This proposal requests funding to support a new, state-of-the-art, high-resolution 400- MHz magnetic resonance spectrometer and imager for studying metabolic pathways using hyperpolarized carbon and nitrogen technology. The proposed system will initially be used by thirteen NIH-funded projects and led by well-established investigators at the University of Pennsylvania, Children Hospital of Philadelphia, and the Lankenau Institute for Medical Research. At present, the proposed resource is the only feasible way to pursue further pre-clinical cell culture and animal testing of hyperpolarized carbon-13 technology. An existing NMR spectrometer at our facility is more than 25 years old, and has recently become unreliable in addition to long-standing difficulties with scheduling and availability. Incorporation of a new system with modern shielding into a dedicated hyperpolarized core will allow favorable positioning of the equipment near a DNP polarizer, and the permanent incorporation of required ancillary equipment. This will make it possible for a number of investigators to use hyperpolarized carbon-13 technology in variety of different research projects. This instrument is necessary for continued expansion of hyperpolarization studies. It will be used primarily for in vivo metabolic studies with hyperpolarized contrast agents, although several perfused organ, perfused cell mass are proposed, as is one project which makes use of DNP signal enhancement for NMR quantification of extracts. The core will be initially used by three departments at the University of Pennsylvania, two departments at the Children Hospital of Philadelphia, and the Lankenau Institute for Medical Research. We expect this number to grow substantially as the resource becomes more widely known and established. The system will be available as a shared resource to investigators at the University of Pennsylvania. Departments that will benefit include: Radiology, Pulmonary, Medicine, Biophysics and Bioengineering. This is supported by currently active collaborations between the investigators from these departments. We expect that such a system will significantly enhance investigational and collaborative research related to the emerging and powerful technology of hyperpolarized carbon-13 and its application in metabolic imaging and spectroscopy. If funded, this proposal, along with the other identified commitments, will provide the resources to make a comprehensive metabolic resource available to the investigative research programs outlined in the descriptions of individual projects. The system will be placed at and maintained by the facilities of the Department of Radiology at the University of Pennsylvania and will be managed and directed by an Internal Advisory Committee composed of the PI, co-investigators, and the principal users.
