The fundamental role of abnormal intermediary metabolism in disease is well-known. Excess glucose uptake by many cancers, abnormal mitochondrial function in dysfunctional but viable myocardium, and abnormal lipid and glucose production from the liver in type 2 diabetes have long been studied in various experimental systems and humans. 13C NMR is overwhelmingly the best method to probe metabolic networks in vivo but clinical applications are severely hampered by the poor sensitivity of 13C NMR arising from the low polarization of 13C in conventional MRI. This proposal seeks to establish a facility for clinical research in 13C MRI based on dissolution dynamic nuclear polarization methods (hyperpolarization), a process that enhances the 13C signal by 10,000x - 60,000x and enables imaging of 13C in human patients. We propose to purchase a SpinLab, an instrument designed for high-level polarization of 13C that incorporates a quality-control device for human studies. The SpinLab will be placed adjacent to a newly-installed, research-dedicated 3T MRI scanner with multiple 13C coils. This program will leverage extraordinary institutional support for space, equipment and personnel. The UT Southwestern environment is ideal for developing this technology because, in addition to relevant research infrastructure, the SpinLab will be adjacent to a clinical environment. Experts in synthetic chemistry, MR physics, engineering, physiology and radiology will have access. This diverse user group, including the physicians, shares one commonality in having a long track record of metabolic studies using conventional 13C NMR. The local expertise for managing and operating this system is outstanding. An Internal Advisory Committee will meet monthly to provide oversight, establish priorities and assure balanced access. Although imaging hyperpolarized nuclei is technically challenging, the techniques are available and the biochemical principles required to interpret the images are well-understood. There are no known insurmountable barriers in developing this technology for imaging specific enzyme-catalyzed reactions in patients.
