ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Traditional Poster Session • Magnetization Transfer
1740 -1774 Magnetization Transfer & CEST

Tuesday 2 June 2015
Exhibition Hall 13:30 - 15:30

1740.   Optimization of Selective Inversion Recovery Magnetization Transfer Imaging for Clinical Applications
Richard D. Dortch1,2, Ke Li1,2, Daniel F. Gochberg1,2, John C. Gore1,2, and Seth A. Smith1,2
1Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 2Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States

The goal of this work was to optimize a selective inversion recovery (SIR) quantitative magnetization transfer protocol for efficient mapping of myelin content. To do this, we performed numerical studies to: i) find optimal sampling strategies and ii) test whether the MT rate could be held constant during analysis (to reduce the number of images required to invert the model). Results in phantoms and healthy brain demonstrate that SIR parameters can be efficiently and accurately estimated from as few as four optimized SIR images. This suggests that optimized SIR protocols may be viable for clinical applications in the future.

1741.   B1-Sensitivity Analysis of qMT
Mathieu Boudreau1, Nikola Stikov1, and G. Bruce Pike2
1McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, 2Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

B1 mapping is an important measurement used in qMT imaging. For pulsed SPGR qMT imaging experiments, B1 maps are used as a corrective factor for the excitation flip angle and MT saturation. Inaccuracies in B1 mapping will propagate to the fitted qMT parameters differently, depending on the B1-dependence of the T1 mapping method. Here we present a simulation-based analysis of the B1-sensitivity of qMT, comparing how different T1 mapping methods (VFA, IR) propagate the B1 error to the qMT parameters. We show that the pool-size ratio F is very robust to B1 inaccuracies for VFA, as opposed to IR.

1742.   Magnetization Transfer from Inhomogeneously Broadened Lines (ihMT): sequence optimization for preclinical investigation at very high magnetic field (11.75T)
Valentin H. Prevost1, Olivier M. Girard1, Gopal Varma2, David C. Alsop2, and Guillaume Duhamel1
1CRMBM CNRS UMR 7339, Aix-Marseille University, Marseille, France, 2Departement of radiology, BIDMC, Harvard Medical School, Boston, MA, United States

Inhomogeneous magnetization transfer (ihMT) imaging has been recently proposed as new technique for white matter imaging. Whereas its feasibility for small animal studies has been demonstrated, optimization of the ihMT signal and contrast is required. This constituted the subject of this work, which presents optimization of a 2D pulsed ihMT technique for preclinical investigation at very high magnetic field (11.75T).

1743.   Modulation of Inter-Slice Frequency Offsets for Magnetization Transfer Ratio Imaging
Sul-Li Lee1, Seung Hong Choi2, and Sung-Hong Park1
1Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea, 2Department of Radiology, Seoul National University College of Medicine, Korea

Recently, an inter-slice MT imaging using bSSFP has been proposed as a new method for MT imaging. To advance the inter-slice MT imaging to quantitative MT, we tested feasibility of modulation of inter-slice frequency offsets by changing RF duration and inter-slice gap. Experimental results showed that MT images from different offset frequencies could be acquired by changing the RF duration and inter-slice gap, which was demonstrated in phantom and in vivo brain. The proposed technique can enable us to acquire MT images at multiple offset frequencies within a reasonable scan time and thus may be useful for quantitative MT.

1744.   Initial experience using Magnetization Transfer with Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (MT-IDEAL) in the abdomen.
David ML Lilburn1, Annette S Cooper1, Philip Murphy2, Christopher DJ Sinclair3, Scott I Semple1,4, and Robert L Janiczek2
1Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, East Lothian, United Kingdom, 2Experimental Medicine Imaging, GlaxoSmithKline, Uxbridge, Middlesex, United Kingdom, 3Institute of Neurology, University College London, London, United Kingdom, 4BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, East Lothian, United Kingdom

Clinical magnetization transfer (MT) imaging within the abdomen has proven to lack sensitivity to detect liver fibrosis, possibly due to the confounding effect of lipid infiltration. Here a new method, which aims to remove the MT dependence on lipid concentration through integration of IDEAL fat/water separation, is employed. This study assesses the feasibility of MT-IDEAL imaging in the abdomen and compares resultant MTR values using standard MT methods and the MT-IDEAL paradigm. It is hoped that this will eventually allow for investigation of pathological changes in fat content and fibrosis within intra-abdominal organs in a wide range of diseases.

1745.   Multi-parameter mapping of post-mortem lumbar spinal cord tissue in multiple sclerosis
Marco Battiston1, Marios C Yiannakas1, Jia Newcombe2, Claudia A M Wheeler-Kingshott1, and Rebecca S Samson1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, 2NeuroResource Tissue Bank, UCL Institute of Neurology, London, England, United Kingdom

Magnetisation Transfer imaging (MTI) methods are used to probe the macromolecular content of tissue, and find their main application in pathologies involving changes in tissue myelin content, such as multiple sclerosis (MS). Among MTI techniques, those defined as semi-quantitative (i.e. model-free) are most commonly used since they are easy to implement and less time consuming, and therefore more clinically feasible. In this work, a comparison between two semi-quantitative indices, the Magnetisation Transfer Ratio (MTR) and MTsat, calculated using the Multi-Parameter Mapping technique, is performed both in healthy and MS post-mortem spinal cord samples.

1746.   Cross-relaxation parameter quantification in cortical bone from repeated binomial excitations
Khaoula Bouazizi-Verdier1 and Geneviève Guillot1
1IR4M, UMR8081, CNRS, Univ. Paris-Sud, Orsay, France

Evidence of Magnetization Transfer was recently shown in cortical bone between collagen-bound water protons and collagen methylene protons, as well as a correlation between the amount of collagen methylene protons and mechanical properties. It is then important to quantify cross-relaxation parameters. Our purpose was to highlight Magnetization Transfer using inversion-recovery at two RF durations and repeated binomial excitation. The amount of collagen methylene protons assessed by simulation from the repeated binomial excitation data was in agreement with literature. A repeated binomial excitation can be easily integrated into a UTE sequence and should be used for quantitative Magnetization Transfer in vivo.

1747.   Assessment of membrane fluidity using nuclear Overhauser enhancement mediated magnetization transfer
Xiao-Yong Zhang1, Jingping Xie1, Hua Li1, Junzhong Xu1, John C. Gore1, and Zhongliang Zu1
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States

The fluidity of cell membrane is an important characteristic to assess, but to date there are no ways to measure fluidity non-invasively in vivo. We have observed a novel source of contrast at around -1.6 ppm in z-spectra which is derived from nuclear Overhauser enhancement (NOE) effects between water protons and choline methyl protons which are in a restricted state within cell membranes. Our measurements of this signal modulation in different conditions show that NOE-mediated MT signal correlates well with membrane fluidity. This may provide a novel and non-invasive imaging tool to assess changes in membrane fluidity.

1748.   Bound water in reconstructed skin samples: quantification by NMR
Geneviève Guillot1, Sarah Risquez1, Chih-Ying Wang1, Jean-Baptiste Galey2, Marion Ghibaudo2, and Bernard Querleux2
1CNRS Univ Paris-Sud, IR4M UMR8081, ORSAY, France, 2L'Oreal Research & Innovation, AULNAY-SOUS-BOIS, France

Reconstructed skin samples are routinely used for in vitro safety and efficacy evaluation of cosmetic ingredients. MT-NMR is well-suited as a non-destructive technique for the quantification of the bound proton fraction. In this work, an off-resonance MT-NMR sequence was used to characterize dermis from reconstructed skin samples. A linear relationship between the bound proton fraction and the solid weight fraction was found with a slope compatible with 0.2 g of bound water per g of collagen, in fair agreement with the 4 water molecules per tripeptide description of collagen hydration.

1749.   Magnetization Transfer Imaging of Suicidal Patients with Major Depressive Disorder
Ziqi Chen1, Huawei Zhang1, Zhiyun Jia1,2, Jingjie Zhong3, Xiaoqi Huang1, Mingying Du1, Lizhou Chen1, Weihong Kuang4, John A Sweeney5, and Qiyong Gong1
1Huaxi MR Research Center (HMRRC), Department of Radiology,West China Hospital of Sichuan University, Chengdu, Sichuan, China, 2Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China, 3Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, China, 4Department of Psychiatry, State Key Lab of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China, 5Departments of Psychiatry and Pediatrics, University of Texas Southwestern, Texas, United States

We utilized magnetization transfer imaging to identify subtle biophysical alterations in MDD with suicidal behavior. The participants were 36 medication-free MDD patients, with (N = 17) and without (N = 19) a history of suicide attempt, and 28 healthy controls. Magnetization transfer ratio (MTR) was decreased in the left inferior parietal lobule (IPL) and right superior parietal lobule (SPL) in suicide attempters relative to non-attempters and controls. Non-attempters showed reduced MTR in left IPL and left cerebellum relative to controls. Attentional dysfunction and impaired decision making secondary to parietal lobe abnormalities could increase risk for suicidal behavior in MDD.

1750.   Eliminating MT Contribution in Z-Spectra using Dual Band Macromolecular Background Suppression (DBMS)
Simon Shah1, Nicolas Geades1, Andrew Peters1, Penny Gowland1, and Olivier Mougin1
1Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Chemical Exchange Saturation Transfer (CEST) and Nuclear Overhauser Enhancement (NOE) effects have the potential to transform MRI into a molecular imaging technique. Dual band macromolecular background suppression (DBMS) pulses are designed to saturate two RF frequencies simultaneously. One of the frequency bands provides suppression of the macromolecular contribution across the whole z-spectrum whilst the other sweeps the Z-spectrum. DBMS provides a method to uncouple MT effects from other features of the z-spectrum which will simplify quantification and separation of different z-spectrum features.

1751.   Spiral-CEST Encoding with Spectral and Spatial B0 Correction
Sugil Kim1,2 and Jaeseok Park3
1Department of Brain and Cognitive Engineering, Korea University, Seoul, Korea, 2Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Sungkyunkwan University, Suwon, Korea, 3Biomedical Imaging and Engineering Lab., Department of Global Biomedical Engineering, Sungkyunkwan University, Suwon, Korea

Chemical exchange saturation transfer (CEST), which exploits saturation transfer induced proton exchange and its corresponding, indirect loss of water signals, has been shown to provide a novel contrast mechanism in MRI [1,2]. However, CEST MRI is highly vulnerable to magnetic field inhomogeneities. To address this problem, it often requires multi-spectral acquisitions (z-spectrum), and hence leads to prohibitively long imaging time [3]. In this work, we propose Spiral-CEST encoding with spectral and spatial B0 correction under the hypothesis that in the presence of magnetic field inhomogeneities spiral encoding induced image blurring in the spatial dimension makes no contribution to a DC frequency shift in the z-spectral dimension due to the spatially, slowly varying field map.

1752.   Retrospective motion correction in CEST MRI data using time domain analysis
Nirbhay N. Yadav1,2, Kannie W. Y. Chan1,2, Monica Pearl1, Piotr Walczak1, Miroslaw Janowski1,3, Peter C. M. van Zijl1,2, and Michael T. McMahon1,2
1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, 2FM Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States, 3NeuroRepair Department, MMRC, PAS, Warsaw, Poland

Abdominal motion has limited the number CEST MRI studies in the body since signal fluctuations can be an order of magnitude larger than the CEST signal. Using simulated data and also data from experiments where arginine capsules where injected into live swine, we show how motion effects in z-spectra can be significantly reduced retrospectively using time-domain analysis.

1753.   A Multi-parametric Multi-echo Saturation (MMS) method enabling CEST fingerprinting
Xiaolei Song1,2, Xiaowei He1, Jiadi Xu1,2, Nikita Oskolkov1, Nirbhy Yadav1,2, Peter C.M. van Zijl1, and Michael T. McMahon1
1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

CEST contrast varies as a function of saturation power (B1) and length (tsat), offering the opportunities for creating the CEST fingerprint for various agents. We proposed a Multi-parametric Multi-echo Saturation (MMS) method, enabling the acquisition of multiple readouts with alternating B1. This so-called hybrid meLOVARS method generates both B1 and tsat dependent profiles, with the goal of improving specificity to exchange rate. This sequence enabled fast acquisition of multi-parametric saturation-weighted images, and allowed separation of different pH solutions according to their specific saturation-modulation patterns. It also has potentials in vivo for modulating different saturation contrasts and increase the specificity.

1754.   Quantitative CEST (qCEST) using Ω–plots in the case of trains of Gaussian–shaped saturation pulses
Jan-Eric Meissner1,2, Moritz Zaiss1, Eugenia Rerich1, and Peter Bachert1
1Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany, 2Neurooncologic Imaging, Division of Radiology, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany

The contrast in CEST experiments depends on fB , the concentration of exchanging protons, and on their exchange rate kBA. The Ω-plot method is able to quantify both simultaneously in the case of cw saturation. We show that AREX, generating the CEST contrast in a cw experiment, can be extended to the case of pulsed CEST. This extension allows to define an Ω–plot method yielding improved estimation of fB and kBA also in the case of saturation by a train of Gaussian–shaped rf pulses. This approach could be the next step towards quantitative CEST studies in vivo.

1755.   Quantitative Assessment of Amide Proton Transfer (APT) and Nuclear Overhauser Enhancement (NOE) Imaging with Extrapolated Semi-solid Magnetization Transfer Reference (EMR) Signals - an Accurate and Straightforward Measurement Approach
Hye-Young Heo1, Yi Zhang1, Shanshan Jiang1, Dong-Hoon Lee1, and Jinyuan Zhou1
1Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States

APT imaging is important molecular MRI technique that detect endogenous mobile proteins in tissue, such as those in the cytoplasm. To quantitatively assess APT and NOE effects in vivo, a new fitting approach has been introduced, which is based on the extrapolated semi-solid MT model reference signals. The quantitative APT and NOE signals were measured and compared with the commonly used MTRasym(3.5ppm) in human glioma at 3 Tesla. The quantitative results showed that APT signals were significantly higher in the glioma than in the normal tissue and edema, and were the major contributor to the APT-weighted image contrast.

1756.   Optimal Sampling Schedule for PARACEST Agents and Analysis of its Performance
Li Liang1, Jing Yuan2, Jiadi Xu3, and Heather T. Ma1,4
1Department of Electronic and Information Engineering, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, Guangdong, China, 2Medical physics and research department, Hong Kong Sanatorium & Hospital, Hong Kong, 3F. M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States, 4Radiology Department, Johns Hopkins University, Baltimore, MD, United States

This study proposed an optimal sampling schedule (OSS) for PARACEST agents and simulations were conducted to verify its performance. OSS was calculated by simplified algorithm associated with average sensitivity curves. Simulations were performed by fitting noisy z spectra generated according to prior distribution of model parameters. Results show that there is a connection between the performance of OSS and the distribution of true values of model parameters. The OSS method is able to provide more accurate parameters comparing to evenly distributed sampling (EDS) scheme even in the very low sample number range.

1757.   Improved diagnosis of tumor tissues with QUESPOWR MRI
Edward A. Randtke1, Mark D. Pagel1, and Julio Cárdenas-Rodríguez1
1Biomedical Engineering, University of Arizona, Tucson, AZ, United States

The Quantification of Exchange as a function of Saturation Power On the Water Resonance (QUESPOWR) method is introduced as a simple way to detect tissues with fast exchanging labile protons with small chemical shifts relative to water. QUESPOWR is analyzed by the linear HP-HW-QUESP method. Simulations and in vivo studies showed that QUESPOWR contrast is specific for tissues that exhibit low extracellular pH. QUESPOWR might offer sensitivity and specificity for tumor diagnosis.

1758.   Quantum Chemical Prediction and Experimental Validation of the Characteristics of diaCEST MRI Contrast Agents
Luis A. Montano1, Mark D. Pagel2,3, and Julio Cárdenas-Rodríguez2
1Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, United States, 2Biomedical Engineering, University of Arizona, Tucson, Arizona, United States, 3Arizona Cancer Center, University of Arizona, Tucson, Arizona, United States

We have developed a new method based on computational quantum chemistry that predicts potential diaCEST MRI contrast agents. Using the gauge invariant atomic orbital (GIAO) method, density functional theory (DFT), and quantum theory of atoms in molecules (QTAIM), offset frequencies for CEST agents can be predicted within 0.2 to 0.3 ppm chemical shift difference, and predict whether or not the agent will show CEST effect based on the density of the hydrogen bond. These results demonstrate that computational quantum chemistry can be applied to MRI research and contrast agents can be predicted before being tested experimentally in pre-clinical and clinical MRI scanners.

1759.   Salicylic Acid based CEST agents for assessing brain perfusion territory and blood-brain barrier permeability
Xiaolei Song1,2, Piotr Walczak1,2, Xing Yang1, Xiaowei He1,3, Jeff W.M. Bulte1,2, Monica Pearl1, Peter C.M. van Zijl1,2, Martin Pomper1, Michael T. McMahon1,2, and Mirosław Janowski1,4
1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3School of Information Sciences and Technology, Northwest University, Xi'an, Shaanxi, China, 4NeuroRepair Department, MMRC, PAS, Warsaw, Poland

We used aspirin analogues as CEST contrast agents for visualizing transcatheter brain perfusion territory. During intra-arterial infusion of these contrast agents, perfused brain parenchyma was highlighted in CEST images, with the contrast quickly dropping to baseline after infusion discontinuation. Three aspirin analogues with distinct chemical shifts were evaluated. They were detectable with the dose of ~11mg/kg producing >5% contrast.. Upon intra-arterial infusion of high osmolality mannitol, BBB disruption and parenchymal retention of contrast agents was observed with the territory matching that highlighted by control Gd-DTPA. When subsequently infusing two agents, multi-color CEST imaging allowed differentiation of their perfusion territories.

1760.   Iopamidol CEST for pH mapping on a 7T scanner: phantom and normal mice kidneys in vivo study
Wei Hu1, Phillip Zhe Sun2, and Renhua Wu3
1the Second Affiliated Hospital of Shantou University Medical College, Shangtou, GuangDong, China, 2Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, 3Shantou University Medical College, Shantou, Guangdong, China

Human tissue lesions are often associated with cell internal and external disturbance of pH, and most of them showed the pHe value decreased .1 Therefore the determination of pHe in the tissue will have certain value for early diagnosis and identify of diseases. Up to now, the Iopamidol as a CEST imaging contrast agents have been reported.1-3 The aim of this study was to measure pH in vitro and in normal mice kidneys with Iopamidol use a new method and more simple ratiometric method on a 7T scanner3.

1761.   Topiramate Induced Intracellular Acidification in Brain Tumors: In-vivo Detection Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging
Kamini Yogesh Marathe1,2, Nevin McVicar1,2, Alex Li2, Mojmir Suchy3, Miranda Bellyou2, Susan Meakin2,4, and Robert Bartha1,2
1Medical Biophysics, Western University, London, Ontario, Canada, 2Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada, 3Chemistry, Western University, London, Ontario, Canada, 4Biochemistry, Western University, London, Ontario, Canada

Lonidamine which is previously used to quantify tumor selective acidification (decrease in intracellular pH(pHi)), using a novel chemical exchange saturation (CEST) method called amine and amide independent detection (AACID) CEST, is currently not approved to use in humans. Present study uses the antiepileptic drug, Topiramate, to quantify tumor selective acidification using AACID method in mouse model of cancer. After a single dose of topiramate, significant decrease in tumor pHi was evident. Further study on tumor selective acidification by topiramate is needed to determine whether AACID/CEST effects can be used for tumor detection and monitoring tumor response to treatment.

1762.   Sensitivity of CEST MRI for absolute pH measurement in brain metastases
Kevin Ray1, James Larkin1, Yee Kai Tee2,3, Alexandr Khrapitchev1, Michael Chappell3, and Nicola Sibson1
1CRUK and MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom, 2Department of Mechatronics and Biomedical Engineering, Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Kuala Lumpur, Malaysia, 3Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom

CEST-MRI has emerged as a potential in vivo pH measurement method, but several confounding factors make absolute pH mapping difficult. Non-invasive mapping of pH would be useful in the clinic, particularly in the treatment of brain metastases. We aimed to determine the sensitivity of CEST to changes in pH, proton concentration, T1 and T2 in phantom models of mouse brain and metastatic breast tumour cells. Three analyses were used to measure CEST effects, and comparisons drawn. PTR* was found to be the most sensitive analysis metric, with the potential to measure pH changes on the order of 0.1pH units.

1763.   Quantitative Measurements of Amide Proton Transfer (APT) Signals and Tissue pH in Acute Ischemic Stroke
Dong-Hoon Lee1, Xiaoguang Liu2, Kai Zhang1, Yi Zhang1, Hye-Young Heo1, Wenxiao Li1, Raymond C. Koehler2, and Jinyuan Zhou1
1Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, 2Department of Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

APT imaging can be used to obtain tissue pH information. In this abstract, the quantitative measurements of APT signals and tissue pH in the acute ischemic stroke in rats were performed using extrapolated semi-solid magnetization transfer reference (EMR) signals. Our EMR approach may be helpful for more accurate APT pH quantification, and useful to understand and identify the characteristics of the ischemic stroke tissue.

1764.   31P MRS and Creatine CEST: A Method to Monitor Creatine Kinase Metabolism in a Perfused Heart Model
Kevin D'Aquilla1, Rong Zhou1, Hari Hariharan1, Neil Wilson1, and Ravinder Reddy1
1Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

Creatine Chemical Exchange Saturation Transfer (CrCEST), in conjunction with traditional 31P MRS methods, has recently been shown to be able to evaluate the activity of creatine kinase in the human calf muscle. Although study of cardiac bioenergetics using CrCEST is an enticing prospect, a number of difficulties exist in translating this method to the human heart in vivo. This work, utilizing an ex vivo perfused rat heart model at 9.4T, represents a preliminary step towards applying CrCEST to the study of cardiac metabolism, including the heart's response to ischemia, infarction, and adverse biochemical and physical stressors.

1765.   Glutamate CEST MRI in MPTP Mouse Model of Parkinson’s Disease
Puneet Bagga1, Rachelle Crescenzi1, Guruprasad Krishnamoorthy1, Ravi Prakash Reddy Nanga1, Sidyarth Garimall1, Kevin D’Aquilla1, Damodara Reddy1, Joel H Greenberg2, John A Detre2, Hari Hariharan1, and Ravinder Reddy1
1Department of Radiology, University of Pennsyvania, Philadelphia, Pennsylvania, United States, 2Department of Neurology, University of Pennsyvania, Philadelphia, Pennsylvania, United States

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes selective dopaminergic death in the substantia nigra and is used as an animal model for Parkinson’s disease (PD). Recent studies have shown that exchangeable amine protons on glutamate (Glu) exhibit a concentration dependent chemical exchange saturation transfer (CEST) effect with surrounding water protons (GluCEST). Here, we apply GluCEST, a novel non-invasive MRI technique, in an MPTP mouse model of PD. GluCEST imaging demonstrates ~13% elevation in GluCEST contrast in striatum of PD mice in agreement with 1H MR spectroscopy.

1766.   GlucoCEST as method for early detection of renal allograft rejection
Annika Busch1, Dominik Kentrup2, Helga Pawelski2, Nirbhay N. Yadav3,4, Guanshu Liu3,4, Peter C.M. van Zijl3,4, Stefan Reuter2, and Verena Hoerr1,5
1Department of Clinical Radiology, University Hospital Muenster, Muenster, Germany, 2Department of Medicine D - Experimental Nephrology, University Hospital Muenster, Muenster, Germany, 3Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, 4F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, United States, 5Institute of Medical Microbiology, Jena University Hospital, Jena, Germany

In this small animal study we implemented and validated glucoCEST MRI for early detection and diagnosis of renal allograft rejection in a rat model. By using an optimized glucose infusion protocol which led to an increased and constant blood glucose level over MR measurement time, we obtained increased CEST contrast in pelvis and cortex for renal allografts undergoing rejection on day four post transplantation, compared to native kidneys. Calculated CEST-intensity ratios of transplanted and native kidneys were in good agreement with data of previous PET studies.

1767.   Dynamic Glucose Enhanced (DGE) MRI for Imaging Brain Cancer
Xiang Xu1,2, Kannie WY Chan1,2, Linda Knutsson3, Dmitri Artemov1,4, Jiadi Xu1,2, Guanshu Liu1,2, Yoshi Kato1,4, Bachchu Lal5,6, John Laterra5,6, Michael T McMahon1,2, and Peter van Zijl1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute Johns Hopkins Medicine, Baltimore, MD, United States, 3Department of Medical Radiation Physics, Lund University, Lund, Sweden, 4Division of Cancer Imaging Research and JHU In Vivo Cellular Molecular Imaging Center, Johns Hopkins Medicine, MD, United States, 5Department of Neurology, Kennedy Krieger Institute, MD, United States, 6Department of Neuroscience, Kennedy Krieger Institute, MD, United States

Altered perfusion and uptake of glucose are hallmarks of tumors and there is a need for MRI methods revealing tumor perfusion, permeability and aggressiveness. We employed chemical exchange saturation transfer (CEST) MRI to dynamically study the delivery and uptake of D-glucose in an orthotopic glioblastoma model and compared this with dynamic contrast enhanced (DCE) MRI with GdDTPA. Dynamic Glucose Enhanced (DGE) data showed a prolonged uptake of glucose in tumors as compared to normal brain tissue, and compared well to DCE in identifying the tumor. The results indicate the feasibility for using D-glucose as an MRI perfusion agent for tumor assessment. #Both authors contributed equally *To whom correspondence may be addressed: Email:;

1768.   Cardiac CEST imaging of diffuse fibrosis
Scott William Thalman1,2, Zhengshi Yang1, Andrea Mattingly1, and Moriel Vandsburger1,3
1Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States, 2Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky, United States, 3Department of Physiology, University of Kentucky, Lexington, Kentucky, United States

Using a novel cardiac chemical exchange saturation transfer (CEST) pulse sequence, we have demonstrated changes in the magnetization transfer ratio (MTR) of diffuse fibrosis in the myocardium of a mouse model of chronic Angiotensin II stimulation. AngII treated mice exhibit reduced levels of MTR (9.64 ± 2.81%) compared to saline treated (19.4 ± 1.99%) and control mice (17.5 ± 3.15%). This is due to an increase in the extracellular water volume that results in reduced magnetization transfer between the matrix macromolecules and bulk water. This technique has the potential to enable gadolinium-free imaging of diffuse fibrosis.

1769.   Breath-hold CEST-MRI of Liver Cirrhosis: A Clinical Feasibility Study
Xin Chen1, Weibo Chen2,3, Guangbin Wang1, Jianhua Lu4, Jinyuan Zhou5, Guang Jia4,6, and Jianqi Li3
1Shangdong Medical Imaging Research Institute, Shangdong University, Jinan, Shandong, China, 2Philips Healthcare, Shanghai, China, 3Shanghai Key Laboratory of Magnetic Resonance and Department of Physics, East China Normal University, Shanghai, China, 4Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, United States, 5Johns Hopkins University, Baltimore, MD, United States, 6Pennington Biomedical Research Center, Baton Rouge, LA, United States

Liver cirrhosis is one type of glycogen storage disease without an increased amount of glycogen. Instead, the glycogen that does build up in the liver has very long outer branches, which may have a significant contribution to the transfer ratio of hydroxyl protons in CEST-MRI measurements. We have shown that it is clinically feasible to obtain CEST spectra in the liver with the breath-hold technique. Liver cirrhosis exhibited a significantly higher MTR at the resonance frequency of hydroxyl protons (1.2ppm), indicating a higher concentration of glycogen outer branches in liver cirrhosis.

1770.   CEST and FLEX MRI for detection of CNS graft rejection
Sujith V Sajja1,2, Guanshu Liu1,3, Nirbhay Yadav1,3, Jiadi Xu3, Antje Arnold1,2, Anna Jablonska1,2, Michael McMahon1,3, Peter van Zijl1,3, Jeff Bulte1,2, Piotr Walczak1,4, and Miroslaw Janowski1,5
1Dept. of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Department of Radiology, University of Warmia and Mazury, Olsztyn, Poland, 5NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

Conventional imaging such T1, T2 has been widely used to study gross anatomical changes and edema in brain. Stem cell transplantation has become attractive for regenerative medicine, but, grafts take months to years to become fully functional and could be rejected during this process. Non-invasive modalities to study CNS graft rejection clinically are currently unavailable. Progress in MR is providing access to molecular level changes including graft rejection process. Here we show that CEST and FLEX MRI may aid in detection of the process of rejection that could be tailored to individual grafts within the paradigm of personalized medicine.

1771.   Effects of Water Proton Concentration and Water T1 Changes on APT and NOE Imaging Signals in Gliomas
Dong-Hoon Lee1, Hye-Young Heo1, Kai Zhang1, Yi Zhang1, Shanshan Jiang1, and Jinyuan Zhou1
1Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Amide proton transfer (APT) imaging can provide endogenous contrast related to the mobile amide proton content, amide proton exchange rate, and several other possible tissue and experimental parameters. Here, the correlations between APT and water proton concentration and T1 were assessed using quantified APT based on the extrapolated semi-solid magnetization transfer reference (EMR) method. The results indicated no significant correlations between APT/NOE signals and the combined effect of water concentration and T1. The observed APT hyper-intensities in tumor are primarily related to the mobile amide proton content and/or the amide proton exchange rate.

1772.   Amide Proton Transfer Imaging in Hemorrhagic Brain Lesions at 3T
Sung Soo Ahn1, Yoon Seong Choi1, Ha-Kyu Jeong2, Jinyuan Zhou3, Yansong Zhao4, and Seung-Koo Lee1
1Radiology, Yonsei University College of Medicine, Seoul, Korea, 2Philips Korea, Seoul, Korea, 3Radiology, Johns Hopkins University, Baltimore, Maryland, United States, 4Philips Healthcare, Cleveland, Ohio, United States

Amide proton transfer imaging was performed in several hemorrhagic brain lesions including glioblastoma, metastasis, and cavernous malformation. We found that magnetic transfer ratio asymmetry in hemorrhage was higher than those in enhancing portion, perilesional T2 hyperintensity, and normal appearing white matter in all patients regardless of underlying pathology. We should be aware of high magnetic tranfer ratio asymmetry in hemorrhage for interpreting brain lesions with hemorrhage.

1773.   Isolated amide proton CEST contrast at 7 T correlates with contrast–enhanced T1–weighted images of tumor patients
Johannes Windschuh1, Steffen Goerke1, Jan-Eric Meissner1, Alexander Radbruch2,3, Peter Bachert1, and Moritz Zaiss1
1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany, 2Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Baden-Württemberg, Germany, 3Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany

We present a method that isolates the in vivo CEST effect of amide protons at 7 T from the underlying aromatic NOE. This results in a contrast solely dependent on pH and amide proton concentration, that shows excellent correlation with the tumor ring enhancement of T1-weighted gadolinium contrast-enhanced images. This is shown for 4 patients with newly diagnosed and histologically proven glioblastoma in comparison to the asymmetry based CEST contrast MTRasym.

1774.   Frequency-Encoded MRI-CEST Agents Based on Paramagnetic Liposomes/RBC Aggregates
Giuseppe Ferrauto1, Enza Di Gregorio1, Simona Baroni1, and Silvio Aime1
1Molecular Biotechnology and Health Science, Molecular Imaging Center-University of Torino (IT), Torino, Italy

Positively charged paramagnetic liposomes have been electrostatically bound to the membrane of RBCs. These aggregates yield two CEST pools represented by liposomal water protons (LipoCEST) and cytoplasmatic water protons (ErythroCEST), respectively. When administrated In vivo intravenously, these aggregates report about the vascular volume ans the residual LipoCEST effect informs about the presence of released liposomes in the tumor region . the LipoCEST/RBC aggregates represent a new way to label cells, a new route to improve the circulation lifetime of the liposomes and a procedure to assess the de-assembly of the aggregates and the accumulation of the liposomes in the tumor.