Endogenous Contrast Mechanisms: CEST & Relaxation
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Friday May 13th
Room 511A-C  10:30 - 12:30 Moderators: R. Mark Henkelman and Ravinder Reddy

10:30 704.   Could Lipids Contribute to the Exchange-Induced Resonance Frequency Contrast in Brain Tissue? 
Karin Shmueli1, Stephen J Dodd2, Christian Wunder3, and Jeff H Duyn1
1Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, 2Functional and Molecular Metabolism Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, 3Traffic, Signaling and Delivery Laboratory, Curie Institute, France

Substantial positive white-gray matter (WM-GM) exchange-induced frequency shifts (fx) have been measured in brain tissue. Cerebrosides are proposed to contribute because they are more abundant in WM than GM. We measured fx due to cerebrosides at six concentrations in an in-vitro model for WM cell membranes by performing chemical shift imaging experiments using dioxane as a reference chemical. fx increased linearly with cerebroside concentration (0.18 ppb/mM). Together with the human WM-GM difference in cerebroside content, this suggests that cerebrosides could account for much of the measured WM-GM fx. These findings should aid in interpreting MR frequency contrast.

10:42 705.   Amide proton transfer (APT) MR signal as a novel imaging biomarker for charactering radiation necrosis in rats 
Silun Wang1, Erik Tryggestad2, Michael Armour2, Eric Ford2, Tingting Zhou1, Kun Yan1, Zhibo Wen1, Peter C.M. van Zijl1,3, and Jinyuan Zhou1,3
1Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute

We evaluated radiation-induced necrosis in a rat model (40 Gy, 1010 mm2) using a multi-parametric MRI protocol, including diffusion, perfusion, and amide proton transfer (APT) imaging. Results showed that radiation necrosis consisted of a hypointense central zone and an iso-intense to slightly hyperintense peripheral zone on APT imaging, which reflected coagulative necrosis and reactive brain tissue, respectively. APT imaging can provide useful diagnostic information to assess radiation necrosis.

10:54 706.   CESTrho: A New Method for Studying Chemical Exchange at Intermediate Exchange Rates 
Feliks Kogan1,2, Hari Hariharan1, and Ravinder Reddy1
1CMROI, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States

Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites. In this study we developed a new method to measure proton exchange which combines CEST and T1ρ (CESTrho) magnetization preparation methods. We demonstrated that this new CESTrho sequence is more sensitive to proton exchange in the slow to intermediate exchange regimes, has a linear dependence on proton concentration and that the magnetization scheme can be customized to make it insensitive to changes in exchange rate. The increased sensitivity to chemical exchange and insensitivity to confounding factor that influence proton exchange rates make this sequence ideal for measurement of metabolites with exchangeable protons.

11:06 707.   Respiratory triggered Chemical Exchange Saturation Transfer MRI for pH Mapping in the Kidneys at 3T 
Jochen Keupp1, Edwin Heijman2, Sander Langereis2, Holger Grüll2, Dario L Longo3, Enzo Terreno3, and Silvio Aime3
1Philips Research Europe, Hamburg, Germany, 2Philips Research Europe, Eindhoven, Netherlands, 3Center for Molecular Imaging, University of Turino, Turino, Italy

A local MR pH measurement would be of high clinical interest, because several pathologies are associated with pH changes (i.e., tumors, renal diseases). CEST-MRI is promising, e.g. using Iopamidol as contrast agent, which exhibits two amide proton pools for a ratiometric pH measure independent of concentration. Existing CEST methodology was extended to anatomical regions affected by physiological motion by using a breathing triggered technique with continuous pulsed RF saturation during the wait time for the trigger event. Feasibility of motion compensated pH mapping in the kidneys of a rat could be demonstrated on a clinical 3T scanner.

11:18 708.   Water-metabolite hydroxyl proton exchange studied using spin-locking and chemical exchange saturation transfer approaches 
Tao Jin1, and Seong-Gi Kim1
1Neuroimaging laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States

The chemical exchange saturation transfer (CEST) approach, based on the hydroxyl-water proton exchange, can provide valuable information on the concentration of glycogen, glycosaminoglycans, and myo-inositol, etc. Compared to the well-studied amide-water proton exchange for which a long and low- power irradiation pulse is generally adopted, the faster hydroxyl-water proton exchange suggests that a higher irradiation pulse power would be necessary to optimize the chemical exchange (CE) contrast. Unfortunately, given the smaller chemical shift between the hydroxyl and water protons, this would also lead to a larger direct water saturation effect. Recently, we reported that a similar CE contrast can be obtained with a frequency offset-dependent spin-locking (SL) approach which minimizes the contamination of the direct water saturation effect. In this work, we evaluated the hydroxyl-water CE contrast with the CEST and SL approaches

11:30 709.   Detection of paraCEST Agents with Reduced MT Interference Using Frequency Labeled Exchange Transfer (FLEX) 
Chien-Yuan Lin1,2, Nirbhay N Yadav2,3, Joshua I Friedman4, S James Ratnakar1, A Dean Sherry1,5, and Peter C M van Zijl2,3
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 2F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States, 3Division of MR Research, Russell H. Morgan Dept. of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States, 4Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, Maryland, United States, 5University of Texas at Dallas, Dallas, Texas, United States

Paramagnetic chemical exchange saturation transfer (paraCEST) agents combine the benefit of a large chemical shift difference and a fast exchange rate for sensitive MRI detection. However, the in vivo detection of these agents is hampered by the need for high B1 fields to allow sufficiently fast saturation, causing interference of large magnetization transfer (MT) effects from semi-solid macromolecules. It is shown on phantoms that the use of frequency labeled exchange transfer (FLEX) allows detection of such rapidly exchanging agents and that interfering broad components such as MT effects can be removed using T2* filtering of the signal.

11:42 710.   Parallel RF Transmission based MRI Technique for Highly Sensitive Detection of Amide Proton Transfer in the Human Brain at 3T 
Jochen Keupp1, Christof Baltes2, Paul R Harvey2, and Johan van den Brink2
1Philips Research Europe, Hamburg, Germany, 2Philips Healthcare, Best, Netherlands

Amide proton transfer (APT)-MRI is expected to have clinical applications in oncology (enriched protein levels in tumors) and neurology (ischemic acidosis in stroke). While successful APT applications have been shown in the human brain, sensitivity was typically limited due to RF amplifier hardware specifications of the clinical systems. Herein, a novel scheme for prolonged RF saturation (greater than or equal to3 sec) is demonstrated, which is based on alternated parallel RF transmission into the body-coil and bears the potential for a twofold sensitivity gain. Sequence variants are assessed for optimal sensitivity, and feasibility of APT mapping in the human head is demonstrated.

11:54 711.   Examining the Accuracy of Dual Echo B0 Map for Field Inhomogeneity Correction with the Application of gagCEST in Articular Cartilage at 3T 
Wenbo Wei1, Guang Jia1, David C Flanigan2, Christopher C Kaeding2, Jinyuan Zhou3, Steffen Sammet1, Peter Arjan Wassenaar1, and Michael V Knopp1
1Wright Center of Innovation in Biomedical Imaging and Department of Radiology, The Ohio State University, Columbus, OH, United States, 2Department of Orthopedics, The Ohio State University, Columbus, OH, United States, 3Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

With a better B0 map acquisition in gagCEST imaging, an entire CEST spectrum is not necessary and total scan time can be reduced. In this study, B0 inhomogeneity correction using the dual echo B0 map with different Capital Greek DeltaTEs was performed to compare to the minimum point correction in gagCEST imaging of clinical knee patients. It shows that with proper Capital Greek DeltaTE B0 maps we are able to make reliable B0 inhomogeneity corrections to CEST spectra which enables gagCEST to be more feasible for clinical use.

12:06 712.   MRI Detection of Brain Glucose Uptake using Gluco-CEST 
Kai-Hsiang Chuang1, Cai Xian Yong2, Ying Min Wang2, George K Radda3, and Xavier Golay4
1MRI Group, Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore, 2MRI Group, Singapore Bioimaging Consortium, A*STAR, Singapore, 3Singapore Bioimaging Consortium, A*STAR, Singapore, 4Institute of Neurology, University College of London, United Kingdom

Radioactive isotopes of 2DG are being used routinely as surrogate measures of glucose uptake and metabolism in PET. Using chemical exchange saturation transfer (CEST), we demonstrate that 2DG can be detected by proton MRI. CEST signal demonstrates good correlation with 2DG concentrations in phantom. In vivo imaging shows 2DG uptake can be measured repeatedly in the rat brain similarly to the FDG PET but with higher image resolution. This provides a potential way of using MRI to study glucose uptake in vivo without the need of radio-isotopes.

12:18 713.   Dependence of CEST Effect from Amine Protons of Glutamate on pH  -permission withheld
Anup Singh1, Kejia Cai1, Mohammad Haris1, Joel H Greenberg2, Hari Hariharan1, and Ravinder Reddy1
1CMROI, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States

Dependence of CEST effect from amine protons of Glutamate (GluCEST) on pH is demonstrated using phantom and in-vivo rat data. While GluCEST has a non-linear dependence on pH from 1-8 it appear to vary linearly over a physiologically relevant pH changes between 6 and 7.4. In the ipsilateral side of middle cerebral artery occlusion (MCAO) model of stroke in rat brain, GluCEST is almost doubled at 4.5 hrs after occlusion compared to contralateral side.