Applications Of Deuterium Magnetic Resonance Spectroscopy Imaging In Assessing Cellular Energy Metabolism In Vivo

Abstract

The in vivo assessment and imaging of cellular metabolism and metabolic changes is crucial for understanding neurodegenerative diseases and brain tumors, as disruptions in brain glucose metabolism have broader health impacts. Deuterium Magnetic Resonance Spectroscopy Imaging (DMRSI) with administration of a non-radioactive deuterium (2H) isotope labeled substrate, has emerged as a promising imaging technique in this field. It offers advantages over traditional methods like robustness, higher signal-to-noise ratio and imaging resolution. Furthermore, DMRSI enables detailed study of cellular energy metabolism in vivo, particularly at ultrahigh magnetic field (UHF), and it potentially allows simultaneous measurement and imaging of the cerebral metabolic rates of glucose consumption, the tricarboxylic acid (TCA) cycle, and lactate production in the brain. My Ph.D. thesis work aims to explore and demonstrate the new utilities of DMRSI in assessing glucose energy metabolism in vivo at UHF. First, I apply the advanced high-resolution DMRSI approaches to investigate the cellular energy metabolism using the rat brain tumor model at 16.4 Tesla and assess the “Warburg Effect” associated with cancer biology and intra-tumor heterogeneity. Secondly, I explore the DMRSI capability into a more humanized preclinical mice brain model to further push the spatial-temporal resolution of DMRSI and demonstrate the unprecedent imaging quality achieved in small mice brains at UHF. Finally, to further demonstrate DMRSI versatility, I use DMRSI for the first time to examine myocardial metabolisms in rats to confirm acetate being the preferred substrate in myocardium energy. Overall, the DMRSI technology advancement and findings from my work show great promise and potential for imaging and studying the energy metabolism using a variety of preclinical models under various physiopathology conditions.