Tao Wang1,2, Xiao-Hong Zhu1, Huan Li1,3, Yi Zhang1, Wei Zhu1,2, Hannes M Wiesner1, Wei Chen1. 1. Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA. 2. Department of Medical Physics, Radiation Oncology, University of Minnesota, Minneapolis, Minnesota, USA. 3. Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Abstract
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.
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.
Authors: Henk M De Feyter; Kevin L Behar; Zachary A Corbin; Robert K Fulbright; Peter B Brown; Scott McIntyre; Terence W Nixon; Douglas L Rothman; Robin A de Graaf Journal: Sci Adv Date: 2018-08-22 Impact factor: 14.136