High Field NMR System for Metabolic Imaging of Human Disease

University Of California, San Francisco, San Francisco CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): This is a proposal to obtain a 600 MHz Varian wide bore NMR spectrometer with full micro-imaging and high resolution magic angle spinning (HR-MAS) spectroscopy capabilities. This spectrometer will provide a -17% increase in resolution and ~42% increase in sensitivity over our current 500 MHz Varian system, with even higher S/N expected due to improved hardware components that produce less noise. The spectrometer will enable 2D HR-MAS studies of very small (~3-10mg) biopsy tissues to be performed quickly enough to preserve the metabolic, pathologic, and genetic integrity of the tissues for subsequent analysis. The proposed 600 MHz spectrometer will also be critical for the application of MR imaging and spectroscopy to pre-clinical mouse models of human disease and will be uniquely coupled to a Dynamic Nuclear Polarization (DNP) system that can provide a 40,000-fold increase in S/N of NMR signals from 13C labeled metabolites. The spectrometer will be utilized by a multidisciplinary network of investigators, who are leaders in the fields of biomedical magnetic resonance imaging and spectroscopy, to significantly advance our understanding of the relationships between metabolism and the pathologic and genetic origins of human disease. The requested spectrometer will directly benefit four large NIH-funded MR imaging programs, several smaller funded projects, and two training programs. The specific programs included are: HR-MAS studies of prostate, breast, and brain cancer tissues, before and after therapy; HR-MAS studies of tissues and amniotic fluids to evaluate breast density, fatty liver disease, intervertebral disc degeneration, and fetal lung maturity; micro-imaging of athymic mice and transgenic mouse models of human disease; and DNP studies of hyperpolarized 13C labeled substrates in cells and mice to characterize metabolic pathways in prostate and brain tumors and other diseases. The impact of these studies on public health will be the identification of novel imaging biomarkers and the development of high field imaging techniques that can be exploited clinically to improve the detection of human disease and the evaluation of therapeutic response. Finally, the spectrometer will be used to train several graduate students, post-doctoral fellows, and basic and clinical scientists for careers in high field MR imaging and spectroscopy. [unreadable] [unreadable] [unreadable]