Noninvasive assessment of myocardial energy metabolism and dynamics using in vivo deuterium MRS imaging

• Published in: Magnetic resonance in medicine 2021-12, Vol.86 (6), p.2899-2909
• Main Authors: Wang, Tao, Zhu, Xiao‐Hong, Li, Huan, Zhang, Yi, Zhu, Wei, Wiesner, Hannes M., Chen, Wei
• Format: Article
• Language: English
• Subjects: Accumulation; acetate; Acetic acid; Animals; Biomarkers; Deuteration; Deuterium; Energy Metabolism; Glucose; Glucose - metabolism; Glutamine; Humans; Imaging; In vivo deuterium MRS imaging; Magnetic Resonance Spectroscopy; Metabolic rate; Metabolism; Metabolites; myocardial energy metabolism; myocardial TCA cycle activity; Myocardium; Myocardium - metabolism; Perfusion; Pilot Projects; Rats; Substrate preferences; Substrates; Tricarboxylic acid cycle; Turnover rate
• ISSN: 0740-3194; 1522-2594
• DOI: 10.1002/mrm.28914

Purpose The assessment of cellular energy metabolism is crucial for understanding myocardial physiopathology. Here, we conducted a pilot study to develop an alternative imaging approach for the assessment of myocardial energy metabolism. Methods We developed a deuterium MRSI method to noninvasively monitor the accumulation of deuterated downstream metabolites and deuterated water in rat hearts infused with deuterated glucose or acetate substrate on a 16.4 Tesla animal scanner. Results We found that the deuterated water accumulation rate and isotopic turnover rate of deuterated glutamate/glutamine via the tricarboxylic acid cycle and exchange in rat hearts were much higher when infused with acetate compared to that with glucose, demonstrating the myocardium substrate preference for acetate over glucose. Conclusion We demonstrated the feasibility of deuterium MRSI for noninvasive imaging and assessment of myocardial energy metabolism in vivo. Although the strong signal and large dynamics of myocardial deuterated water may provide a sensitive imaging biomarker, quantifying the metabolic rates still poses a challenge due to the confounding effects of blood recirculation, perfusion, and multiple deuterated water production pathways. In contrast, the deuterated glutamate/glutamine signal and change should directly reflect the metabolic activity of the myocardial tricarboxylic acid cycle, which can be used to study the metabolic shift in substance preference between acetate and glucose in the diseased state. Deuterium MRSI is noninvasive and robust and may have the potential to assess myocardial energy metabolism in human patients.