MR is well suited for quantifying fat depots (e.g., visceral, subcutaneous, hepatic, muscular) and for helping to determine the role of genetic, environmental, and therapeutic factors on lipid accumulation, metabolism, and disease states. Colleagues and I will advance technologies for characterizing fat depots in rodents and apply them to important mouse models of obesity, including future studies of a unique set of 22 chromosome substitution strains to enable efficient discovery of obesity-related genes. Imaging technology developments will significantly increase the speed and robustness of image acquisition and analysis. We will develop radial Multi-Point Dixon (MPD) acquisitions to obtain a high resolution whole-body assessment of lipid levels. Ratio images will be created which eliminate any effect of receive coil inhomogeneity and which greatly facilitate accurate, semi-automated image analysis. MR spectroscopy of skeletal muscle will assess both saturated and unsaturated myocellular lipid levels. Because of the size of the data sets, we will develop image analysis/visualization software, including interactive, 3D segmentation, and volume measurements using a voxel mixture model that accounts for partial volume/mixed voxels. Our goal is a comprehensive imaging and """"""""electronic imaging report"""""""" in about 1.5 hours. Once technologies are firmly established, we will acquire baseline data on the two parent strains and dynamically characterize fat depots during weight gain/loss resulting from high and low fat diets. We will comprehensively evaluate the effects of diet and genetics on lipid accumulation and metabolism in the liver, muscle, and adipose tissue compartments and compare results to measures of insulin resistance so as to determine early biomarkers of metabolic disease. My intention is to create a paradigm for phenotyping mouse models of obesity and to dissect the role of genetics and perturbations such as dietary change, exercise, or drug therapy on fat depots.
Obesity is associated with many serious medical conditions, including high blood pressure, diabetes, heart disease, stroke, etc. We will develop robust and rapid non-invasive imaging technologies to study mouse models of obesity and to dissect the role of genetics and perturbations such as dietary change, exercise, or drug therapy on fat depots. The MRI techniques developed here can be readily translated to studies of human metabolic disease.
