NONINVASIVE HIGH ENERGY PHOSPHATE IMAGING

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DESCRIPTION (Adapted from the applicant's abstract): Oxidative energy metabolism is essential for most cellular function including muscular contraction and ion transport. Phosphorus (31P) magnetic resonance spectroscopy (MRS) is unique in its ability to provide non-invasive access to key HEP metabolites such as adenosine triphosphate (ATP), the body's essential energy currency, and phosphocreatine (PCr), a key energy reserve. In the heart, clinical MRS shows reduced levels of PCr and ATP in infarction, and PCr/ATP ratios during ischemia. These and other MRS abnormalities seen in muscle disease, cancer, and the brain (e.g., stroke, some dementia), highlight the role of altered energy metabolism in common disease states, and its potential for evaluating therapeutic response. However, studies of HEPs access to deep-lying tissue, and the complexity of spectroscopic analysis. To address these critical problems, the investigators first demonstrated that the sensitivity of human HEP in the torso can be significantly increased by nuclear Overhauser enhancement (nOe) technique. Second, they separately showed that the use of (31)P phased-array coils can greatly increase sensitivity and access to PCr and ATP levels in the body. Third, to simplify MRS analysis, it has been demonstrated that HEP (PCr or PC and ATP) can be directly imaged in the body in the normoxic and ischemic conditions with chemical-selective (31)P MRI. The applicants now propose to combined phased-array with nOe technologies to provide critically important sensitivity gains of 3-fold and higher for (31)P studies of HEP in the body. They further propose that the combination of direct chemical-selective MRI of HEP will largely eliminate the analysis burden for MRS with phased-arrays. In addition, it is proposed that HEP imaging will further benefit from a priori spatial information acquired by routine proton MRI. The integration of these diverse new technologies presents new challenges requiring innovate solutions. Success in their integration will create a new biomedical research tool to non-invasively probe energy metabolism in human disease. Thus, the applicants propose to combine, for the first time, the sensitivity advantages provided by the physics technique of nOe with the engineering technique of phased arrays, chemical-selective MRI of medical imaging and new science analysis methods to create HEP imaging.