Magnetization Transfer & CEST
 

Tuesday 2 June 2015

Richard D. Dortch^1,2, Ke Li^1,2, Daniel F. Gochberg^1,2, John C. Gore^1,2, and Seth A. Smith^1,2
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.

Mathieu Boudreau¹, Nikola Stikov¹, and G. Bruce Pike^2
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.

Valentin H. Prevost¹, Olivier M. Girard¹, Gopal Varma², David C. Alsop², and Guillaume Duhamel^1
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).

Sul-Li Lee¹, Seung Hong Choi², and Sung-Hong Park^1
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.

David ML Lilburn¹, Annette S Cooper¹, Philip Murphy², Christopher DJ Sinclair³, Scott I Semple^1,4, and Robert L Janiczek^2
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.

Marco Battiston¹, Marios C Yiannakas¹, Jia Newcombe², Claudia A M Wheeler-Kingshott¹, and Rebecca S Samson^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, England, United Kingdom, 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 MT_sat, calculated using the Multi-Parameter Mapping technique, is performed both in healthy and MS post-mortem spinal cord samples.

Khaoula Bouazizi-Verdier¹ and Geneviève Guillot^1
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.

Xiao-Yong Zhang¹, Jingping Xie¹, Hua Li¹, Junzhong Xu¹, John C. Gore¹, and Zhongliang Zu^1
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.

Geneviève Guillot¹, Sarah Risquez¹, Chih-Ying Wang¹, Jean-Baptiste Galey², Marion Ghibaudo², and Bernard Querleux^2
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.

Ziqi Chen¹, Huawei Zhang¹, Zhiyun Jia^1,2, Jingjie Zhong³, Xiaoqi Huang¹, Mingying Du¹, Lizhou Chen¹, Weihong Kuang⁴, John A Sweeney⁵, and Qiyong Gong^1
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.

Simon Shah¹, Nicolas Geades¹, Andrew Peters¹, Penny Gowland¹, and Olivier Mougin^1
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.

Sugil Kim^1,2 and Jaeseok Park^3
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.

Nirbhay N. Yadav^1,2, Kannie W. Y. Chan^1,2, Monica Pearl¹, Piotr Walczak¹, Miroslaw Janowski^1,3, Peter C. M. van Zijl^1,2, and Michael T. McMahon^1,2
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.

Xiaolei Song^1,2, Xiaowei He¹, Jiadi Xu^1,2, Nikita Oskolkov¹, Nirbhy Yadav^1,2, Peter C.M. van Zijl¹, and Michael T. McMahon^1
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.

Jan-Eric Meissner^1,2, Moritz Zaiss¹, Eugenia Rerich¹, and Peter Bachert^1
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 f_B , the concentration of exchanging protons, and on their exchange rate k_BA. 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 f_B and k_BA 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.

Hye-Young Heo¹, Yi Zhang¹, Shanshan Jiang¹, Dong-Hoon Lee¹, and Jinyuan Zhou^1
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.

Li Liang¹, Jing Yuan², Jiadi Xu³, and Heather T. Ma^1,4
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.

Edward A. Randtke¹, Mark D. Pagel¹, and Julio Cárdenas-Rodríguez^1
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.

Luis A. Montano¹, Mark D. Pagel^2,3, and Julio Cárdenas-Rodríguez^2
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.

Xiaolei Song^1,2, Piotr Walczak^1,2, Xing Yang¹, Xiaowei He^1,3, Jeff W.M. Bulte^1,2, Monica Pearl¹, Peter C.M. van Zijl^1,2, Martin Pomper¹, Michael T. McMahon^1,2, and Mirosław Janowski^1,4
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.

Wei Hu¹, Phillip Zhe Sun², and Renhua Wu^3
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.

Kamini Yogesh Marathe^1,2, Nevin McVicar^1,2, Alex Li², Mojmir Suchy³, Miranda Bellyou², Susan Meakin^2,4, and Robert Bartha^1,2
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.

Kevin Ray¹, James Larkin¹, Yee Kai Tee^2,3, Alexandr Khrapitchev¹, Michael Chappell³, and Nicola Sibson^1
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.

Dong-Hoon Lee¹, Xiaoguang Liu², Kai Zhang¹, Yi Zhang¹, Hye-Young Heo¹, Wenxiao Li¹, Raymond C. Koehler², and Jinyuan Zhou^1
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.

Kevin D'Aquilla¹, Rong Zhou¹, Hari Hariharan¹, Neil Wilson¹, and Ravinder Reddy^1
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.

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 Reddy^1
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.

Annika Busch¹, Dominik Kentrup², Helga Pawelski², Nirbhay N. Yadav^3,4, Guanshu Liu^3,4, Peter C.M. van Zijl^3,4, Stefan Reuter², and Verena Hoerr^1,5
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.

Xiang Xu^1,2, Kannie WY Chan^1,2, Linda Knutsson³, Dmitri Artemov^1,4, Jiadi Xu^1,2, Guanshu Liu^1,2, Yoshi Kato^1,4, Bachchu Lal^5,6, John Laterra^5,6, Michael T McMahon^1,2, and Peter van Zijl^1,2
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: pvanzijl@mri.jhu.edu; kanniec@mri.jhu.edu

Scott William Thalman^1,2, Zhengshi Yang¹, Andrea Mattingly¹, and Moriel Vandsburger^1,3
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.

Xin Chen¹, Weibo Chen^2,3, Guangbin Wang¹, Jianhua Lu⁴, Jinyuan Zhou⁵, Guang Jia^4,6, and Jianqi Li^3
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.

Sujith V Sajja^1,2, Guanshu Liu^1,3, Nirbhay Yadav^1,3, Jiadi Xu³, Antje Arnold^1,2, Anna Jablonska^1,2, Michael McMahon^1,3, Peter van Zijl^1,3, Jeff Bulte^1,2, Piotr Walczak^1,4, and Miroslaw Janowski^1,5
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.

Dong-Hoon Lee¹, Hye-Young Heo¹, Kai Zhang¹, Yi Zhang¹, Shanshan Jiang¹, and Jinyuan Zhou^1
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.

Sung Soo Ahn¹, Yoon Seong Choi¹, Ha-Kyu Jeong², Jinyuan Zhou³, Yansong Zhao⁴, and Seung-Koo Lee^1
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.

Johannes Windschuh¹, Steffen Goerke¹, Jan-Eric Meissner¹, Alexander Radbruch^2,3, Peter Bachert¹, and Moritz Zaiss^1
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 MTR_asym.

Giuseppe Ferrauto¹, Enza Di Gregorio¹, Simona Baroni¹, and Silvio Aime^1
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.