A Specific Aims
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چکیده
Obesity is a growing epidemic in the United States, affecting multiple health outcomes in children, adolescents, and adults [2–5]. This increased risk includes metabolic disturbances such as glucose intolerance, insulin resistance, hyperlipidemia, diabetes mellitus, and cardiovascular and liver diseases [6–21]. Increasing data suggest that the link between obesity and poor health outcome is related to the buildup of fat in specific fat depots (e.g. visceral fat inside the abdominal cavity) and/or infiltration of fat into muscle, liver, and other organs. The assessment of fat distribution (and not simply total body fat) has become an important component of risk assessment, intervention, the evaluation of new therapeutic approaches, and basic research on the mechanisms explaining why obesity is related to poor health outcome. Magnetic resonance imaging (MRI) is potentially the most appropriate modality for such an assessment, because it (1) is inherently three-dimensional and therefore can resolve the relevant fat depots, organs, and tissues, (2) provides an extremely sensitive mechanism for separating water and fat, and (3) is completely noninvasive and involves no ionizing radiation, leading to indefinite repeatability and ultra-low risk for longitudinal studies in humans. MRI is becoming more frequently used in obesity research, but current protocols have several drawbacks including: (1) long and/or multiple breathholds required for 3D coverage, leading to patient discomfort and potential motion-related errors, (2) long scan-times and the high-cost of magnet time (∼$500 per hour), and (3) measurements are limited to adipose tissue volume or fat signal fraction rather than the potentially more relevant quantity of fat mass. In addition, in vivo MRI-measurement of total organ fat has never fully been validated against a gold standard such as chemical analysis. Our overall objective is therefore to develop, optimize, and fully validate a new MRI-based test that provides accurate regional quantification of abdominal fat in adipose tissue, critical organs, and skeletal muscle. The new test will consist of a single 3D scan of the entire abdomen with 3×4×4 mm3 spatial resolution, and an imaging time of 16 seconds (performed during a breathhold). Calibration scans will require two to three additional breathholds, and are expected to drastically improve the accuracy of computed fat mass. Validation will be performed in whole animals, using necropsy and chemical analysis as the gold standard. Our specific aims are:
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