Karin Shmueli¹, Stephen J Dodd², Christian Wunder³, and Jeff H Duyn^1
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 (f_x) have been measured in brain tissue. Cerebrosides are proposed to contribute because they are more abundant in WM than GM. We measured f_x 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. f_x 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 f_x. These findings should aid in interpreting MR frequency contrast.

Silun Wang¹, Erik Tryggestad², Michael Armour², Eric Ford², Tingting Zhou¹, Kun Yan¹, Zhibo Wen¹, Peter C.M. van Zijl^1,3, and Jinyuan Zhou^1,3
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.

Feliks Kogan^1,2, Hari Hariharan¹, and Ravinder Reddy^1
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.

Jochen Keupp¹, Edwin Heijman², Sander Langereis², Holger Grüll², Dario L Longo³, Enzo Terreno³, and Silvio Aime^3
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.

Tao Jin¹, and Seong-Gi Kim^1
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

Chien-Yuan Lin^1,2, Nirbhay N Yadav^2,3, Joshua I Friedman⁴, S James Ratnakar¹, A Dean Sherry^1,5, and Peter C M van Zijl^2,3
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.

Jochen Keupp¹, Christof Baltes², Paul R Harvey², and Johan van den Brink^2
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 (3 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.

Wenbo Wei¹, Guang Jia¹, David C Flanigan², Christopher C Kaeding², Jinyuan Zhou³, Steffen Sammet¹, Peter Arjan Wassenaar¹, and Michael V Knopp^1
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 TEs was performed to compare to the minimum point correction in gagCEST imaging of clinical knee patients. It shows that with proper TE B₀ maps we are able to make reliable B₀ inhomogeneity corrections to CEST spectra which enables gagCEST to be more feasible for clinical use.

Kai-Hsiang Chuang¹, Cai Xian Yong², Ying Min Wang², George K Radda³, and Xavier Golay^4
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.

Anup Singh¹, Kejia Cai¹, Mohammad Haris¹, Joel H Greenberg², Hari Hariharan¹, and Ravinder Reddy^1
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.