Olivier E Mougin¹ and Penny A Gowland^1
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.

Qinwei Zhang¹, Yanjie Zhu², Jing Yuan^1,3, Shuzhong Chen¹, Deyond Siu¹, Min Deng¹, Yi-Xiang J Wang¹, and Dong Liang^2
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.

Robert Frost¹, Aaron T. Hess², Nicholas P. Blockley¹, Yee Kai Tee³, Michael A. Chappell^1,3, M. Dylan Tisdall^4,5, Andre J. W. van der Kouwe^4,5, and Peter Jezzard^1
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.

Dapeng Liu^1,2, Rong Xue^1,2, Jinyuan Zhou^3,4, Jing An⁵, Xinyuan Miao¹, and Danny JJ Wang^2,6
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.

Miao Zhang¹, Jianhua Lu¹, Lin Chen¹, Shuhui Cai¹, Congbo Cai¹, and Zhong Chen^1
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.

Hoonjae Lee¹, Chul-Ho Sohn², and Jaeseok Park^1
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.

Gang Xiao¹, Phillip Zhe Sun², Zhuozhi Dai³, and Renhua Wu^3
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.

Daniel James Clark^1,2, Seth A Smith^3,4, and Michael V Knopp^1
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.

Mitsuharu Miyoshi¹, Tsuyoshi Matsuda¹, and Hiroyuki Kabasawa^1
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.

Tao Jin¹ and Seong-Gi Kim^1,2
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 (MTR_asym) analysis of CEST studies removes direct water saturation and other symmetric non-CEST contributions. However, in vivo MTR_asym is still confounded by asymmetric contributions, including magnetization transfer contrast from immobile macromolecules (MTC_IM) 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 MTC_IMand NOE.

Giaime Rancan^1,2, Thi Thoa Nguyen¹, Silvio Aime^2,3, Markus Schwaiger⁴, and Steffen Glaser^1
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.

Eugenia Rerich¹, Moritz Zaiss¹, and Peter Bachert^1
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.

Johannes Windschuh¹, Moritz Zaiss¹, Jan-Eric Meissner¹, and Peter Bachert^1
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 MTR_Rex for spillover correction.

Hua Li¹, Zhongliang Zu¹, Moritz Zaiss², Imad S. Khan³, Robert Singer³, Daniel F. Gochberg¹, Peter Bachert², John C. Gore¹, and Junzhong Xu^1
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.

HA-KYU JEONG¹, SETH SMITH², and HO SUNG KIM^3
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.

Phillip Zhe Sun¹, Gang Xiao², and Renhua Wu^3
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.

Yee Kai Tee¹, George Harston², Nicholas Blockley³, Thomas Okell³, Jacob Levman¹, Martino Cellerini⁴, Fintan Sheerin⁴, Peter Jezzard³, James Kennedy², Stephen Payne¹, and Michael Chappell^1
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.

Jae-Seung Lee^1,2, Ding Xia¹, Yulin Ge¹, Alexej Jershow², and Ravinder Regatte^1
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.

Zhongliang Zu¹, Hua Li¹, Junzhong Xu¹, Daniel F Gochberg¹, and John C Gore^1
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 CERT_ex is described which corrects for such factors and produces images that are more specifically k_sw (and thus pH) dependent. Simulations and experiments show that CERT_ex has better specificity and sensitivity than conventional APT imaging methods for delineating effects of stroke at 9.4 T.

Moriel Vandsburger¹, Katrien Vandoorne², Roni Oren², Avigdor Leftin², and Michal Neeman^2
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.

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 Yuan^1,3
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.

Osamu Togao¹, Takashi Yoshiura¹, Jochen Keupp², Akio Hiwatashi¹, Koji Yamashita¹, Kazufumi Kikuchi¹, Yuriko Suzuki³, Koji Sagiyama⁴, Masaya Takahashi⁴, and Hiroshi Honda^1
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.

Chunmei Li¹, Shuai Peng¹, Rui Wang¹, Haibo Chen¹, Wen Su¹, Xuna Zhao², Jinyuan Zhou³, and Min Chen^1
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.

Julius Juhyun Chung^1,2, Sunyoung Chae^1,2, Moon-sun Jang³, Jae-hun Kim⁴, Geun Ho Im³, Seong-Gi Kim^2,5, and Jung Hee Lee^1,4
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).

Zhongliang Zu¹, Hua Li¹, Junzhong Xu¹, Daniel F Gochberg¹, and John C Gore^1
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.

Zhongliang Zu¹, Hua Li¹, Junzhong Xu¹, Daniel F Gochberg¹, and John C Gore^1
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.

Tao Jin¹ and Seong-Gi Kim^1,2
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.

Brianna F. Moon¹, Liu Qi Chen², Peilu Liu², Christine M. Howison¹, Kyle M. Jones¹, and Mark D. Pagel^1,2
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.

Nevin McVicar^1,2, Alex X Li², Susan Meakin^2,3, and Robert Bartha^1,2
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.

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 Golay^1
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.

Vitaliy Khlebnikov¹, Jannie Wijnen¹, Michel Italiaander², Alex Bhogal¹, Hans Hoogduin¹, and Dennis Klomp^1
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.

Martin Durant¹, Sharon Portnoy², Kimberly L Desmond¹, Claudia Dziegielewski², Martin P. Stanisz², Anne L Martel^1,2, and Greg J. Stanisz^1,2
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.

Mona Salehi Ravesh¹, Judith Becker^1,2, Kristin Koetz¹, Amir Moussavi¹, Gabriele Trompke¹, Kirsten Hattermann², and Susann Boretius^1
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.

Wen Ling¹, Francesca J. Nicholls^1,2, Tao Jin¹, Rob Hartman³, Nam Vo³, Gwendolyn Sowa³, James Kang³, Michel Modo¹, and Kyongtae Ty Bae^1
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.

Shaokuan Zheng¹, Guoxing Lin², Kajo van der Marel¹, Zhongliang Zu³, Yansong Zhao⁴, and Matthew J Gounis^1
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.

Steffen Goerke¹, Moritz Zaiss¹, Patrick Kunz², Karel D. Klika³, and Peter Bachert^1
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.

Yi Sun¹, Djaudat Idiyatullin², Ole Brauckmann³, Donald R. Nixdorf⁴, Arno Kentgens³, Michael Garwood², and Arend Heerschap^1
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.

Giuseppe Ferrauto¹, Daniela Delli Castelli¹, Enza Di Gregorio¹, Enzo Terreno¹, and Silvio Aime^1
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.

Alex K Smith^1,2, Richard D Dortch^2,3, 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, 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.

Feng Wang^1,2, Ke Li^1,2, Huixin Qi³, Arabinda Mishra¹, Chaohui Tang¹, Daniel Gochberg^1,2, Li Min Chen^1,2, and John C. Gore^1,2
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.

Nicholas G Dowell¹, Neil A Harrison¹, Ella Cooper¹, and Mara Cercignani^1
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.

Xu Jiang^1,2, Peter van Gelderen¹, Jacco A de Zwart¹, and Jeff H Duyn^1
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.

Jing Zhang¹ and Alex L MacKay^1,2
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.

Gopal Varma¹, Olivier Girard², Novena Rangwala¹, Guillaume Duhamel², and David C Alsop^1
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.

Vasily L. Yarnykh^1
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.

Henrik Marschner¹, André Pampel¹, and Harald E. Möller^1
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.

Alexey Samsonov¹, Pouria Mossahebi², Ashley Anderson³, Julia Velikina⁴, Kevin M. Johnson⁴, Sterling C Johnson⁵, John O Fleming⁶, and Aaron Field^7
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).

Nade Sritanyaratana¹, Pouria Mossahebi¹, Walter Block¹, Alexey Samsonov², and Richard Kijowski^2
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.