COBRE Pilot Project for Brandon Fornwalt: Center of Research in Obesity & Cardio

Grants and Contracts Details

Description

We will test our hypotheses with the following specific aims: 1) Quantify MRI-based measures of systolic and diastolic function in diet-induced obese mice compared to control mice serially throughout 16 weeks of feeding. Non-invasive quantification of myocardial function from cardiac MRI in mouse models has only recently become possible with improvements in the efficiency of image acquisition sequences and MRI field strengths (Figure 2).10 We propose to collaborate with a world leader in rodent cardiac MRI at the University of Virginia, Dr. Frederick Epstein, to quantify these advanced measures of cardiac function in mouse models of diet-induced obesity and control mice. The University of Kentucky recently purchased a state-of-the art Bruker 7 Tesla Clinscan MRI identical to the scanner that Dr. Epstein uses, thus facilitating a strong inter-institutional collaboration. 2) Determine the accuracy of T1-mapping MRI to quantify diffuse cardiac fibrosis compared to histology in mice who have received angiotensin infusion for 4 weeks. Recent advances in MRI technology have enabled acquisition of pre and post-contrast T1-relaxation time maps of the myocardium. Parameters derived from these T1 maps are thought to be related to levels of diffuse fibrosis in several clinical studies.11-13 However, this methodology has not been validated against histology in mouse models known to have diffuse fibrosis such as the proposed angiotensin infusion model. 3) Measure the accuracy of proton magnetic resonance spectroscopy to quantify intramyocardial lipid content compared to post-mortem mass spectrometry in leptin-deficient ob/ob and control mice. Magnetic resonance spectroscopy has been used in several clinical studies to quantify intracellular lipid content in cardiac myocytes.6, 14, 15 However, only one study has attempted to validate this technique in mice16, and the results are limited by the fact that the authors did not see a correlation between triglyceride content and lipid content measured with imaging. This is likely due to the fact that the authors only measured triglyceride content, while we propose to quantify the full spectrum of lipids using state-of-the-art mass spectrometry available at our institution
StatusFinished
Effective start/end date9/8/089/14/13

Funding

  • National Institute of General Medical Sciences

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