Joint Annual Meeting ISMRM-ESMRMB 2014 10-16 May 2014 Milan, Italy

3291-3314 CEST Contrast: Methods & Applications
3315-3338 CEST, NOE & MT

CEST Contrast: Methods & Applications
Monday 12 May 2014
Exhibition Hall  10:45 - 11:45

  Computer #  
49 Measuring the z-spectrum at various saturation powers simultaneously: development of a Look Locker- MT sequence
Olivier E Mougin1 and Penny A Gowland1
1SPMMRC, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

A new magnetization transfer sequence based on a Look and Locker scheme is presented here. The optimization of the saturation as well as the imaging parameters was performed to get the highest CNR possible, focusing on the possibility to measure NOE and MT thanks to the different saturations available in the LL images, and this in a minimum amount of time.

3292.   50 Accelerated CEST-MRI of in vivo human brain using Compressed Sensing at 3T: a pilot study
Qinwei Zhang1, Yanjie Zhu2, Jing Yuan1,3, Shuzhong Chen1, Deyond Siu1, Min Deng1, Yi-Xiang J Wang1, and Dong Liang2
1Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, 2Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Shenzhen, Guangdong, China, 3CUHK Shenzhen Research Institute, Shenzhen, Guangdong, China

CEST-MRI is a promising molecular imaging technique while suffers from long scan time and low contrast-to-noise ratio (CNR) in clinical use. In this study, we proposed the use of compressed sensing (CS) to accelerate the CEST-MRI at 3T. Full-sampled CEST-MRI data of in vivo human brain were retrospectively under-sampled and reconstructed up to a reduction factor of four. The CS-reconstructed magnetization transfer ratio asymmetry and ΔB0 maps showed excellent consistency with those using normal reconstruction from full samples. Goodness-of-fit of the CS-reconstructed Z-spectrum fitting was even better than the fully sampled one.

3293.   51 Prospective motion correction with EPI volume navigators for chemical exchange saturation transfer (CEST) imaging
Robert Frost1, Aaron T. Hess2, Nicholas P. Blockley1, Yee Kai Tee3, Michael A. Chappell1,3, M. Dylan Tisdall4,5, Andre J. W. van der Kouwe4,5, and Peter Jezzard1
1FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, 2Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom, 3Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom, 4A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, 5Radiology, Harvard Medical School, Boston, MA, United States

Chemical exchange saturation transfer (CEST) is a promising technique for treatment planning in acute stroke. However, when using single-slice measurements, the CEST acquisition is particularly susceptible to through-plane patient motion, which cannot be corrected in post-processing with 2D image registration. Here we used prospective motion correction with 3D EPI volume navigators to update the position of the imaging slice in real time, with no increase in scan duration and minimal effect on the image contrast. Maps of magnetization transfer asymmetry were compared in cases of no motion and deliberate motion to demonstrate the improvement in data quality with prospective motion correction.

3294.   52 Using Simultaneous Multi-Slice Excitation to Accelerate CEST Imaging
Dapeng Liu1,2, Rong Xue1,2, Jinyuan Zhou3,4, Jing An5, Xinyuan Miao1, and Danny JJ Wang2,6
1State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, 2UCLA-Beijing Joint Center for Advanced Brain Imaging, Beijing, China and Los Angeles, California, United States, 3Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 4F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 5Siemens Shenzhen Magnetic Resonance Ltd, Shenzhen, China, 6Department of Neurology, University of California Los Angeles, Los Angeles, United States

Chemical exchange saturation transfer (CEST) imaging is a novel MRI technique that can detect low-concentration solutes in tissue compared to routine water MR images. However, a long scan time due to multiple repetitions required to acquire a full frequency spectrum or to increase signal-to-noise ratios and a long saturation pulse (or pulse train) have restricted its practical clinical application that typically needs multi-slice measurements. Here we present an efficient and accelerated CEST imaging technique using a simultaneous multi-slice (SMS) excitation Turbo-FLASH (TFL) sequence in human brain at 3 T.

3295.   53 Ultrafast chemical exchange saturation transfer imaging based on spatiotemporal encoding
Miao Zhang1, Jianhua Lu1, Lin Chen1, Shuhui Cai1, Congbo Cai1, and Zhong Chen1
1Department of Electronic Science, Xiamen University, Xiamen, Fujian, China

CEST MRI can detect low-concentration compounds with exchangeable protons through saturation transfer to water. This technique is generally time-consuming, as it requires acquisition of saturation images at multiple frequencies. EPI is the most common ¡°ultrafast¡± MRI approach, but it suffers from artifacts of susceptibility heterogeneities and chemical shift effect. The spatiotemporally encoded (SPEN) method possesses higher built-in immunity to heterogeneity while retaining the temporal and spatial performance of EPI. In this abstract, SPEN is applied to improve the acquisition efficiency and image quality of CEST. The feasibility of CEST SPEN is demonstrated by experiments on creatine solution phantoms.

3296.   54 Rapid PROPELLER-CEST Encoding with Background Asymmetry Subtraction for Ultrafast Z-Spectrum Acquisition
Hoonjae Lee1, Chul-Ho Sohn2, and Jaeseok Park1
1Department of Brain and Cognitive Engineering, Korea University, Seoul, Korea, 2Department of Radiology, Seoul National University Hospital, Seoul, Korea

In this work we propose a novel, rapid propeller-CEST encoding with background asymmetry subtraction for ultrafast z-spectrum acquisition, wherein 1) off-resonant saturation and corresponding CEST encoding are performed along the angular (blade) direction over the entire k-space, 2) motion- and field-corrected z-spectrum data is synthesized using only a single k-space data (synthesize low frequency CEST signals while sharing high frequency signals), and 3) propeller-CEST encoding induced background asymmetry is subtracted from the z-spectrum. It is expected that the proposed method becomes a highly efficient alternative to conventional CEST for rapid z-spectrum acquisition and accurate CEST asymmetry analysis.

3297.   55 Preliminary evaluation of compress sensing chemical exchange saturation transfer (CEST) MRI
Gang Xiao1, Phillip Zhe Sun2, Zhuozhi Dai3, and Renhua Wu3
1Department of Mathematics and Statistics, Hanshan Normal University, Chaozhou, Guangdong, China, 2Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown£¬ MA, United States, 3Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Guangdong, China

A feasible way to accelerate data acquisition while maintaining accurate CEST characterization is highly desirable. We here postulated that compressed sensing (CS) can be applied to reduce the acquired data by a factor up to 5 without losing CEST quantification accuracy. CS technique was verified with experimental measurements from a tissue-like phantom, and the results showed that CESTR with undersampling rate R < 5 agree reasonably well with those of fully sampled data. In summary, our study demonstrates the feasibility of CS technique to accurate quantify CEST MRI.

3298.   56 Simulating variable RF power pre-saturation schemes to enhance CEST contrast for exchangeable protons near 1.0 ppm
Daniel James Clark1,2, Seth A Smith3,4, and Michael V Knopp1
1Wright Center of Innovation, Department of Radiology, The Ohio State University, Columbus, OH, United States, 2Departmemt of Biomedical Engineering, The Ohio State University, Columbus, OH, United States, 3Vanderbilt University Institute of Imaging Science,Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 4Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

In CEST MRI sensitivity to hydroxyl protons is difficult because of small chemical shifts and fast exchange rates, most evident on clinical scanners where the spectral separation is less and the signal is confounded by magnetization transfer and direct water saturation. We propose a novel, variable RF power pre-saturation scheme and present simulations which show that such a scheme can flatten the direct water saturation component of the z-spectrum curve, enhancing CEST contrast from hydroxyl moieties (1 ppm). We further examine the impact of the variable saturation scheme in the presence of concomitant MT and DWS effects.

3299.   57 CEST imaging with phase cycled rectangular RF preparation pulse: analytical solution, simulation and phantom study
Mitsuharu Miyoshi1, Tsuyoshi Matsuda1, and Hiroyuki Kabasawa1
1Global MR Applications and Workflow, GE Healthcare Japan, Hino, Tokyo, Japan

Chemical Exchange Saturation Transfer (CEST/APT) is a new contrast for clinical MRI. Because of SAR and RF amplifier limitation, continuous RF is not available in human clinical scanner. Although pulsed RF was used, the meaning of Z-spectrum is not clear. In this study, novel CEST preparation pulse with phase cycled 0.232ms rectangular shaped RF pulse was developed. Z-spectrum matched well between analytical solution and simulation. Z-spectrum of phantom was measured with 3T clinical scanner. B1/SAR was 4.5(ET)/1.0 (W/kg) and less. Simulation and phantom study show that phase cycled RF pulse can be used for CEST imaging.

3300.   58 Selection of irradiation parameters to minimize asymmetric magnetization transfer and NOE contributions in CEST
Tao Jin1 and Seong-Gi Kim1,2
1Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2Center for Neuroscience Imaging Research, Department of Biological Sciences, SKKU, Suwon, Korea

Magnetization transfer ratio asymmetry (MTRasym) analysis of CEST studies removes direct water saturation and other symmetric non-CEST contributions. However, in vivo MTRasym is still confounded by asymmetric contributions, including magnetization transfer contrast from immobile macromolecules (MTCIM) such as myelin, and nuclear Overhausser effects (NOE). Compared with the long-duration, low-power saturation of conventional CEST, it was recently reported that irradiation of shorter duration and higher power enhances sensitivity to amine and hydroxyl protons. In this work we report that higher irradiation power at shorter duration also provides another important advantage by minimizing contributions from MTCIMand NOE.

3301.   59 Optimal Control in Fast Exchange ParaCEST
Giaime Rancan1,2, Thi Thoa Nguyen1, Silvio Aime2,3, Markus Schwaiger4, and Steffen Glaser1
1Technische Universität München, München, Germany, 2Institute for Advanced Study, Garching, Germany, 3Universitá degli Studi di Torino, Torino, Italy, 4Klinikum rechts der Isar, München, Germany

Optimal control algorithms can provide the perfect framework for a facile and flexible tailoring of pulses to experimental conditions in well characterized two or three pool exchange systems. A CEST contrast agent of clinical interest, YbHPDO3A, is considered for presaturation pulse optimization, revealing the non-optimality of standard continuous wave irradiation under the considered energy limitations.

3302.   60 Steady-state pulsed Chemical Exchange Saturation Transfer Imaging of creatine in human calf muscle followed by spillover correction evaluation
Eugenia Rerich1, Moritz Zaiss1, and Peter Bachert1
1Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany

In skeletal muscle endogenous chemical exchange saturation transfer (CEST) effects are influenced by direct water saturation and magnetization transfer (MT) effects. In this study we present a method which corrects the CEST data from spillover and apply it to in vivo data of human calf muscle. The results are compared with the more common evaluation method - the asymmetry analysis of the Z-spectrum.

3303.   61 B1-correction of isolated, spillover-corrected CEST-effects at 7 T
Johannes Windschuh1, Moritz Zaiss1, Jan-Eric Meissner1, and Peter Bachert1
1Medical Physics in Radiology, German Cancer Research Center (DFKZ), Heidelberg, Baden-Württemberg, Germany

The in vivo images of isolated CEST-effects aquired in whole–body scanners at ultra-high fields usually suffer from a strong spatial dependence. This is due to the influence of the rf amplitude (B1) on the effects and B1 inhomogeneities in the large FOV. It is shown that the acquisition of three CEST-images at different B1-amplitudes yield homogeneous APT and NOE maps when using the inverse metric MTRRex for spillover correction.

3304.   62 Spillover, MT and R1 corrected chemical exchange saturation transfer (CEST) imaging in ischemic stroke
Hua Li1, Zhongliang Zu1, Moritz Zaiss2, Imad S. Khan3, Robert Singer3, Daniel F. Gochberg1, Peter Bachert2, John C. Gore1, and Junzhong Xu1
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, 2Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, BW, Germany, 3Section of Neurosurgery, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States

CEST provides the ability to detect small solute pools through indirect measurement of the attenuated water signals. However, conventional quantification methods are affected by various confounding factors like MT, asymmetric MT effects, water longitudinal relaxation, and RF spillover. In the current study, the three-offset method and the 1/Z method were combined to correct the above influences and hence provide a more specific exchange rate weighted contrast in a rat model of ischemic stroke. The results demonstrate the applicability of the inverse Z-spectrum analysis for in vivo applications. The corrected APT shows more significant ischemic contrast. This study may provide insights into improved APT imaging.

3305.   63 Usefulness of Three-Pool Lorentzian Model in Estimating APT effect and Parameterizing Spectral Curve Shape
1Center for MR Research, Korea Basic Science Institute, Cheongwon-Gun, Chungbuk, Korea, 2Institute of Imaging Science, Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 3Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea

This preliminary study presents the results from human brain tumor research using APT MR imaging. In this study, we found that three-pool Lorentzian curve fit to the original z-spectrum can provide not only the measure of CEST effect, but also a useful parametric map in delineating brain tumor lesions. In comparison to Gd-enhanced T1w image, parameterized spectral curve shape, similarly to non-enhanced T1w, provided decreased lesion intensity, while APT effect presented increased signal in the region of glioblastoma.

3306.   64 Simplified simultaneous determination of CEST agent concentration and exchange rate - permission withheld
Phillip Zhe Sun1, Gang Xiao2, and Renhua Wu3
1Radiology, Martinos Center for Biomedical Imaging, Charlestown, MA, United States, 2Department of Math and Applied Mathematics, Hanshan Normal University, Guangdong, China, 3Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Guangdong, China

Simplified quantitative CEST (qCEST) analysis capable of characterizing the underlying CEST system provides tremendous advantage over the conventional CEST-weighted MTR asymmetry analysis. We here postulated that both labile proton ratio and exchange rate can be simultaneously determined using omega plot analysis of a cross-term normalized CEST ratio. The proposed qCEST analysis was validated experimentally in a phantom with concurrent concentration and pH variation. In summary, our study established a simplified qCEST analysis algorithm, which remains promising to aid the ongoing development of qCEST MRI.

3307.   65 Assessing Different Amide Proton Transfer (APT) Quantification Methods in Hyper-acute Stroke Patients
Yee Kai Tee1, George Harston2, Nicholas Blockley3, Thomas Okell3, Jacob Levman1, Martino Cellerini4, Fintan Sheerin4, Peter Jezzard3, James Kennedy2, Stephen Payne1, and Michael Chappell1
1Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxfordshire, United Kingdom, 3FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxfordshire, United Kingdom, 4Department of Neuroradiology, Oxford University Hospitals NHS Trust, Oxfordshire, United Kingdom

Amide proton transfer (APT) imaging is an emerging pH mapping MRI technique that has potential to identify salvageable tissue prior to irreversible infarction after stroke. However, the most widely used APT quantification method suffers from many confounding factors. In this study, 3 different APT quantification methods were studied on data acquired from healthy subjects and hyper-acute stroke patients (<6 hours of onset). It was found that a model-based approach, where the modified Bloch equations were fitted to measured data, was able to quantify the APT effect better than the widely used metric on both the healthy and patient data.

3308.   66 Isolation of CEST contrasts from asymmetric MT effects in a human brain
Jae-Seung Lee1,2, Ding Xia1, Yulin Ge1, Alexej Jershow2, and Ravinder Regatte1
1Radiology, New York University, New York, NY, United States, 2Chemistry, New York University, New York, NY, United States

Chemical exchange saturation transfer (CEST) has great potential to enhance the detection of exchangeable proton species such as low concentrations of metabolites in vivo brain. However, CEST effects are often masked by asymmetric magnetization transfer (MT) effects from macromolecules in tissues and organs. Here, we show that the asymmetry of MT effects in the brain is large enough to overshadow the CEST effects and that the so-called uniform-MT (uMT) method may be useful to reveal the genuine CEST contrast.

3309.   67 Amide Proton Transfer (APT) Imaging of Stroke with Corrections for Relaxation and MT effects
Zhongliang Zu1, Hua Li1, Junzhong Xu1, Daniel F Gochberg1, and John C Gore1
1Vanderbilt University, Nashville, TN, United States

Conventional measurements of APT contrast are confounded by several factors including water relaxation, the influence of solid components, and nearby amines, and so are not specific for detecting changes in concentration or exchange rate of amides. These confounding factors vary during ischemia influence pH measurements. In this study, a novel method named CERTex is described which corrects for such factors and produces images that are more specifically ksw (and thus pH) dependent. Simulations and experiments show that CERTex has better specificity and sensitivity than conventional APT imaging methods for delineating effects of stroke at 9.4 T.

3310.   68 Molecular Imaging of Fibrotic Remodeling and Functional Microcirculation using a novel MT/CEST Encoded Steady State Cardiac Cine MRI Pulse Sequence.
Moriel Vandsburger1, Katrien Vandoorne2, Roni Oren2, Avigdor Leftin2, and Michal Neeman2
1Physiology and Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States, 2Weizmann Institute of Science, Rehovot, Israel

Molecular imaging of the heart is critical for detection of early signs of disease and for monitoring response to therapy. We present the development of a steady state retrospectively gated cardiac cine imaging sequence in which the presence of fibrosis or CEST contrast agents was encoded into the myocardial signal intensity. We applied this technique for quantification of fibrotic scar formation in the mouse heart after myocardial infarction, and for imaging of the myocardial microcirculation following intravenous injection of a CEST contrast agent. Since contrast from each target is selectively encoded, this technique can potentially enable multiplexed imaging of multiple molecular targets at high-resolution in the heart.

3311.   69 A Repeatability Study of Amide Proton Transfer Imaging in the Head and Neck at 3T
Shuzhong Chen1, Wang Lam1, Ann D King1, Kunwar S Bhatia1, Benjamin King Hong Law1, Qinwei Zhang1, David Ka Wai Yeung1, Yi-Xiang J Wang1, Jinyuan Zhou2, and Jing Yuan1,3
1Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, 2Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, 3CUHK Shenzhen Research Institute, Shenzhen, Guangdong, China

Our pilot study has showed that APT-MRI is feasible for the use in the head and neck (HN) and has potentials for HN cancer characterization at 3T. However, HN-APT-MRI is technically challenging due to tissue heterogeneity, pronounced susceptibility and various motions, which may potentially compromise the APT quantification in different scans. To this end, we investigated the repeatability of HN-APT-MRI on healthy volunteers and successfully demonstrated that consistent inter-scan APT contrast could be achieved in major HN tissues. This study is helpful to establish the HN-APT-MRI repeatability so as to ensure its reliability for future clinical use.

3312.   70 Scan-rescan reproducibility of parallel transmission based amide proton transfer imaging of brain tumors
Osamu Togao1, Takashi Yoshiura1, Jochen Keupp2, Akio Hiwatashi1, Koji Yamashita1, Kazufumi Kikuchi1, Yuriko Suzuki3, Koji Sagiyama4, Masaya Takahashi4, and Hiroshi Honda1
1Clinical Radiology, Graduate School of Medical Science, Kyushu University, Fukuoka, Fukuoka, Japan, 2Philips Research Europe, Hamburg, Germany,3Philips Electronics Japan, Tokyo, Japan, 4Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States

APT imaging is a specific type of endogenous CEST imaging technique. APT imaging can be useful in grading gliomas, diagnosing radiation necrosis, and evaluation of therapeutic effect. Observed signal changes in APT imaging is small and it can be influenced by the accuracy of saturation pulse and B0 inhomogeneity correction. We have developed a parallel RF transmission based technique, which allows arbitrarily long saturation pulses via amplifier alternation in clinical scanners. This method is combined with a special RF shimming for B1 homogeneity. In this study we assessed the reproducibility of this method in brain tumors by a scan-rescan test.

3313.   71 Chemical Exchange Saturation Transfer MR Imaging of Parkinson's Disease at 3 Tesla - permission withheld
Chunmei Li1, Shuai Peng1, Rui Wang1, Haibo Chen1, Wen Su1, Xuna Zhao2, Jinyuan Zhou3, and Min Chen1
1Beijing Hospital, Beijing, Beijing, China, 2Peking University, Beijing, China, 3Johns Hopkins University, Maryland, United States

Chemical Exchange Saturation Transfer MR Imaging of Parkinson¡¯s Disease at 3 Tesla This present study was the first to evaluate PD patients with CEST imaging. Our results clearly show that the non-invasive CEST MRI methodology generated unique image contrasts that are based on the changes in cytoplasmic proteins and peptides, as well as the neuronal loss in several specific brain regions in PD patients. The CEST MRI signals show great potential as imaging biomarkers that could detect disease and predict the progression.

3314.   72 Chemical Exchange Saturation Transfer (CEST) Imaging of the Molecular Progression of Neuronal Loss in a Parkinson's Disease Rat Model- permission withheld
Julius Juhyun Chung1,2, Sunyoung Chae1,2, Moon-sun Jang3, Jae-hun Kim4, Geun Ho Im3, Seong-Gi Kim2,5, and Jung Hee Lee1,4
1Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea, 2Center for Neuroscience Imaging Research, Institute for Basic Sciences, Sungkyunkwan University, Suwon, Korea, 3Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Seoul, Korea, 4Department of Radiology, Samsung Medical Center, Seoul, Korea, 5Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

: Despite the growing prevalence of Parkinson’s disease, the progression of neuronal loss in the dopaminergic nigrostriatal pathway has yet to be fully elucidated. In this study, we utilize chemical exchange saturation transfer (CEST) to examine molecular changes in progressive neuronal loss in a 6-hydroxydopamine induced rat model. In particular, we examined Amide Proton Transfer (APT*) and the Nuclear Overhauser Effect (NOE*) as indicators of macromolecular protein changes and investigated the additional information that may be ascertained from Amine Proton EXchange (APEX).



Monday 12 May 2014
Exhibition Hall  11:45 - 12:45

  Computer #  
3315.   49 Quantification of the Contributions to Amide Proton Transfer (APT) Contrast
Zhongliang Zu1, Hua Li1, Junzhong Xu1, Daniel F Gochberg1, and John C Gore1
1Vanderbilt University, Nashville, TN, United States

Amide proton transfer (APT) imaging has been increasingly applied to several pathologies, and new variants of APT imaging have been also proposed. However, APT contrast in practice depends on multiple experimental and sample parameters, especially for in vivo applications. Its specificity to amide-water exchange effects is not clear in many cases. Here, we systematically studied contributions to APT contrast separately through simulations and provide criteria for CEST researchers to evaluate the specificity of new APT imaging methods and guide interpretation of contrast sources.

3316.   50 Interpretation of conventional APT contrast in tumor and ischemic tissue
Zhongliang Zu1, Hua Li1, Junzhong Xu1, Daniel F Gochberg1, and John C Gore1
1Vanderbilt University, Nashville, TN, United States

APT provides a potential method for detecting changes in mobile proteins/peptides or pH, and has been applied to several pathologies including tumor and stroke. However, the in vivo contrast seen is complex and not fully understood. Here, we interpret the conventional APT contrast in tumor and postmortem tissues via experiments and simulations. We found that conventional APT contrast from asymmetry analyses of both tumor and ischemia CEST data at lower fields (e.g. 4.7T) is derived mostly from amine especially at high irradiation power, whereas contrast from tumors at high field (e.g. 9.4T) comes mostly from the MT asymmetry and NOEs.

3317.   51 pH-sensitive MR imaging without dependence on labile proton concentration
Tao Jin1 and Seong-Gi Kim1,2
1Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2Center for Neuroscience Imaging Research, Department of Biological Sciences, SKKU, Suwon, Korea

The pH is an important index of celluar function. Chemical exchange-sensitive MRI techniques that provide pH-weighted imaging have already been applied to stroke and evaluation of cell viability in celluar therapies. However, chemical exchange signals are dependent on both labile proton concentration and exchange rate (i.e., pH), so in the many preclinical and clinical applications where labile proton concentrations significantly change, these pH-weighted signals are considerably contaminated. Correct interpretation of signal changes therefore requires an imaging method highly-sensitive to generation of pure pH contrast, with no dependence on labile proton concentration, as is proposed in this study.

3318.   52 A comparison of iopromide and iopamidol, two acidoCEST MRI contrast agents that measure tumor extracellular pH
Brianna F. Moon1, Liu Qi Chen2, Peilu Liu2, Christine M. Howison1, Kyle M. Jones1, and Mark D. Pagel1,2
1Department of Biomedical Engineering, University of Arizona, Tucson, Arizona, United States, 2Department of Chemistry & Biochemistry, University of Arizona, Tucson, Arizona, United States

AcidoCEST MRI contrast agents (CA) iopromide (UltravistTM, Bayer Health Care, Inc.®) and iopamidol (IsovueTM, Bracco Imaging, Inc.®) show similar imaging characteristics with respect to excitation pulse, method of frequency encoding, and effects CA concentration, T1 time , and temperature. Iopromide shows better CEST dynamic range for measuring pH, while iopamidol shows better precision. Both contrast agents can be used to measure extracellular pH in vivo.

3319.   53 Intracellular pH Measurement by AACID-CEST MRI at 9.4T: Imaging brain tumor-selective acidification by lonidamine
Nevin McVicar1,2, Alex X Li2, Susan Meakin2,3, and Robert Bartha1,2
1Medical Biophysics, University of Western Ontario, London, Ontario, Canada, 2Robarts Research Institute, Ontario, Canada, 3Biochemistry, University of Western Ontario, London, Ontario, Canada

Lonidamine is an anticancer drug that selectively decreases intracellular pH in tumor cells. A ratiometric CEST approach called amine/amide concentration independent detection (AACID) was recently developed to measure absolute intracellular pH in vivo using MRI. In this study, we produce pH maps before and ~1-2 hour after injection of lonidamine and then immediately post mortem in a brain tumor mouse model. Results show that lonidamine exclusively decreases tumor intracellular pH by ~0.2 pH units and AACID is capable of mapping local changes in brain tumor pH in vivo.

3320.   54 Validation of APT as a measure of pH by 31P in a piglet model of HIE
Marilena Rega1, Francisco Torrealdea1, Alan Bainbridge2, David L Price2, Magdalena Sokolska1, Kevin Broad3, Go Kawano3, Mojgan Ezatti3, Igor Fierrens3, Aaron Oliver-Taylor1, Christina Uria-Avellanal3, Simon Walker-Samuel4, David L Thomas1, Nikola Robertson3, and Xavier Golay1
1Institute of Neurology, UCL, London, London, United Kingdom, 2UCLH, London, United Kingdom, 3Institute for woman's health, UCLH, London, United Kingdom, 4Centre for Advance Biomedical Imaging, UCL, London, United Kingdom

The present work demonstrates the use of APT-MRI as a measure of local pH changes in a model of Hypoxia ischemia insult in the piglet brain. 31P MRS confirms the pH response seen with APT. This work highlights the advantage of spatial information from local pH variations, which may vary across the brain. This technique has the potential to be used in the clinic to map local pH changes and assess treatment effectiveness in newborns suffering from asphyxiation during birth.

3321.   55 31P Magnetic Resonance Spectroscopy and amide proton transfer-Chemical Exchange Saturation Transfer based probes for intracellular pH measurements at 7 tesla
Vitaliy Khlebnikov1, Jannie Wijnen1, Michel Italiaander2, Alex Bhogal1, Hans Hoogduin1, and Dennis Klomp1
1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, 2MR Coils BV, Drunen, Netherlands

Poor spatial resolution is the main limitation of phosphorous-31 MRS for intracellular pH (pHi) quantification. A new method for measuring pHi with high spatial resolution is desired. The feasibility of amide proton transfer (APT) pHi measurements was already demonstrated. However, pHi sensitivity of APT was not addressed. To the end, we therefore propose a setup that combines accurate but low resolution 31P MSR with high resolution chemical exchange saturation transfer (CEST) in the quantification of pHi, using the higher spectral resolution and SNR of 7T. The findings of the study suggest that APT contrast is highly pHi sensitive and can be quantified using 31P MRS in the same subject.

3322.   56 The Amine CEST Feature as a Biomarker of Apoptosis
Martin Durant1, Sharon Portnoy2, Kimberly L Desmond1, Claudia Dziegielewski2, Martin P. Stanisz2, Anne L Martel1,2, and Greg J. Stanisz1,2
1Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2Sunnybrook Research Institute, Toronto, Ontario, Canada

Apoptosis was investigated using Chemical Exchange Saturation Transfer (CEST). Samples of Acute Myeloid Leukemia cells were scanned at 7T, half treated with cisplatin, and half as the untreated control, with CEST offset frequencies -3000-3000Hz. The most notable difference is seen in the Amine feature (~2ppm offset), which is clearly seen in the control, but absent in the treated spectra. A simple "relative area" measure is used to quantify the change, which is highly significant. Some speculation on the possible causes is given. CEST spectroscopy thus may enable monitoring of response to agents such as cisplatin.

3323.   57 APT-CEST and NOE imaging of C6 Glioma cell cultures at 7T
Mona Salehi Ravesh1, Judith Becker1,2, Kristin Koetz1, Amir Moussavi1, Gabriele Trompke1, Kirsten Hattermann2, and Susann Boretius1
1Section Biomedical Imaging, Department of Radiology and Neuroradiology, Christian-Albrechts-University, Kiel, Schleswig Holstein, Germany,2Anatomical Institute, Christian-Albrechts-University, Kiel, Schleswig Holstein, Germany

Recently interesting amide proton transfer (APT) and nuclear overhause enhancement (NOE) effects were reported from in vivo studies in brain tumors. Here, we wanted to investigate, whether we could reproduce these effects in isolated glioma cells. Comparison of C6 z-spectra with z-spectra of nutrient components indicated that the observed asymmetry was mainly caused by the glucose and fetal bovine serum containing nutrition solution rather than specific metabolic products of the tumor cells. The APT and NOE effects observed in vivo may therefore require a tumor-stoma interaction.

3324.   58 Selective Detection of Chemical Exchange Specific R1lower case Greek rho by iTIP gagCEST
Wen Ling1, Francesca J. Nicholls1,2, Tao Jin1, Rob Hartman3, Nam Vo3, Gwendolyn Sowa3, James Kang3, Michel Modo1, and Kyongtae Ty Bae1
1Dept. of Radiology, UPMC, Pittsburgh, PA, United States, 2Dept. of Neuroscience, King’s College London, London, United Kingdom, 3Dept. of Orthopaedic Surgery, UPMC, Pittsburgh, PA, United States

The implementation iTIP gagCEST on cartilaginous tissue has been simulated, and experimentally conducted on phantoms and a rabbit disc. The results from simulation and phantom have clearly demonstrated that iTIP gagCEST can quantitatively measure chemical exchange specific R1 that linearly increases with PG concentration.

3325.   59 Chemical Exchange Saturation Transfer (CEST) and Nuclear Overhauser Effect (NOE) in Blood
Shaokuan Zheng1, Guoxing Lin2, Kajo van der Marel1, Zhongliang Zu3, Yansong Zhao4, and Matthew J Gounis1
1Radiology, 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 blood plasma and red blood cells and subsequently applied Lorentzian fitting of the Z-spectrum, in order to distinguish between the Nuclear Overhauser Effect (NOE) signal arising from aliphatic protons and the CEST signal from exchangeable protons. We found that the NOE effect in the plasma and red blood cells is strong and asymmetric, which may introduce errors in conventional analysis of blood CEST data. The effect of saturation power on the CEST and NOE effect is different, so the saturation power can be optimized to reach a maximum MTRasym.

3326.   60 The signature of protein unfolding in CEST imaging in vitro
Steffen Goerke1, Moritz Zaiss1, Patrick Kunz2, Karel D. Klika3, and Peter Bachert1
1Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany, 2Department of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany, 3Department of Molecular Structure Analysis, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany

Folding states of proteins may have an important contribution to the NOE–mediated contrast in chemical exchange saturation transfer (CEST) imaging of tumors. In 1H NMR experiments with bovine serum albumin (BSA) under different denaturing conditions a characteristic signature of protein folding state in the Z–spectrum was identified. This signature may enable to determine the extent of changes of Z–spectra due to protein unfolding in vivo.

3327.   61 31P MRI of human teeth with Nuclear Overhause Effect enhancement
Yi Sun1, Djaudat Idiyatullin2, Ole Brauckmann3, Donald R. Nixdorf4, Arno Kentgens3, Michael Garwood2, and Arend Heerschap1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands, 2Center for Magnetic Resonance Research, University of Minnesota, MN, United States, 3Institute for Molecules and Materials, Radboud University Nijmegen, Gelderland, Netherlands, 4Department of Diagnostic and Biological Sciences, University of Minnesota, MN, United States

We demonstrate successful 31P MR imaging of human tooth in a reasonable measurement time by BLAST and SWIFT sequences, clearly showing anatomical features in particular dentin, enamel and pulp regions. In agreement with the 31P content the enamel shows the highest and dentin the lower intensity. Furthermore we show that a 1H-31P NOE enhancement of up to 20% can be obtained from dentin, but less than 10% from enamel, in agreement with the water/organic material content. These 31P MR imaging approaches can also be applied to other human mineralized tissue, such as in the diagnosis of osteoporosis.

3328.   62 Innovative method for the detection of T1 agents with MTC- permission withheld
Giuseppe Ferrauto1, Daniela Delli Castelli1, Enza Di Gregorio1, Enzo Terreno1, and Silvio Aime1
1Molecular Biotechnologies & Health Sciences, Molecular Imaging Center, Torino, Italy

In the present work, the possibility to observe the presence of T1 agents by using Magnetization Transfer Contrast (MTC) measurement has been tested since it is well known that MTC depends on the T1 of the tissue. The possibility to observe the same molecule with different MRI sequences will strengthen the evidence of a molecular target when the signal is barely detectable. By looking at the MTC seems to be possible to detect Gd-labeled cells at lower concentration inside a tissue respect to T1 enhancement, especially in the case of compartmentalization of Gd-probe in endosomal vesicles.

63 Novel Quantitative Magnetization Transfer (qMT) of the Human Optic Nerve in vivo.
Alex K Smith1,2, Richard D Dortch2,3, and Seth A Smith2,3
1Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, 2Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, 3Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States

Optic nerve damage is related to the eventual development of MS, and often results in permanent, visual dysfunction. While qMT has been used to evaluate tissue microstructure in the brain and spinal cord, studies in the optic nerve have been limited due to poor contrast between the optic nerve and surrounding tissue. The Dixon method has been used for fat/water separation; however, it has never been applied to the optic nerve, or for qMT imaging. Here we apply novel qMT utilizing Dixon fat/water separation for accurate quantification of the pool size ratio in the human optic nerve in vivo.

3330.   64 Reproducibility and Sensitivity of Quantitative Magnetization Transfer Imaging in Longitudinal Assessment of Spinal Cord Injuries of Monkey
Feng Wang1,2, Ke Li1,2, Huixin Qi3, Arabinda Mishra1, Chaohui Tang1, Daniel Gochberg1,2, Li Min Chen1,2, and John C. Gore1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, 2Radiology Department, Vanderbilt University, Nashville, TN, United States, 3Psychology Department, Vanderbilt University, Nashville, TN, United States

We optimized acquisition schemes for in vivo quantitative magnetization transfer (qMT) imaging and evaluated the reproducibility and sensitivity of qMT parameters for assessing spinal cord injuries (SCI) of anesthetized squirrel monkeys. The results provided robust and sensitive parameters to the formation of abnormalities around the lesion site after SCI. Those qMT parameters were highly correlated to measures of T1, ADC and MTRasym. MRI findings were in agreement with spinal cord tissue histology. This study can help us understand the formation of tumor, cyst or edema, demyelination, inflammation and gliosis during the healing progress after unilateral dorsal column lesion at cervical spinal cord level.

3331.   65 Quantitative MT provides evidence for neuroinflammation in the brain following Interferon-lower case Greek alpha treatment
Nicholas G Dowell1, Neil A Harrison1, Ella Cooper1, and Mara Cercignani1
1Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Falmer, Brighton and Hove, United Kingdom

There is growing evidence that neuroinflammation has a pathogenic role in psychiatric illness, although the presence of subtle inflammation in the brain has not been widely studied. Inflammation can be induced by the administration of a cytokine such as interferon-alpha and although this inflammation is likely to be present in the brain, conventional MR approaches are not sensitive to such subtle changes. In this study, we use qMT to show that the MT transfer rate (kf) is sensitive to changes in the brain following inflammation with interferon and this may enable the study of the pathogenesis of psychiatric illnesses such as schizophrenia and depression.

3332.   66 Selective Myelin Water Suppression by Direct Saturation
Xu Jiang1,2, Peter van Gelderen1, Jacco A de Zwart1, and Jeff H Duyn1
1AMRI, LFMRI, NINDS, National Institutes of Health, Bethesda, MD, United States, 2Department of Physics, University of Maryland, College Park, MD, United States

The effectiveness of using adiabatic, on resonance, 3600 pulses for myelin water imaging based on pulsed saturation transfer contrast is evaluated. Using multi-component analysis of T2* signal decay at 7T, we demonstrate that adiabatic, on-resonance, 3600 pulses allow a strong (80%) saturation of myelin water, while effects on axonal and interstitial water can be kept below 25%. This high selectivity greatly facilitated saturation transfer kinetics and the visualization of myelin water content.

3333.   67 Effect of Magnetization Transfer on Myelin Water Fraction estimation by Steady-State Techniques
Jing Zhang1 and Alex L MacKay1,2
1Department of Radiology, University of British Columbia, Vancouver, B.C., Canada, 2Department of Physics and Astronomy, University of British Columbia, B.C., Canada

This work is to investigate the effect of magnetization transfer (MT) on myelin water fraction estimation from steady-state technique.

3334.   68 Assessing and Reducing the B1 Dependence of Inhomogeneous Magnetization Transfer
Gopal Varma1, Olivier Girard2, Novena Rangwala1, Guillaume Duhamel2, and David C Alsop1
1Radiology, Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 2CRMBM, CNRS 7339, Aix-Marseille Universite, Marseille, France

The application of Inhomogeneous Magnetization Transfer (IHMT) involves off-resonance saturation pulses, and as such may be affected by RF field miscalibration or non-uniformity. A measure of the B1 dependence from IHMT applied in the brain to a series of volunteers suggests the IHMT contrast saturates at higher powers. These results are used to develop a whole brain IHMT sequence that appears less sensitive to RF field non-uniformity when compared to an existing 3D spoiled gradient-echo IHMT acquisition.

3335.   69 Fast high-resolution whole-brain macromolecular proton fraction mapping using a minimal number of source images
Vasily L. Yarnykh1
1Department of Radiology, University of Washington, Seattle, WA, United States

Macromolecular proton fraction (MPF), a key parameter determining the magnetization transfer (MT) effect, has recently attracted significant interest as a biomarker of myelin. Based on a recently published single-point MPF mapping method, a more time-efficient approach has been developed. The described technique eliminates the need in the image for data normalization by using the synthetic reference image calculated from variable flip angle data. Accordingly, only three source images (T1, proton density-, and MT-weighted) are needed for MPF map reconstruction. Based on this principle, whole-brain 3D MPF maps can be obtained with isotropic 1.25 mm resolution and ~20 minutes scan time.

3336.   70 Iterative optimization method for accelerated acquisition and parameter estimation in quantitative magnetization transfer imaging
Henrik Marschner1, André Pampel1, and Harald E. Möller1
1Nuclear Magnetic Resonance Unit, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Saxony, Germany

We investigate the effect of reducing the total number of measurements in qMTI on the model parameters (qMT parameters) of a binary spin bath. The parameters estimation is driven by artificial neural networks (ANNs). The major goal is to find the minimal number of measurements including their optimal settings while maintaining quality and quantitative comparability of the calculated qMT parameters as obtained from a much higher number of measurements. A small number of only 5 measurements is mostly sufficient for the presented experiments with limited saturation parameters. Further spread of the saturation parameters may lead to 4 overall sufficient measurements.

3337.   71 High Resolution, Motion Corrected Mapping of Macromolecular Proton Fraction (MPF) In Clinically Acceptable Time Using 3D Undersampled Radials
Alexey Samsonov1, Pouria Mossahebi2, Ashley Anderson3, Julia Velikina4, Kevin M. Johnson4, Sterling C Johnson5, John O Fleming6, and Aaron Field7
1Radiology, University of Wisconsin, Madison, United States, United States, 2Biomedical Engineering, University of Wisconsin, Madison, United States, United States, 3Medical Physics, University of Wisconsin, Madison, WI, United States, 4Medical Physics, University of Wisconsin, Madison, Wisconsin, United States, 5Medicine, University of Wisconsin, Madison, Wisconsin, United States, 6Neurology, University of Wisconsin, Madison, Wisconsin, United States, 7Radiology, University of Wisconsin, Madison, Wisconsin, United States

Two-pool modeling of magnetization transfer (MT) effects yields a unique set of measures sensitive to different tissue composition properties. The key parameter of interest in this model is a macromolecular pool fraction (MPF), a potential biomarker of myelin in neural tissues. However, traditional MPF mapping within clinical scan time is a relatively low-resolution methodology. The purpose of this work was to develop a clinically feasible, high resolution, motion corrected MPF mapping protocol compatible with clinical standards for GM assessment (~1 mm isotropic, under 30 min).

3338.   72 Fat Suppressed Modified Cross Relaxation Imaging of Articular Cartilage using MaTS: Magnetization Transfer Subtraction
Nade Sritanyaratana1, Pouria Mossahebi1, Walter Block1, Alexey Samsonov2, and Richard Kijowski2
1Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, 2Radiology, University of Wisconsin-Madison, Madison, WI, United States

Modified Cross relaxation imaging (mCRI) is a quantitative magnetization transfer (MT) technique that has been shown to provide potentially useful information about cartilage degeneration. However, cartilage imaging, especially in clinical settings, typically requires large slice thicknesses (3-4mm) because cartilage’s relatively thin tissue structure demands high in-plane resolution (≈0.5mm). Especially since bone and cartilage are significantly curved structures, this highly anisotropic imaging scheme tends to increase partial voluming, and in the context of quantitative imaging can significantly corrupt parametric maps if not corrected. Thus, we propose a technique that suppresses partial voluming from fat and other MT non-exchanging tissues. The proposed technique also suppresses fat chemical shift artifacts, allowing for lower bandwidth imaging for higher SNR.