We are submitting a request for $500,000 towards the purchase of a Magnex 11.74T/21 cm horizontal bore magnet for the development of an advanced magnetic resonance (MR) spectroscopy (MRS) and imaging (MRI) system for studying transgenic mice and rat models. The major aims of the research planned on the 11.74T system are to develop in vivo MRS and MRI measurements of metabolism and physiology, and apply these methods to understand the function of key gene products in transgenic mouse and rat models. The MR group at Yale, directed by Dr. Douglas L. Rothman who is the PI o this proposal, has been a leader in the development of MRS/MRI methods for studying metabolism in small animals and humans. The primary user group of the SIG consists of 8 NIH funded Yale investigators who will use the 11.74T to address fundamental questions relevant to human disease including the molecular regulation of muscle and liver carbohydrate and lipid metabolism in transgenic models of diabetes; the regulation of neurotransmitter glutamate and gamma-amino butyric acid release and recycling; the molecular mechanisms coupling glutamate neurotransmitter cycling to neuroenergetics; the neurophysiological basis of fMRI, and the functional neuroanatomy of mammalian sensory systems (e.g., whisker barrel cortex and olfactory bulb). The presence of an active human MR research program at the Magnetic Resonance Center (MRC) at Yale has facilitated the translation of these findings to clinical research studies in diabetes, epilepsy, neonatal hypoxia, obesity, and psychiatric disorders. These studies all have depended upon the development of quantitative high resolution MRS and MRI methods at the Yale MRC, made possible by state-of-the-art magnet technology. The importance of the further development of rodent MRS/MRI technology, for which the 11.74T system is critical, is emphasized by the recent approval of an award to Yale from the NIH to develop a transgenic Mouse Metabolic Phenotyping Center. This Center is a national resource which makes available to NIH funded investigators throughout the country with transgenic mouse models of diabetes the advanced MRS and MRI methods developed at Yale. This effort will make extensive use of the 11.74T system. We believe the long-standing tradition at Yale of innovation in MRS/MRI measurements and close interdisciplinary collaborations provide an ideal site for the development of an 11.74T in vivo MRS/MRI system and the application to transgenic mouse and other small animal models for understanding the molecular control of metabolism and physiology in health and disease.
