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High Energy Phosphate Metabolism Measurement by Phosphorus-31 Magnetic Resonance Fingerprinting

Wang, Charlie, Wang
http://rave.ohiolink.edu/etdc/view?acc_num=case1509364666422789

Abstract Details

2018, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Adenosine Triphosphate (ATP) serves as the universal currency of energy in cellular systems. Hydrolysis of ATP thermodynamically drives the majority of cellular processes fundamental to life. The existence of a fast and robust method to observe ATP and its reactions in vivo would have profound applications both in the clinical diagnosis of metabolic abnormalities, and in the evaluation of therapies. Phosphorus-31 (31P) spectroscopy is the only modality capable of non-invasive non-destructive in vivo detection of ATP and its reactions. However, 31P spectroscopy methods are often challenging to perform due to two reasons. First, the instruments have an inherently low sensitivity to the biological signal. Second, conventional 31P spectroscopy methods have emphasized mathematical tractability rather than optimal signal detection. Consequently, 31P spectroscopy methods require long experiment times, and this has precluded their use in many applications. In this thesis, a new acquisition paradigm, the Magnetic Resonance Fingerprinting (MRF) framework, was applied to 31P spectroscopy method design in order to shorten experiment times. By prioritizing signal detection over mathematical tractability, the methods designed in this thesis sought to overcome the limitations imposed by instrument sensitivity and shorten experiment times. Success in this goal may enable new applications. Three main projects are described in this thesis. First, the MRF framework based 31P-MRF method was used to obtain efficient and simultaneous quantification of T1 relaxation time and concentration of multiple metabolites. This method was tested in simulation and validated ex-vivo. Second, sensitivity to magnetization transfer (MT) effects between phosphocreatine (PCr) and ATP was added to the 31P-MRF method to measure the in vivo chemical exchange rate of creatine kinase enzyme. This new method, the CK-MRF method, was assessed in vivo rat hindlimb. Finally, the 31P-MRF method was further adapted to additionally incorporate measurements of ATP synthesis and hydrolysis. This third method, the MT-MRF method, was assessed in both simulation and in vivo experiments.
Dominique Durand, PhD (Committee Chair)
Chris Flask, PhD (Committee Member)
Mark Griswold, PhD (Committee Member)
Charles Hoppel, MD (Committee Member)
Nicole Seiberlich, PhD (Committee Member)
Xin Yu, ScD (Advisor)
140 p.
Biomedical Engineering; Medical Imaging
Phosphorus-31 Spectroscopy; Magnetization Transfer; Phosphate Metabolism; Magnetic Resonance Fingerprinting;

Recommended Citations

Citations

  • Wang, Wang, C. (2018). High Energy Phosphate Metabolism Measurement by Phosphorus-31 Magnetic Resonance Fingerprinting [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1509364666422789

    APA Style (7th edition)

  • Wang, Wang, Charlie. High Energy Phosphate Metabolism Measurement by Phosphorus-31 Magnetic Resonance Fingerprinting. 2018. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1509364666422789.

    MLA Style (8th edition)

  • Wang, Wang, Charlie. "High Energy Phosphate Metabolism Measurement by Phosphorus-31 Magnetic Resonance Fingerprinting." Doctoral dissertation, Case Western Reserve University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1509364666422789

    Chicago Manual of Style (17th edition)

case1509364666422789
411
© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.