Matthew Merritt, Ph.D.
Matthew Merritt, Ph.D., is developing new technologies for producing and using hyperpolarized compounds in MRI studies to measure the flux through metabolic pathways. He is also applying those technologies to explore normal metabolism, as well as the abnormal pathways in cancer and diabetes.
Hyperpolarization of nuclei to increase the signal available for magnetic resonance imaging (MRI) experiments is a relatively new branch of medical research. The advantage of this new technique is that metabolic reactions can be detected in real time, rather than seeing only the structure of organs within the body. Dr. Merritt is using hyperpolarized 13C pyruvate to study flux through the glycolytic pathway and the tricarboxylic (TCA) cycle.
In collaboration with Ralph DeBerardinis, M.D., Ph.D., he is using 13C pyruvate to analyze the glycolytic pathway in cell cultures of glioblastoma multiforme, the most common and aggressive brain cancer. These studies will enable an understanding of the aberrant metabolism of this cancer, and could also lead to a method to measure the efficacy of anti-cancer drugs in slowing cancer growth.
This same technique is also being used to study liver metabolism, and to assay models of liver dysfunction that mimic diabetes. In livers injected with hyperpolarized 13C pyruvate, the pyruvate carboxylase enzyme shunts the pyruvate into the gluconeogenesis pathway. This shunting is increased in a liver specific knockout of a single enzyme, changing the time dependence of the appearance of a variety of TCA cycle intermediates.
In summary, Dr. Merritt is developing new applications of hyperpolarization that aim to increase the applicability of MRI for understanding many metabolic disorders, instead of being limited only to diagnoses of structural anomalies.
In addition, Dr. Merritt and his colleagues are developing technologies to improve the hyperpolarization process. For example, a hyperpolarizer designed and constructed at the AIRC operates at a higher frequency than do commercially available machines, generating samples with higher hyperpolarization, increasing the sensitivity of MRI studies using hyperpolarized tracers. The new hyperpolarizer also produces larger amounts of tracer, enabling application of hyperpolarization MRI to larger research animals and to humans.
The researchers are also developing equipment for the new hyperpolarizer that will accelerate the hyperpolarizing process. The process of dynamic nuclear polarization (DNP) normally involves using microwave energy to transfer polarization to the electrons of the target molecule, which then spreads to the 13C nuclei. This process takes more than an hour to accomplish. However, the new methodology, which will enable hyperpolarization to be transferred first to protons and then to 13C, can reduce the hyperpolarization time to a few minutes. Quicker sample production will greatly enhance hyperpolarized MRI studies.
For publication information please view Dr. Merritt's faculty profile