Magnetic Resonance Spectroscopy (MRS) provides a powerful tool to interrogate various aspects to tissue metabolism. In particular, phosphorus-31 (31P) magnetization transfer spectroscopy (MT-MRS) has long been proposed as a means of measuring ATP synthesis rate in vivo. However, current 31P MT-MRS methods require prohibitively long data acquisition time to accurately quantify ATP synthesis rate. On the other hand, recent development of magnetic resonance fingerprinting (MRF) method provides a completely new framework of data acquisition that allows simultaneous measurement of several tissue properties, including relaxation times, at drastically reduced acquisition time. The measurement of chemical exchange rate in MT-MRS involves the measurement of the apparent relaxation time (T1app), i.e., the chemical exchange modified T1 relaxation, which is highly analogous to the measurement of T1 in proton imaging. Therefore, the overall objective of this proposal is to develop and validate novel 31P MT-MRF technique for fast and accurate quantification of ATP synthesis rate in hearts. This project has two specific aims.
Aim 1 has three parts: 1) designing and evaluating 31P MT-MRF methods by computer simulation; 2) implementing and optimizing the 31P MT-MRF methods in phantom experiments, and 3) validating the 31P MT-MRF methods against established 31P MT-MRS methods in perfused hearts under varying workload.
In Aim 2, the feasibility of performing spatially resolved measurement of chemical exchange rate by 31P MT-MRF will be investigated. A compressed sensing spiral 31P chemical shift imaging (CSI) sequence will be developed that will lead to 92-fold acceleration over the Cartesian CSI method. The 31P MT-MRF CSI method will be validated in rat model of ischemia/reperfusion injury in skeletal muscle. Methods developed in this pre-clinical project will lay the foundation for the development of clinical methods that can be applied to evaluating metabolic function in a variety of metabolic diseases such as diabetes and obesity.

Public Health Relevance

The objective of this proposal is to develop a fast in vivo magnetic resonance spectroscopy/imaging method for sensitive measurement of tissue metabolism and mitochondrial response to ischemia-reperfusion injury. The method developed in this project will pave the way for clinical investigation of mitochondrial metabolism, as well a assessing disease progression and therapeutic effects of a spectrum of metabolic diseases such as diabetes and obesity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL126215-02
Application #
9105418
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Danthi, Narasimhan
Project Start
2015-07-15
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Gu, Yuning; Wang, Charlie Y; Anderson, Christian E et al. (2018) Fast magnetic resonance fingerprinting for dynamic contrast-enhanced studies in mice. Magn Reson Med 80:2681-2690
Ma, Chao; Clifford, Bryan; Liu, Yuchi et al. (2017) High-resolution dynamic 31 P-MRSI using a low-rank tensor model. Magn Reson Med 78:419-428
Liu, Yuchi; Gu, Yuning; Yu, Xin (2017) Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review. Quant Imaging Med Surg 7:707-726
Liu, Yuchi; Mei, Xunbai; Li, Jielei et al. (2016) Mitochondrial function assessed by 31P MRS and BOLD MRI in non-obese type 2 diabetic rats. Physiol Rep 4: