Measuring metobolic flux with magnetic resonance spectroscopy and imaging
The Merritt lab focuses on developing methods for assessing metabolic turnover and energy metabolism, and applying these new technologies to diverse pathophysiologies including heart failure, cancer, and diabetes mellitus. New technology based on magnetic resonance imaging (MRI) now allows real-time in vivo metabolic imaging that is sensitive to energy availability and substrate selection. Dynamic nuclear polarization (DNP) can amplify signal from MRI experiments by a factor of 40,000 or greater. The left panel of the figure shows the metabolic products of pyruvate metabolism with 1 second time resolution. This 4 orders of magnitude advance in MR sensitivity allows kinetic investigations in living systems. The center panel illustrate absolute flux measurements in and out of the tricarboxylic acid (TCA) cycle in two types of cancer cells. The top diagram details flux in a human glioblastoma cell line, which has an oxidative phenotype, compared to a hepatocellular carcinoma cell line, which has an anaplerotic phenotype. These differing metabolic phenotypes suggest alternate pathways are appropriate for targeted treatment. The 13C MR spectra in the right panel shows the differences in steady state metabolism that can be detected after administration of carbon-13 labeled substrates. My lab clearly has a strong technological bent, but the ultimate target always remains the understanding energy metabolism.
