-Philippe Galons⁴, Cynthia A Thomson³, Fang Wang⁶, Alison Stopeck⁷, and Chuan Huang^1,8,9
1Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States, ²Pathology, Stony Brook Medicine, Stony Brook, NY, United States, ³Cancer Center, University of Arizona, Tucson, AZ, United States,⁴Medical Imaging, University of Arizona, Tucson, AZ, United States, ⁵Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, United States, ⁶Stony Brook Medicine, Stony Brook, NY, United States,⁷Hematology and Oncology, Stony Brook Medicine, Stony Brook, NY, United States, ⁸Radiology, Stony Brook Medicine, Stony Brook, NY, United States, ⁹Psychiatry, Stony Brook Medicine, Stony Brook, NY, United States

It has been shown that breast density (BD) value derived from fat-water-ratio MRI (FWR-MRI) strongly correlates with standard digital mammogram derived BD. The fact that no ionizing radiation is associated with FWR-MRI makes it a lower-risk modality for long term BD monitoring and clinical trials. However, data regarding the individual and group level variability and reliability of this method needs to be established.   Conventional approaches for FWR-MRI derived BD rely on manually drawn regions-of-interest. These processes are cumbersome and prone to measurement bias, which may limit the application of FWR-MRI derived BD. Automated breast segmentation has been proposed to resolve this problem and limited results to date are promising. Additional data including an evaluation of BD reliability from manual versus automated measurements is still needed.   In this study, we evaluate the test-retest reliability of the FWR-MRI derived BD and the quality of data using manual versus automated breast segmentation. Our results demonstrate the high reliability of the FWR-MRI derived BD measure, Fra80, with a typical error of less than 0.02 for both automated and manual breast segmentation. Moreover, our automated breast segmentation protocol yields more reliable Fra80 BD measures compared to the labor-intense manual segmentation method.

Subashini Srinivasan¹, Bruce L Daniel¹, and Brian A Hargreaves^1
1Radiology, Stanford University, Stanford, CA, United States

Pharmacokinetic (PK) models have been used to estimate physiological parameters such as permeability and dispersion of the contrast agent and is estimated using the acquired signal, pre-contrast T10, and the acquisition flip angle. In this work, we have determined the dependence of the dispersion models’ and Tofts models’ PK parameters on T10 and B1 maps, as well as the errors introduced by using constant T10 and B1 values in 11 biopsy-proven tumors. Our results show that PK parameters such as kep of Tofts model and kappa of mLDRW dispersion model are less dependent on T10 and B1 and could potentially be used with higher accuracy and precision even when T10 and B1 maps are not acquired.

David Naves Sousa¹, Filipa Borlinhas¹, and Hugo Alexandre Ferreira^1
1Institute of Biophysics and Biomedical Engineering, Faculdade de Ciências da Universidade de Lisboa, Lisboa, Portugal

Diffusion-Weighted Imaging is a MRI technique that is able to distinguish between benign and malignant breast tumours via the Apparent Diffusion Coefficient (ADC). Nevertheless, this parameter provides very limited information regarding tissue microstructure. Here, is presented an approach to estimate the intracellular (Di) and extracellular (De) diffusion coefficients, and cell membrane permeability of tumour tissues which makes use of known ADC values, histological images and Monte-Carlo simulations of diffusion processes. Results show that distinct combinations of (Di, De, P) correlate with tumour type, and that a decreased De was observed in malignant tumours in agreement with known extracellular matrix changes.

Marco Borri¹, Maria A. Schmidt¹, Julie C. Hughes¹, Erica D. Scurr¹, Kristiana D. Gordon^2,3, Peter S. Mortimer^2,3, Dow-Mu Koh¹, and Martin O. Leach^1
1CR-UK Cancer Imaging Centre, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom, ²Cardiac and Vascular Sciences, St. George’s, University of London, London, United Kingdom, ³Skin Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom

The pathophysiology of breast cancer related lymphoedema (BCRL) is not well understood, one of the main limiting factors being a lack of information on lymphatic collecting vessels. We have recently proposed a novel contrast-enhanced magnetic resonance lymphangiography protocol which allows the identification of lymphatics via the use of associated contrast uptake curves. In this work we have quantified differences between affected and unaffected arms in a cohort of patients with unilateral BCRL. Our analysis did not detect significant differences in vessel counts between the two sides within different sections of the forearm. However, there was a statistically significant difference in vessel diameter between the two arms; lymphatics within the affected arms presented with a larger diameter.

Lori R. Arlinghaus¹, Richard D. Dortch^1,2, Jennifer G. Whisenant², Hakmook Kang³, and Thomas E. Yankeelov^1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ³Department of Biostatistics, Vanderbilt University, Nashville, TN, United States

Magnetization transfer (MT) imaging is sensitive to changes in the macromolecular content of tissue and is, therefore, gaining increased attention as a noninvasive approach to probe the complex tumor environment in cancer. The ratio of macromolecular protons to the protons in the free water pool, or pool size ratio (PSR), can be quantified with quantitative MT (qMT) imaging and may be useful for detection of changes in macromolecular content early in the course of treatment. In this study, we explore the repeatability of PSR measurements in healthy breast fibroglandular tissue at 3T to serve as a benchmark for future longitudinal studies of breast cancer treatment.

Erwin Krikken¹, Moritz Zaiss², Vitaliy Khlebnikov¹, Hanneke W.M. van Laarhoven³, Dennis W.J. Klomp¹, and Jannie P. Wijnen^1
1Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ²Deutsches Krebforschungszentrum, Heidelberg, Germany, ³Medical Oncology, Academic Medical Center Amsterdam, Amsterdam, Netherlands

Neoadjuvant chemotherapy has an important role in the treatment of breast cancer and the need for early detection of treatment response is high. As a non-invasive method able to predict treatment response is lacking, we investigated the feasibility of using amide CEST MRI at 7T as a biomarker. Six patients were included after informed consent was given. The ATP signal was robust and repeatedly detectable in the same patient. Significant differences were seen in amide signal before  and after the first cycle of chemotherapy.

Jurgen H Runge¹, Jules L Nelissen^2,3, Larry de Graaf², Barbara Molenkamp⁴, Suzan van der Meij⁴, Klaas Nicolay², Gustav J Strijkers³, Jaap Stoker¹, Anneloes E Bohte¹, Aart J Nederveen¹, Ondrej Holub⁵, and Ralph Sinkus^5
1Radiology, Academic Medical Center, Amsterdam, Netherlands, ²Biomedical NMR, Eindhoven University of Technology, Eindhoven, Netherlands, ³Preclinical and Translational MRI, Academic Medical Center, Amsterdam, Netherlands, ⁴Surgery, Academic Medical Center, Amsterdam, Netherlands, ⁵Biomedical Engineering, King's College London, London, United Kingdom

Distinction between benign and malignant breast lesions remains difficult with conventional (dynamic) contrast-enhanced MRI. MR Elastography (MRE) can distinguish benign and malignant tissues based on their viscoelastic properties but breast MRE has not found widespread use in daily clinical practice, because of the complex equipment required and cumbersome data acquisition. Here we present a compact, easy to handle breast MRE set-up that allows the acquisition of high quality, artefact-free MRE data. This set-up was designed, built and tested at two different institutions in volunteers and a patient.

Bin Wu^1,2, Yanqiong Chen², Hui Liu³, Xu Yan³, Caixia Fu⁴, Dan Wang¹, Jian Mao², Dominik Nickel⁵, Berthold Kiefer⁵, Yajia Gu², and Weijun Peng^2
1Radiology, Shanghai Proton and Heavy Iron Center, Fudan University Caner Center, Shanghai, China, People's Republic of, ²Radiology, Fudan University Shanghai Cancer Center, Shanghai, China, People's Republic of,³NEA MR Collaboration, Siemens Ltd, Shanghai, China, People's Republic of, ⁴Siemens Shenzhen Magnetic Resonance Ltd, Shenzhen, China, People's Republic of, ⁵Siemens Healthcare GmbH, Erlangen, Germany, Forchheim, Germany

We investigated the clinical value of a dual-parameter classification method in differentiating benign and malignant breast lesions using readout-segmented diffusion-weighted imaging (RS-DWI) and quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and found they correlated with histological results.

Roberta M Strigel^1,2,3, Leah Henze Bancroft², Diego Hernando¹, and Scott B Reeder^{1,2,3,4,5,6
1}Radiology, University of Wisconsin, Madison, WI, United States, ²Medical Physics, University of Wisconsin, Madison, WI, United States, ³Carbone Cancer Center, University of Wisconsin, Madison, WI, United States,⁴Biomedical Engineering, University of Wisconsin, Madison, WI, United States, ⁵Emergency Medicine, University of Wisconsin, Madison, WI, United States, ⁶Medicine, University of Wisconsin, Madison, WI, United States

Elevated breast density confers an increased risk for breast cancer. Accurate and precise measurement of the amount of fibroglandular breast tissue has potential to serve as a quantitative imaging biomarker of risk for the development of breast cancer.  In this work we introduce novel, confounder corrected chemical-shift encoded (CSE)-MRI techniques to measure the proton density water fraction (PDWF). Estimation of PDWF with CSE-MRI addresses potential confounders that negatively impact accuracy, precision, and reproducibility, enabling protocol independent quantification of the volume and concentration of fibroglandular tissue in the breast.

Mariko Goto¹, Koji Sakai¹, Kayu Takezawa¹, Hiroshi Imai², Elisabeth Weiland³, and Kei Yamada^1
1Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan, ²Siemens Japan K.K., Tokyo, Japan, ³Siemens Healthcare GmbH, Erlangen, Germany

The prototype TWIST-VIBE sequence improves the temporal resolution of breast MRI while preserving spatial resolution. High-temporal resolution TWIST-VIBE was performed during the initial enhancement phase and high-spatial resolution routine DCE MRI in a single session, and whether the additional information of initial enhancement analysis using TWIST-VIBE improved the diagnostic accuracy of breast MRI was evaluated. The combination of BI-RADS and new parameters of initial enhancement (MS and TTE) calculated from TWIST-VIBE has the potential to increase the specificity of breast MRI and may be useful as additional information to determine the need for biopsy.

Yiqi Hu¹, Tao Ai¹, and Liming Xia^1
1Tongji Hospital, department of radiology, Wuhan, China, People's Republic of

The overlap of pharmacokinetic parameters values exists between benign and malignant lesions. Most previous studies chose mean pharmacokinetic parameters when elevating the state of breast lesions perfusion. However, tumors are heterogeneous that are marked by microenvironmental factors and thus manifests as radiologic heterogeneity. The mean pharmacokinetic parameter values may overlook the subtle but important difference between breast lesions. Thus, the aim of our study is to investigate the feasibility of histogram analysis of pharmacokinetic parameters including Ktrans, kep, ve in breast DCE-MRI imaging and determine which metric of each pharmacokinetic parameter may best help differentiate benign from malignant lesions.

Kayu Takezawa¹, Mariko Goto¹, Koji Sakai¹, Hiroyasu Ikeno¹, Katsuhiko Nakatsukasa², Hiroshi Imai³, and Kei Yamada^1
1Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan, ²Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan, ³Siemens Japan K.K, Tokyo, Japan

     The influence of fat suppression on T1 values and pharmacokinetic parameters in breast cancer were evaluated using a prototype Dixon-TWIST-VIBE technique. We measured T1 values of breast cancers on both fat suppression and not-fat suppression data sets and we calculated K^trans values using same ROI that employed on T1 value measurements. Our result suggests that the fat suppression might influence T1 values in breast cancer, and reliability of K^trans seemed inappropriate as an absolute value. On the other hand, the assessment of intra-patient K^trans change might be feasible.

Yoon Jung Choi¹, Jeon-Hor Chen^2,3, Shunshan Li², Po-Han Chen⁴, Pei-Yu Liu⁴, Inyoung Youn¹, and Min-Ying Su^2
1Department of Radiology, Kangbuk Samsung Hospital, Seoul, Korea, Republic of, ²Center for Functional Onco-Imaging, Department of Radiological Sciences, University of California Irvine, Irvine, CA, United States,³Department of Radiology, Eda Hospital and I-Shou University, Kaohsiung, Taiwan, ⁴Department of Medical Imaging, China Medical University, Taichung, Taiwan

Hormonal regimens may affect breast tissue with the change of breast volume or composition. This study was to apply a well-established breast and fibroglandular tissue segmentation method to analyze the density changes in patients receiving adjuvant hormonal therapy. The results showed that pre-menopausal women had a higher density reduction, presumably due to their more abundant fibroglandular tissues that can be decreased, but a high variation was observed. The density reduction assessed by 3D MRI may be used as a surrogate marker to correlate with metabolic genotyping, and further used in combination to better predict patient’s prognosis.

Leah C Henze Bancroft¹, Roberta M Strigel^1,2,3, Gavin Hamilton⁴, Scott B Reeder^1,2,5,6,7, and Diego Hernando^2
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Radiology, University of Wisconsin-Madison, Madison, WI, United States, ³University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, United States, ⁴Radiology, University of California, San Diego, San Diego, CA, United States, ⁵Medicine, University of Wisconsin-Madison, Madison, WI, United States, ⁶Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, ⁷Emergency Medicine, University of Wisconsin-Madison, Madison, WI, United States

The highly heterogeneous distribution of fat and fibroglandular tissue in the breast makes obtaining accurate measures of T1 and T2 relaxation times difficult.  Here, a rapid, multi echo, multi TR spectroscopy sequence is used to measure the T1 and T2 relaxation times of fat and fibroglandular tissue in the breast at 3T.  Partial voluming effects are accounted for through accurate measurement of the proton density fat fraction.

Neeti R Bagadiya¹, Laura Heacock¹, Yiming Gao¹, Meghan Jardon¹, Samantha Heller¹, and Linda Moy^1
1Radiology, New York University, New York, NY, United States

Breast MRI allows preoperative identification of patients who may have extensive disease at presentation and allows for appropriate surgical planning and treatment.   Despite the high sensitivity of MRI, the role of preoperative surgical staging of breast cancer patients is controversial. There is concern that the high false positive rates of breast MRI lead to additional biopsy procedures and surgeries [1,2]. Abbreviated breast MRI (AB-MR), defined as the first post-contrast scan, has been proposed as an exam that may have a higher specificity compared to conventional breast MRI  [3,4].  Two recent studies show that AB-MR has a high PPV for and may preferentially selects for biologically significant tumors, thereby reducing overdiagnosis and overtreatment. The concept of a biologically significant breast cancer has not been defined.  We hypothesized that since invasive carcinomas usually demonstrate fast initial uptake of contrast, a threshold of enhancement as determined by initial enhancement ratio (IER) may be associated with the identification of biologically significant breast cancers [5].  We evaluated a cohort of women with known cancer who underwent MRI guided needle localization (MRNL) for a finding that was suspicious for additional disease.  We examined whether there was an association with the IER and the likelihood that it would be detected on AB-MR exam.  Using Dynacad software we retrospectively reviewed the IER of MRI detected synchronous cancers that underwent MRNL.  We found there is a significant correlation between invasive cancers and IER that can aid in the detection of biologically significant synchronous cancers on MRI.