The overall goals of this proposal are to develop and validate a novel magnetic resonance imaging (MRI) method for mapping tissue pH and phosphocreatine (PCr) and creatine (Cr) content and to apply this method to characterize exercise-induced changes in muscle metabolism in healthy and diseased states. The ability to assess such fundamental biophysical characteristics will have a broad range of clinical and preclinical applications. These include glycogen storage diseases, diabetes, and, most notably for this application, peripheral artery disease (PAD), a disease characterized by blood flow and intrinsic muscle mitochondrial deficits. The proposed methods for achieving this objective include a significant and novel reformulation of chemical exchange saturation transfer (CEST) imaging. There are inherent and critical technical obstacles to the widespread application of CEST methods and major limitations on their use in practice. CEST suffers from a lack of quantification and is highly susceptible to artifacts originating from static field inhomogeneities, lipid content, spectral overlap of multiple metabolites signals, and the inherently asymmetric background macromolecular resonance. Chemical exchange rotation transfer (CERT) is our proposed reformulation of CEST that overcomes the shortcomings of CEST. Furthermore, CERT can act as an exchange rate filter and can separate the contribution of Cr from that of other overlapping metabolites, such as PCr. We will 1) develop, optimize, and validate CERT imaging methods;2) quantify tissue changes in PCr and Cr content and pH in rat models of varied Cr content and exercise;and 3) quantify tissue changes in PCr, and Cr content and pH in human studies of exercise and peripheral artery disease.

Public Health Relevance

The goal of this proposal is to develop novel magnetic resonance imaging (MRI) methods for the biochemical characterization of muscle using the endogenous exchange of amide and amine protons with water to determine creatine and phosphocreatine content and pH. Such imaging methods will provide a new tool for studying disease progression, with particular relevance to studies of muscle pathology, most notably peripheral artery disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB017767-01
Application #
8615667
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Liu, Guoying
Project Start
2014-03-01
Project End
2018-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$352,194
Indirect Cost
$127,194
Name
Vanderbilt University Medical Center
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Zhang, Xiao-Yong; Wang, Feng; Li, Hua et al. (2017) Accuracy in the quantification of chemical exchange saturation transfer (CEST) and relayed nuclear Overhauser enhancement (rNOE) saturation transfer effects. NMR Biomed 30:
Zhang, Xiao-Yong; Wang, Feng; Jin, Tao et al. (2017) MR imaging of a novel NOE-mediated magnetization transfer with water in rat brain at 9.4?T. Magn Reson Med 78:588-597
Zu, Zhongliang; Louie, Elizabeth A; Lin, Eugene C et al. (2017) Chemical exchange rotation transfer imaging of intermediate-exchanging amines at 2 ppm. NMR Biomed 30:
Zu, Zhongliang; Li, Hua; Xu, Junzhong et al. (2017) Measurement of APT using a combined CERT-AREX approach with varying duty cycles. Magn Reson Imaging 42:22-31
Zhang, Xiao-Yong; Wang, Feng; Li, Hua et al. (2017) CEST imaging of fast exchanging amine pools with corrections for competing effects at 9.4 T. NMR Biomed 30:
Gore, John C; Zu, Zhongliang; Wang, Ping et al. (2017) ""Molecular"" MR imaging at high fields. Magn Reson Imaging 38:95-100
Li, Ke; Li, Hua; Zhang, Xiao-Yong et al. (2016) Influence of water compartmentation and heterogeneous relaxation on quantitative magnetization transfer imaging in rodent brain tumors. Magn Reson Med 76:635-44
Zhang, Xiao-Yong; Wang, Feng; Afzal, Aqeela et al. (2016) A new NOE-mediated MT signal at around -1.6ppm for detecting ischemic stroke in rat brain. Magn Reson Imaging 34:1100-6
Wang, Feng; Li, Ke; Mishra, Arabinda et al. (2016) Longitudinal assessment of spinal cord injuries in nonhuman primates with quantitative magnetization transfer. Magn Reson Med 75:1685-96
Li, Hua; Li, Ke; Zhang, Xiao-Yong et al. (2015) R1 correction in amide proton transfer imaging: indication of the influence of transcytolemmal water exchange on CEST measurements. NMR Biomed 28:1655-62

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