The overarching goal of this three year project is to develop and validate novel medical imaging methods to address the problem of obesity in elderly females. Aging and physical inactivity are associated with changes in body composition characterized by increases in fat mass and reductions in fat-free mass. Muscle-associated lipids, specifically intramuscular triglycerides (IMTG) may play larger role than appreciated with regard to muscle quality. Weight loss and exercise regimens effects on IMTG may alter myofiber orientation and density, and subsequently alter the effective muscle physiological cross-sectional area (PCSA) which is proportional to the maximum muscle force.
The specific aims of the proposed research are: (1) to establish the precision and sensitivity of Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) to quantify IMTG and histoarchitecture, defined as muscle quality, (2) to explore the relation of these muscle attributes to insulin action and muscle strength and physical function in elderly women differing in adiposity and habitual physical activity, and (3) after exercise training and weight loss.
The first aim will be met by employing a sophisticated phantom mimicking the hierarchical structure of the muscle. Towards aim (2-3), fifty elderly (65 80 y) females will be recruited and blocked on adiposity (normal weight vs. obese), and normal weight women will be further blocked on physical fitness (sedentary vs. physically active) and will be assessed for muscle associated lipids and histoarchitecture using a cross-sectional design. A parallel- arm study design will also be used with the obese women randomized to either a weight loss program induced by caloric restriction alone to elicit a reduction of 10% body weight or a weight stable exercise program for 6 months to explore the sensitivity of the MRI and MRS measures to histochemically known perturbations of muscle quality. It is anticipated that exercise will impact muscle quality more than body fatness (cross-sectional design) or weight loss (longitudinal study). Moreover, because lipids contained within or near muscle are speculated to reduce muscle quality both from a fuel and muscle strength perspective, quantitative measures of muscle quality afforded by MRI and MRS will be related to clinical measures of insulin resistance and muscle strength and performance. The further refinement and application of proton MRI and MRS to quantify IMTG impacts on muscle quality will aid the ultimate clinical translation of this project which is to elucidate mechanisms whereby weight loss or exercise improves muscle quality in obese women at risk for disability due to disordered body composition. Obesity in the elderly is linked to disability, reductions in independent living and quality of life. Lipids contained within or near muscle are speculated to reduce muscle quality both from a fuel and muscle strength perspective. Noninvasive and accurate medical imaging technologies (MRI) will be used to link the effect of nutrition and exercise on the structure and function of the thigh muscle in obese women at risk for disability due to disordered body composition.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL090455-03
Application #
7677986
Study Section
Special Emphasis Panel (ZHL1-CSR-J (S1))
Program Officer
Ershow, Abby
Project Start
2007-09-01
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2011-08-31
Support Year
3
Fiscal Year
2009
Total Cost
$220,152
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Hernando, D; Karampinos, D C; King, K F et al. (2011) Removal of olefinic fat chemical shift artifact in diffusion MRI. Magn Reson Med 65:692-701
Karampinos, Dimitrios C; King, Kevin F; Sutton, Bradley P et al. (2010) Intravoxel partially coherent motion technique: characterization of the anisotropy of skeletal muscle microvasculature. J Magn Reson Imaging 31:942-53
Karampinos, Dimitrios C; King, Kevin F; Sutton, Bradley P et al. (2009) Myofiber ellipticity as an explanation for transverse asymmetry of skeletal muscle diffusion MRI in vivo signal. Ann Biomed Eng 37:2532-46