The research proposal objective is to develop dynamic nuclear polarization (DNP) techniques for MR studies of heart. DNP enhances nuclear spin polarization and thus MR signal 10,000-fold, enabling one to track the metabolism of cellular substrates in vivo using 13C MR spectroscopy. Initial work will involve development of hyperpolarizer protocols that will allow rapid administration of hyperpolarized tracer to rat hearts. Monitoring of in vivo Krebs cycle reactions will be verified through comparison with steady state metabolic data, and using ex vivo 13C MR spectroscopy. Baseline metabolite monitoring will be established in normal heart in vivo, and kinetic models will be developed to demonstrate the unprecedented temporal resolution of DNP-MR data. Models of heart disease will be investigated to determine kinetic differences in substrate uptake and enzymatic transoformation, as compared to the control healthy heart. This information will link cellular metabolism with whole heart function. In the long term, it is anticipated that differences in cellular metabolism of heart tissue may be examined as a novel clinical method to enable early diagnosis of heart disease. This proposal will be investigating DNP-MR, a novel non-invasive method with potential to monitor in vivo metabolism in real time. The method will be established as a tool in basic physiology research that can help explain the link between cellular metabolism and whole organ disease. In the long term, DNP-MR may be implemented as an innovative clinical method to aid early diagnosis of a range of metabolic diseases.
