CEST Technologies & Molecular Applications of CEST
 

Monday 1 June 2015

Ding Xia¹, Joshua I. Friedman², Jae-Seung Lee^1,2, Ravinder R. Regatte¹, and Alexej Jerschow^2
1Department of Radiology, New York University Langone Medical Center, New York, NY, United States, ²Department of Chemistry, New York University, New York, NY, United States

NOE contamination of CEST signals is a frequently encountered problem. We present a method for the elimination of NOE contributions in CEST measurements via an exchange-rate filter. The method is demonstrated with raw egg sample.

Bing Wu¹, Han Ouyang², and Zhenyu Zhou^1
1GE healthcare China, Beijing, Beijing, China, ²China academy of sciences cancer hospital, Beijing, China

CEST acquisition is usually limited to single slice as different frequency saturations are played out which may interfere with adjacent slices. On the other hand, certain applications call for the need of a larger spatial coverage in slice direction due to the heterogeneity of the region of interest. An example could be glioma, which may be associated with edema that responses differently in APT measurement from the tumor. In this work, a slice multiplexed CEST acquisition is proposed, in which two or more slices that experience the same CEST saturation are simultaneously acquired.

Hua Li¹, Ke Li¹, Xiao-Yong Zhang¹, Zhongliang Zu¹, Moritz Zaiss², Daniel F. Gochberg¹, John C. Gore¹, and Junzhong Xu^1
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Department of Medical Physics in Radiology, DKFZ, Heidelberg, BW, Germany

Amide proton transfer (APT) imaging has been suggested as a surrogate biomarker of endogenous mobile proteins and peptides. However, conventional APT analyses using magnetization transfer asymmetry, may be significantly influenced by various confounding effects, such as MT, R1, and direct saturation. Previously reported R1 correction approaches are based on a simplified two-pool (water and amide protons) model. However, in biological tissues, water exists in multiple compartments. In this study, Gd-DTPA was introduced into tissue in order to selectively alter extracellular relaxation in tumors. By such a means, the accuracy of R1 corrections for APT imaging was evaluated in vivo.

Meiyun Wang¹, Erning Zhang¹, Carlos Torres², Yan Bai³, Xiaowei He⁴, Dapeng Shi³, Panli Zuo⁵, Michael T McMahon⁶, Benjamin Schmitt⁷, and Xiaolei Song^8
1Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, Henan, China, ²Department of Radiology, The Ottawa Hospital, The University of Ottawa, Ottawa, ON, Canada, ³Henan Provincial People's Hospital, Zhengzhou, Henan, China, ⁴School of Information Sciences and Technology, Northwest University, Xian, Shanxi, China, ⁵Siemens Healthcare, Beijing, China, ⁶Dept. of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ⁷Siemens Ltd Australia, Macquarie Park, Australia, ⁸Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

This study investigated the capability of a length and offset varied saturation (LOVARS) chemical exchange-dependent saturation transfer (CEST) imaging in early detecting intracerebral hemorrhage (ICH) and ischemia and proved that LOVARS can identify and separate ICH and ischemia at the early stage by demonstrating opposite LOVARS signals. Therefore the non-invasive LOVARS may be a new MRI technique for the diagnosis of early stroke and may improve stroke patient care.

Daniel James Clark^1,2, Alex K Smith^3,4, Michael V Knopp¹, and Seth A Smith^3,4
1Wright Center of Innovation, Department of Radiology, The Ohio State University, Columbus, OH, United States, ²Department of Biomedical Engineering, The Ohio State University, Columbus, OH, United States, ³VUIIS, Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ⁴Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

In this study we show that a variable RF pre-saturation power CEST scheme (vCEST) is feasible in vivo. Agar gel phantoms with glucose are used to show vCEST is sensitive to hydroxyl moieties in the presence of MT. Additionally, two subjects with prior ACL injuries are imaged at 3T and vCEST is used to observe detailed features of cartilage that are not present with conventional CEST.

Daniel James Clark^1,2, Alex K Smith^3,4, Michael V Knopp¹, and Seth A Smith^3,4
1Wright Center of Innovation, Department of Radiology, The Ohio State University, Columbus, OH, United States, ²Department of Biomedical Engineering, The Ohio State University, Columbus, OH, United States, ³VUIIS, Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ⁴Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

This study presents theory, simulation, and phantom data for a variable RF pre-saturation power CEST sequence (vCEST) that is promising for hydroxyl detection and simultaneous measurements of amine and NOE signals at 3T. Glycogen and glucose phantoms of varying concentrations were used to show the increased sensitivity to hydroxyl protons. Glycogen and BSA phantoms were used to show that hydroxyl, amide, and NOE signals can be measured simultaneously in a single z-spectrum.

Shu Zhang¹, Jochen Keupp², Zheng Liu³, Robert E. Lenkinski^1,4, and Elena Vinogradov^1,4
1Radiology, UT Southwestern Medical Center, Dallas, TX, United States, ²Philips Research, Hamburg, Germany, ³Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ⁴Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

This abstract studied the dependence of saturation with frequency alternating RF irradiation (SAFARI) on pulsed RF saturation parameters via simulation and phantom experiments. Overall, both APT and SAFARI effects show oscillations and decrease with increasing interpulse delay. The amount of decrease is dependent on RF parameters and the exchange rate. SAFARI is more sensitive to the individual pulse length. Inversion pulses lead to the most efficient saturation. Therefore, efficient saturation can be achieved with increased interpulse delay, thus lowering SAR without compromising CEST effect. The study provides insights for further sequence optimization to be used in various applications.

Sha Sha Yang¹, Ke Jiang¹, and Yin Wu^1
1Paul C. Lauterbur Research Centre for Biomedical Imaging, Shenzhen Key Laboratory for MRI, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China

The omega plot is a facile method to quantify chemical exchange rates. However, its accuracy decreases in measuring protons at small chemical shifts and suboptimal saturation powers may be one of the reasons. In this study, simulations were performed to identify optimal saturation powers by evaluating the consistency between desired omega plot and simulated results. Results showed substantially improved estimation accuracy of exchange rates with saturation powers optimized. The current study confirmed the crucial influence of saturation powers on omega plot performance, and demonstrated the importance of saturation power optimization in improving the estimation accuracy of chemical exchange rates.

Bing Wu¹, Chunmei Li², Min Chen², and Zhenyu Zhou^1
1GE healthcare China, Beijing, Beijing, China, ²Beijing hospital, Beijing, China

CEST acquisition usually consists a series of frequency saturation, which constraint the acquisitions to be single shot for achieving feasible scan time. Hence the resulting images are associated with limited resolution as well as image distortions. However the region of interest (ROI) of CEST study is often spatially limited and known at prescription. In this study, a reduced FOV excitation method is used to exploit this knowledge, and its benefits are demonstrated in a prostate CEST acquisition.

Chien-Yuan Eddy Lin^1,2, Bing Wu², Zhongping Zhang², Zhenyu Zhou², Ai-Chi Chen³, and Chi-Ren Chen^3
1GE Healthcare, Taipei, Taiwan, ²GE Healthcare China, Beijing, China, ³Department of Radiology, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan

Amide proton transfer (APT) is capable of detecting the contrast to the protein level. High-resolution APT may be required for assessing subtle change of pathology. However, it is difficult to acquire APT data with high-resolution due to long scan time required for multiple acquisitions at different frequencies. As a result, a recently developed reduced field-of-view (rFOV) APT sequence was employed to this study and a small brain tumor (size < 0.8 cm³) was used to evaluate the clinical performance of rFOV APT.

Yi Zhang¹, Hye-Young Heo¹, Dong-Hoon Lee¹, and Jinyuan Zhou^1,2
1Division of MR Research, Department of Radiolgoy, Johns Hopkins University, Baltimore, Maryland, United States, ²F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States

Image registration has been widely used as a preprocessing step for ensuring high-quality CEST images, especially for in vivo human applications. The reference image indispensable for registration has been mostly chosen as the unsaturated image in literature. However, there is no report on whether the unsaturated image is the proper choice for the reference image. Here, it’s shown that referencing to the unsaturated image actually degrades the quality of CEST images, and the 3.5 ppm dynamic is the best reference for amide proton transfer imaging.

Julio Cárdenas-Rodríguez¹ and Mark D. Pagel^1
1Biomedical Engineering, University of Arizona, Tucson, AZ, United States

We have designed a new curve fitting method for CEST data using the L1/2 and L1 norms. This methods overcomes the limitations of standard least square curve fitting algorithm, and makes it feasible to obtain robust and quantitative estimates of CEST paramaters in vivo.

James E M Fairney^1,2, Guanshu Liu³, Karin Shmueli¹, and Xavier Golay^2
1Department of Medical Physics & Biomedical Engineering, University College London, London, London, United Kingdom, ²Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, London, United Kingdom, ³F.M.Kirby Center, Kennedy Krieger Institute, Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

Presentation of a method for the comparison of B0 correction methods. This method is based on non-exchanging phantoms to remove CEST effects. SAS method proposed to inform studies.

Shaokuan Zheng¹, Guoxing Lin², Zhongliang Zu³, Yansong Zhao⁴, and Matthew J Gounis^1
1Department of Radiology, UMASS Medical School, Worcester, MA, United States, ²Gustav H. Carlson School of Chemistry, Clark University, Worcester, MA, United States, ³Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ⁴Philips Healthcare, Cleveland, OH, United States

In this study, we performed 1H NMR spectroscopy of red blood cells and subsequently applied Lorentzian fitting of the Z-spectrum, in order to distinguish between the Nuclear Overhauser Effect (NOE) signal and the CEST signal. Two different Lorentzian fitting methods were evaluated for the Z-spectrum acquired at different saturation powers. Three typical saturation powers of 0.54 uT, 2 uT and 4 uT were used to represent low, medium and high power level. We found that Lorentzian fitting method I has a good fitting for Z-spectra acquired at low saturation power and Lorentzian fitting method II has a good fitting for z-spectra acquired at both medium and high saturation power.

Mitsuharu Miyoshi¹, Tsuyoshi Matsuda¹, and Hiroyuki Kabasawa^1
1Global MR Application and Workflow, GE Healthcare Japan, Hino, Tokyo, Japan

MTR asymmetry is often used as a CEST parameter. However, it is influenced by other Z-spectrum peaks or high B1 of preparation RF pulse. In this study, CEST Peak Extraction method was defined and multi peak fitting was tried with a phantom. CEST peak could be fitted with Lorentzian function. B0 inhomogeneity, CEST peak width and peak area were calculated with raw egg white phantom. As a CEST parameter, CEST peak area was better than MTR asymmetry.

Tobias Lenich¹, André Pampel¹, and Harald E. Möller^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Saxony, Germany

We introduce an efficient modeling and simulation method, capable of simulating MR experiments for arbitrary many spin pools. It is based on a matrix-algebra based calculation of the Bloch-McConnell equations for n spin pools, including the effects of cross-relaxation (nuclear Overhauser effect (NOE)), chemical exchange saturation transfer (CEST) and magnetization transfer involving a macromolecular pool (MT) on MR experiments.

Hye-Young Heo¹, Yi Zhang¹, Dong-Hoon Lee¹, Xiaohua Hong¹, and Jinyuan Zhou^1
1Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States

APT imaging has been used to successfully detect malignant gliomas and other cancers. However, the mechanism of APT signal contrast in tumors is still unclear. In this study, we investigated the mixed effects of conventional MT, APT, and NOE using a fitting approach with a multiple-pool proton exchange model, and fitted the APT and NOE signals basing on the prior known, extrapolated semi-solid MTC information. The dependence of APT^# and NOE^# on the RF saturation power was also investigated.

Jae-Seung Lee^1,2, Ding Xia¹, Alexej Jerschow², and Ravinder R. Regatte^1
1Department of Radiology, New York University, New York, NY, United States, ²Department of Chemistry, New York University, New York, NY, United States

In biological tissues and organs, many endogenous CEST agents coexist, and their CEST effects often overlap. Characterizing individual CEST effects from different metabolites would be useful for interpreting such overlapped CEST effects and for designing new CEST applications. Here we performed an in vitro study to evaluate individual CEST effects arising from common metabolites found in biological tissues and organs. The CEST effects of those common metabolites were compared between 3 T and 7 T, in consideration of the exchange regime and the acidity of the exchangeable protons.

Alex Li¹, Miranda Bellyou-Camilleri¹, Joseph Gati¹, Robert Bartha¹, and Ravi Menon^1
1Centre for Functional and Metabolic Mapping, The University of Western Ontario, London, ON, Canada

Based on chemical exchange saturation transfer (CEST), high-resolution glutamate concentration maps were generated in a healthy and tumor mouse using the amide proton transfer (APT) and glutamate CEST (GluCEST) effects at 9.4T.

Olivier E. Mougin¹ and Penny A Gowland^1
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Chemical Exchange Saturation Transfer (CEST) and Chemical Exchange Spin Locking (CESL) have different sensitivities to different exchanging pools. Here we present a simple method to separate overlapping pools such as APT and Glutamate based on a linear combination of signals from different CEST and CESL sequences. The method described here is directly applicable on clinical scanner, and should prove useful in quantification of fast exchanging proton pools

Rong-Wen Tain^1,2, Weiguo Li³, Shaolin Yang⁴, Xiaohong Joe Zhou^1,2, and Kejia Cai^1,2
1Radiology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States, ²Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States, ³Research Resource Center, University of Illinois at Chicago, Illinois, United States, ⁴Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States

The conversion of phosphocreatine (PCr) to creatine (Cr) by the creatine kinase produces ATP. However, 1H-MRS measures the total creatine due to the overlapping of PCr and Cr in 1H-MRS. Other techniques such 31P-MRS is limited by low sensitivity and resolution. The goal of this preliminary study is to prove the concept that PCr and Cr can be individually quantified using a combined proton MR method based on CEST MRI and 1H-MRS. Various PCr and Cr concentration phantoms were scanned using CEST MRI and 1H-MRS. Results demonstrated that PCr and Cr concentration can be individually quantified by using the proposed method.

Olusegun Adegbite¹, Prodromos Parasoglou¹, Lee Jae Seung¹, Ding Xia¹, and Ravinder R. Regatte^1
1Radiology, NYU, Langone Medical Centre, New York, New York, United States

The interconversion between PCr and Cr concentrations under high energy demand is a major activity controlled by creatine kinase (CK) reaction. In this study, we measured the recovery of both PCr and Cr with high temporal resolution through CEST and 31P-MRI, and the preliminary results were presented.

Xiaolei Zhu¹, Shizhen Chen¹, Qing Luo¹, and Xin Zhou^1
1National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Wuhan, Hubei, China

To achieve magnetic resonance imaging (MRI) contrast for temperature changes under the limited tumor microenvironment, a core-shell polymeric micelle which self-assembled with different length of thermo-sensitive chains was designed.

Qi Wang¹, Shizhen Chen¹, Qing Luo¹, and Xin Zhou^1
1National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Wuhan, Hubei, China

A novel reconstituted high-density lipoprotein (rHDL) nanocomposite1 has been prepared for high-sensitive magnetic resonance (MR)-fluorescence multimodal imaging.

Magnetization Transfer & CEST
 

Monday 1 June 2015

Olivier M. Girard¹, Arnaud Le Troter¹, Gopal Varma², Valentin H. Prevost¹, Maxime Guye^1,3, Jean-Philippe Ranjeva^1,3, David C. Alsop², and Guillaume Duhamel^1
1CRMBM UMR 7339, CNRS and Aix-Marseille University, Marseille, France, ²Radiology Department, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States, ³Pôle d'Imagerie Médicale, CEMEREM, APHM, Marseille, France

Inhomogeneous Magnetization Transfer (ihMT) has been proposed as a new technique that provides specific signal from myelinated tissues. 3D ihMT has been previously demonstrated at 3T and highlighted challenges, such as power limitation and non-uniformity of the resulting contrast. This work presents a 3D ihMT prepared GRE sequence implemented at 1.5T, allowing for stronger B₁ and better RF uniformity. Distributions of ihMTR and MTR across the whole brain demonstrated notable differences, and provided great insight for WM characterization. This opens new horizons for future work on WM microstructure and to study diffuse WM pathology such as MS.

Gopal Varma¹, Olivier M Girard², Valentin Prévost², Guillaume Duhamel², and David C Alsop^1
1Radiology, Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States, ²CRMBM UMR 7339, CNRS and Aix-Marseille Université, Marseille, France

Inhomogeneous magnetization transfer (ihMT) shows promise for myelin selective imaging. As with other saturation based techniques, use of the ihMT ratio for quantification is complicated by other contributions, such as T₁ and B₁ inhomogeneity. Examination of the steady-state signal equation with saturation suggests use of the inverse signal and normalization with a high flip-angle (unsaturated) reference can help eliminate these dependencies. Application to ihMT data showed the resultant ihMT-R_ex parameter to be B₁ independent for ihMT saturations of B_1,RMS ≥ 50mG. Maps of ihMT-R_ex provided sharper and more uniform contrast within white matter.

James H Holmes¹, Alexey Samsonov², Pouria Mossahebi³, Diego Hernando², Aaron S Field^2,4, and Kevin M Johnson^5
1Global MR Applications and Workflow, GE Healthcare, Madison, WI, United States, ²Radiology, University of Wisconsin-Madison, Madison, WI, United States,³Department of Medicine, University of Wisconsin-Madison, Madison, WI, United States, ⁴Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, ⁵Medical Physics, University of Wisconsin-Madison, Madison, WI, United States

We demonstrate a method for rapid, motion robust, and quiet quantitative imaging using a time efficient zero echo time acquisition. The method relies on radial sampling to improve motion robustness and reduce scan time using an intermittent MT preparation pulse played every 64 imaging excitations rather than every TR. Quantitative parameters were calculated using a 3 parameter fit model to 2 SPGR imaging flip angle data sets, one MT weighted data set, and a B1 dataset. Results are shown for normal volunteers demonstrating motion robustness and potential for quantitative accuracy.

Marco Battiston¹, James E M Fairney^2,3, Marios C Yiannakas¹, Claudia A M Wheeler-Kingshott¹, and Rebecca S Samson^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, ²Department of Medical Physics and Biomedical Engineering, UCL, London, England, United Kingdom, ³Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, England, United Kingdom

Magnetisation Transfer Ratio (MTR) has previously been measured to detect abnormalities in brain and spinal cord (SC) in a range of pathologies. However, the MTR is influenced by several confounding factors that can reduce its sensitivity to the underlying MT effect and compromise its ability to differentiate tissue types and pathological changes especially in the SC where quantitative measurements are hampered by several technical challenges. Here, we show how MTR sequence parameters can be optimised to improve its sensitivity to macromolecular content of the tissue, providing enhanced contrast between different tissue types. An application in the SC is presented.

Gunther Helms^1,2
1Medical Radiation Physics, Lund University, Lund, Scania, Sweden, ²Cognitive Neurology, Göttingen University Medical Center, Göttingen, Lower Saxony, Germany

Maps of the MT-saturation as derived in FLASH-based multi-parameter mapping (MPM) are largely corrected for effects of flip angle inhomogeneity. Here, we present a heuristic model for residual effects of B1+ that is rooted in the dynamics of macromolecule saturation. Model parameters were validated for brain tissues by variation of the MT-pulse flip angle in an established MPM protocol. White and gray matter exhibited similar values. A post-hoc correction by an independent B1+ map yielded more symmetric MT maps and reduced variation across white matter.

Emily Willson¹ and Heather Whitney^2
1Wheaton College, Wheaton, IL, United States, ²Physics, Wheaton College, Wheaton, IL, United States

We seek to understand how different levels of radiation damping (RD) affect the confidence level of magnetization transfer (MT) parameters extracted from selective inversion recovery measurements. As a part of our long-term project, we begin with single spin system simulation implementing an inversion recovery experiment with increasing degrees of RD to generate NMR spectra. Data is fit to a biexponential decay model and parameters extracted for analysis. This simulation will later be extended to include multiple pool systems.

Zaid Bin Mahbub¹, Olivier Mougin², and Penny Gowland^2
1Arts & Sciences, Ahsanullah University of Science & Technology, Dhaka, Dhaka, Bangladesh, ²SPMMRC, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Imaging the peripheral nerves and their roots can be difficult on MT MRI due to lack of contrast with the surrounding tissues and breathing movements. A new MT DWIBS sequence has been successfully introduced to measure the MTR values for brachial plexus and used for MT, NOE study. Both the nerves and cord showed z-spectra asymmetry. NOE effects could give new insights into the interactions between semisolid tissue and bulk water inside the nerves and cord. In future NOE will be quantified by exploring the z-spectra asymmetry with several offset frequencies and RF powers to study myelination.

Daniel Paech¹, Sina Burth¹, Johannes Windschuh², Jan Eric Meissner², Moritz Zaiss², Oliver Eidel¹, Philipp Kickingereder¹, Peter Bachert², Wolfgang Wick³, Heinz Peter Schlemmer⁴, Ralf Omar Floca⁴, Mark Edward Ladd², Sabine Heiland¹, Martin Bendszus¹, and Alexander Radbruch^1
1Neuroradiology, University Hospital Heidelberg, Heidelberg, Baden-Württemberg, Germany, ²Department of Medical Physics in Radiology, German cancer research center, Baden-Württemberg, Germany, ³Neurooncology, University Hospital Heidelberg, Heidelberg, Baden-Württemberg, Germany, ⁴Department of Radiology, German cancer research center, Baden-Württemberg, Germany

Nuclear Overhauser Enhancement (NOE) mediated CEST at 7 Tesla has recently turned out to provide additional information compared to standard MRI. However, the pathophysiological origin of NOE signal is still under debate. To evaluate possible contributions of cellularity and protein content, fifteen newly diagnosed gliobalstoma patients were enrolled in this study to perform region specific correlation analysis on NOE mediated CEST signal and the apparent diffusion coefficient (ADC). The results indicate that within the area of T2 edema cellularity might contribute to changes in the NOE-signal, whereas changes in the enhancing parts must be due to different origins.

Shaolin Yang^1,2, Minjie Wu¹, Olusola Ajilore¹, and Anand Kumar^1
1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, ²Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States

Reduced functional connectivity within the brain’s default mode network (DMN) and impaired connecting white matter tracts have been reported in type 2 diabetes mellitus (T2DM). However, it is unknown whether the DMN nodal regions themselves are also compromised. In this study, magnetization transfer (MT) imaging was applied on twenty T2DM patients and twenty-six healthy controls. Compared with controls, T2DM patients had significantly lower MT ratio (MTR) in posterior cingulate cortex (PCC), while no significant differences in other DMN regions. Reduced PCC MTR correlated with T2DM-related clinical measures. The impaired PCC in DMN may provide insights into neurological pathophysiology of T2DM.

James H Holmes¹, Kevin M Johnson², Diego Hernando³, Scott B Reeder^2,3, and Alexey Samsonov^3
1Global MR Applications and Workflow, GE Healthcare, Madison, WI, United States, ²Medical Physics, University of Wisconsin-Madison, Madison, WI, United States,³Radiology, University of Wisconsin-Madison, Madison, WI, United States

Magnetization transfer (MT) imaging is challenging in the presence of fatty tissues due to the absence of an MT effect in fat as well as the interference between fat and MT-attenuated water signal due to chemical shift. We demonstrate a method that improves MT imaging in the presence of fat by combining MT with a multi-echo chemical shift encoded technique. Results in phantoms demonstrate more robust MT ratios despite the presence of fat. In vivo results show improved stability of MTR measurements in fat containing tissues including fatty liver disease.

Hye-Young Heo¹, Shruti Agarwal², Craig Jones^1,3, Jun Hua^1,3, Nirbhay Yadav^1,3, Jinyuan Zhou^1,3, Peter C.M van Zijl^1,3, and Jay J. Pillai^2
1Division of MR Research, Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States,²Division of Neuroradiology, Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States,³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States

APT-weighted MRI has shown the potential to detect gliomas, to differentiate glioma cores from peritumoral edema, and to separate recurrent tumor from treatment necrosis. When acquiring Z-spectra using low RF power pulsed steady-state CEST acquisition with the purpose of reducing semi-solid MT contrast (MTC) and reducing and narrowing direct saturation effects, saturation-transfer effects based on slow exchange are pronounced, such as upfield relayed NOE signals and downfield CEST/APT signals. In this study, we assessed the ability of APT/NOE imaging to differentiate histologic grades of de novo primary gliomas at 7T.

Vitaliy Khlebnikov¹, Jeroen Siero¹, Jannie Wijnen¹, Fredy Visser², Peter Luijten¹, Dennis Klomp¹, and Hans Hoogduin^1
1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ²Philips Healthcare, Best, Netherlands

Chemical Exchange Saturation Transfer (CEST) has attracted a lot of attention due to its sensitivity to cellular protein content and pH. However, those useful properties, mainly APT (Amide Proton Transfer) and NOE (nuclear overhauser enhancement) are often contaminated with a magnitude of confounding effects, which in turn can lead to error-prone conclusions. The aim of this work is to compare pure effects of APT and NOE in white and gray matter in healthy human brain at 7T.

Ke Li^1,2, Hua Li^1,3, Xiao-Yong Zhang^1,2, Ashley M Stokes^1,2, Hakmook Kang⁴, Zhongliang Zu^1,2, Chad C Quarles^1,2, Daniel F Gochberg^1,2, John C Gore^1,2, and Junzhong Xu^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 Physics and Astronomy, Vanderbilt University, Nashville, TN, United States, ⁴Department of Biostatistics, Vanderbilt University, Nashville, TN, United States

Quantitative Magnetization Transfer provides measurements of macromolecular content in biological tissues based on a two-pool model. This might be oversimplified for biological tissues, such as tumor, which consists of multiple water compartments. This work demonstrated that with the presence of intermediate to fast water exchange, the two-pool model is sufficient to describe qMT data in tumors. Numerical simulations validated this hypothesis. Further validations were performed by injecting Gd-DTPA to selectively alter extracellular relaxation properties in tumor bearing animals. Across all dynamics, there were no significant changes in the obtained pool size ratios.

Rong-Wen Tain^1,2, Weiguo Li³, Tibor Valyi-Nagy⁴, Xiaohong Joe Zhou^1,2, and Kejia Cai^1,2
1Radiology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States, ²Center for MR Research, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States, ³Research Resource Center, University of Illinois at Chicago, Illinois, United States, ⁴Pathology, College of Medicine, University of Illinois at Chicago, Illinois, United States

Magnetization transfer (MT) can occur via chemical exchange saturation transfer (CEST) and/or dipole-dipole interactions (Nuclear Overhauser Enhancement or NOE). This study aims to investigate the sensitivity of MT in the broad definition to oxidative stress through controlled ex vivo studies. Z-spectra were acquired from egg white and lamb brain tissues treated with hydrogen peroxide for one hour. In the Z-spectra, distinctive reductions in the NOE, CEST and the semi-solid MT contrasts were seen due to induced oxidative stress. We demonstrated the sensitivity of magnetization transfer is dependent on the level of induced oxidative stress.

Alex K. Smith^1,2, Lindsey M. Dethrage^2,3, Samantha By^1,2, Siddharama Pawate⁴, and Seth A. Smith^2,3
1Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ²Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ³Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ⁴Neurology and Neuroimmunology, Vanderbilt University, Nashville, TN, United States

Visual dysfunction is a hallmark of MS and may arise from damage to components of the visual system, such as the optic nerve (ON). Understanding the changes that accompany this damage may offer a biomarker for MS. We implemented an APT-CEST protocol to characterize amide content in healthy ON tissue. Nine controls were imaged at 3T and the data fit to a model of the direct-water-saturation curve. The mean %AUC values in each ON were found to be 1.74±1%(L) and 1.63±1%(R). These findings suggest CEST can be accurately quantified in healthy ON and may provide a biomarker for MS prognosis.

Eleni Demetriou¹, Andreia C Silva¹, Marilena Rega¹, Francisco Torrealdea¹, James E M Fairney^1,2, Mohamed Tachrount¹, Mark Farrow³, and Xavier Golay^1
1Brain repair and rehabilitation, Institute of Neurology, London, United Kingdom, ²Medical Physics &Biomedical engineering, University College of London, London, United Kingdom, ³MRC prion unit, UCL Institute of Neurology, London, United Kingdom

In this study, we apply Chemical Exchange Saturation Transfer (CEST) to examine changes related to protein folding and aggregation occurring in a terminal mouse model of prion disease. A trend towards increased amide proton transfer in the Prion mice was found in the cortex and basal ganglia but was not statistically significant .However, this was also accompanied by a significant reduction found in the magnetization transfer asymmetry at 10μT power in both basal ganglia and cortex of the diseased animals, suggestive of changes happening in the local proteasome possibly indicating cell death at this late stage of this disease, in addition to a reduced number of exposed amine groups due to PrP misfolding.

Adrienne Dula¹, Siddharama Pawate¹, Lindsey M Dethrage¹, Benjamin N Conrad¹, and Seth A Smith^1
1Vanderbilt University, Nashville, Tennessee, United States

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Feng Wang^1,2, Zhongliang Zu^1,2, Tung-Lin Wu², John C. Gore^1,2, and Li Min Chen^1,2
1Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ²Institute of Imaging Sciences, Vanderbilt University, Nashville, TN, United States

Non-human primates provide valuable pre-clinical models for studying spinal cord injuries (SCI). The metabolites and byproducts from injuries could exhibit CEST (Chemical Exchange Saturation Transfer) effects due to their exchangeable protons on hydroxyl, amine and amide residues. Here we recorded and interpreted the z-spectra of abnormalities formed after SCI at 9.4T. Different CEST mapping schemes were compared to evaluate regional changes around the sites of lesions. Characteristic features extracted from z-spectra enable the non-invasive spatial and longitudinal assessments of spontaneous recovery from SCI.

Frithjof Wickrath¹, Anja Müller-Lutz¹, Christoph Schleich¹, Benjamin Schmitt², Tom Cronenberg¹, Rotem Shlomo Lanzman¹, Falk Miese¹, and Hans-Jörg Wittsack^1
1Department of Diagnostic and Interventional Radiology, University Dusseldorf, Medical Faculty, D-40225 Dusseldorf, NRW, Germany, ²Healthcare Sector, Siemens Ltd. Australia, Australia

The aim of this study was to evaluate, if the chemical exchange saturation transfer effect of glycosaminoglycans (gagCEST) representing the amount of glycosaminoglycans alters with age in the cartilage of human lumbar intervertebral discs. Therefore gagCEST imaging was applied on a 3T MR scanner. The gagCEST effect measured using the asymmetric magnetization transfer ratio decreases with age. These results strengthen the idea of a loss of glycosaminoglycan content with age. Hence, age-matched gagCEST analysis is necessary in future.

Elena Vinogradov^1,2, Zheng Liu³, Ananth Madhuranthakam^1,2, Asghar Hajibeigi¹, Adrien Jump⁴, Ivan Pedrosa^1,2, Orson W Moe⁴, and Robert E Lenkinski^1,2
1Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ³Advanced Imaging Research Center,Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon, United States, ⁴Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Kidney ailments affect millions of people. Many of these diseases alter normal pH and urea distribution in tissue, prior to apparent morphological changes in the kidney or biochemical changes in blood and urine. Imaging is a powerful tool to assess regional alternations. Here we investigate the application of CEST to monitor kidney function using endogenous urea (urCEST). We present images from healthy volunteers acquired at 3T as well as urCEST modulation following a simple intervention. UrCEST may become a powerful asset in the non-invasive evaluation of kidney function and disease. Moreover, application of quantification methods may lead to pH and urea concentration maps in-vivo.

Shuzhong Chen¹, Min Deng¹, Jing Yuan², and Yi-Xiang Wang^1
1Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, ²Medical Physics and Research Department, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong

CEST MR is a promising molecular imaging technique which enables indirect detection of metabolites with exchangeable protons or molecules. Both APT and glycoCEST value decrease after CCl4 48 hours injection and 24 hours fasting. However, compared with APT, glycoCEST shows high intra- and inter-subject standard deviation in both experiments. This may due to the rapid exchange rate of glycogen hydroxyl protons and their proximity to the water resonance. The observed change in APT reflected the alteration of amide proton levels by injecting CCl4 and fasting. The reliability of glycoCEST in vivo liver at 3T should be further investigated.

Vitaliy Khlebnikov¹, Daniel Polders², Dennis Klomp¹, Jeroen Hendrikse¹, Piere Robe³, Eduard Voormolen³, Peter Luijten¹, and Hans Hoogduin^1
1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ²Philips Healthcare, Best, Netherlands, ³Brain Division, University Medical Center Utrecht, Utrecht, Netherlands

Any difference in micro-environment between normal tissue and tumour can potentially be exploited in therapy. Amide Proton Transfer (APT) imaging is a potentially powerful tool in bringing to light these differences due to its sensitivity to pH and protein content at high spatial resolution. Also, it is important to compare pure effects (without contamination from confounding effects, e.g. water T1 effect) to cast light on pathology. The purpose of this pilot study was to compare true APT with traditional asymmetry (MTRasym) in a variance of brain tumour patients at 7T to investigate the value of APT imaging in tumours.

Ryan Nicholas Schurr¹, Huyen T. Nguyen², Kamal Pohar³, Amir Mortazavi⁴, Zarine Shah², Debra Zynger⁵, Michael V. Knopp², and Guang Jia^1
1Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana, United States, ²Department of Radiology, The Ohio State University, Ohio, United States, ³Department of Urology, The Ohio State University, Ohio, United States, ⁴Department of Internal Medicine, The Ohio State University, Ohio, United States, ⁵Department of Pathology, The Ohio State University, Ohio, United States

Z-spectra from healthy and malignant regions of bladder cancer patients of bladder cancer patients are fit as separate components upfield and downfield from water, and the magnitude of the MTR asymmetry is calculated at 2.0 ppm and 3.5 ppm offset frequencies using the results of the fitting process. The MTR asymmetry at the 3.5 ppm offset frequency is statistically significantly different between tumor and normal bladder wall, suggesting that this technique is able to distinguish between the two regions.

Vitaliy Khlebnikov¹, Alex Bhogal¹, Jeroen Siero¹, Michel Italiaander², Vincent Boer¹, Peter Luijten¹, Hans Hoogduin¹, and Dennis Klomp^1
1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ²MR Coils BV, Drunen, Netherlands

pH homeostasis is vital to normal cellular physiology. 31P Magnetic Resonance Spectroscopy (31P MRS) is currently a gold standard for the non-invasive measurements of intracellular pH (pHi) using inorganic phosphate (Pi) as a probe. Low resolution and low pH sensitivity are major limitation of 31P-based pH measurements. The aim of this work is to show that emerging APT (Amide Proton Transfer) imaging is superior to 31P MRS in terms of both resolution and pH sensitivity by getting an estimate on buffering capacity of different brain compartments in healthy human brain at 7T.