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Phenotyping Rodent Models of Obesity Using Magnetic Resonance Imaging
Johnson, David Herbert

2010, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.

The emergence of dedicated, small animal imaging systems provides an excellent opportunity to study obesity using the rat and mouse models which will be critical to increasing our basic knowledge as well as deriving new treatments. MRI 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. Assessment of lipid depots is important because of the linkage of visceral and ectopic depots to insulin resistance, vascular disease, etc.

The importance of making reproducible imaging measurements can never be underestimated when conducting a study of many animals, and we demonstrated that ratio imaging enables reliable quantification even on a human clinical 1.5T MRI scanner. Scan-rescan variability and intra-operator variability were each reduced to a 2% coefficient of variation or less when the semi-automatic ratio image analysis was used. Receiver coil signal intensity inhomogeneity of over 200% across the field of view was flattened to less than 3% variation by ratio imaging. Using the SHR/SHROB rat model of dietary and genetic obesity, we found a novel image phenotype which showed that visceral adipose tissue depots are increased in both genetic and dietary obesity, but subcutaneous adipose tissue is uniquely linked to dietary obesity, at least in this model.

A method for robust fat-water reconstruction was developed on a small animal, high field scanner, where field inhomogeneity is far worse than on a clinical scanner. Severe field inhomogeneity was corrected by adapting the Iterative Decomposition and Echo Asymmetry with Least squares estimation (IDEAL) to the high field scanner. IDEAL reconstruction time was reduced by 50% when a graphics card was used in calculating a novel, vectorized form of the IDEAL equations. The reconstruction was also improved by applying a priori constraints to the linear extrapolation and fitting of the field inhomogeneity parameter, which removed error propagation across the image.

MRI phenotypes were identified and validated on the high field scanner using an important, well-established mouse model of dietary obesity. C57BL/6J mice on high and low fat diets were imaged using the new IDEAL technique, and the semi-automatic ratio image analysis was used to show significant differences in visceral and subcutaneous adipose tissue volumes. High fat diet mice had significantly higher concentrations of liver lipids than the low fat diet mice whether measured by IDEAL (P=0.002) or by a chemical assay (P<0.001). In contrast to IDEAL, CHESS measurements failed to detect reliable differences in either tissue volumes or liver fat content, demonstrating the clear superiority of the IDEAL technique for phenotyping mice on the high field scanner.

David Wilson, PhD (Committee Chair)
Christopher Flask, PhD (Committee Member)
Xin Yu, PhD (Committee Member)
Nadeau Joseph, PhD (Committee Member)
113 p.

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Johnson, D. (2010). Phenotyping Rodent Models of Obesity Using Magnetic Resonance Imaging. (Electronic Thesis or Dissertation). Retrieved from

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Johnson, David. "Phenotyping Rodent Models of Obesity Using Magnetic Resonance Imaging." Electronic Thesis or Dissertation. Case Western Reserve University, 2010. OhioLINK Electronic Theses and Dissertations Center. 23 Oct 2017.

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Johnson, David "Phenotyping Rodent Models of Obesity Using Magnetic Resonance Imaging." Electronic Thesis or Dissertation. Case Western Reserve University, 2010.


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