Development and application of novel imaging and spectroscopic approaches to studying muscle function.
The objectives of my research program are to develop new magnetic resonance imaging (MRI) approaches to the study of skeletal muscle structure and function in vivo, to implement these methods in applied physiology and clinical studies, and to provide leadership in these areas to the scientific community. We have several lines of research to support these objectives:
Muscle Structure-Function Relationships
The first line of research in my lab is to understand the relationships among muscle architecture and the internal spatial patterns of strain development, perfusion, and metabolism during contraction. An important theme of our studies to date has been technique development. One of the new capabilities that we have developed combines structural and diffusion-tensor MRI techniques to study skeletal muscle architecture. We are able to form a highly spatially resolved description of the principal architectural features of a muscle, including its line of action, its boundaries, the position and orientation of its internal aponeurosis, and the internal arrangement of its fibers. This description forms a structural scaffold for the muscle, onto which we can overlay functional information and understand it relative to the anatomy. Recently, we have also developed a method for measuring the strain tensor in isometrically contracting skeletal muscle and have combined this approach with diffusion-tensor MRI to provide evidence for a significant deviation of the principal axis of fiber shortening from the principal fiber direction and for the development of shear strain during contraction. We have also implemented or developed methods for measuring perfusion and oxyhemoglobin saturation during contraction using MRI. In the future, we will advance our methods further and conduct a comprehensive study of muscle structure-function relationships in healthy muscle. We will contrast these findings with those from Becker muscular dystrophy patients.
MRI Detection of Muscle Microvascular Dysfunction
A second project in my lab is the study of the functional status of the skeletal muscle microcirculation and its alteration in obesity and type 2 diabetes mellitus. We have developed a simple, non-invasive test in which we use MRI to read out changes in blood volume and blood oxygenation following a brief isometric muscle contraction. The MRI methods themselves are quite standard, are easily optimized and implemented, and provide data that are simple to analyze. After providing an initial description of the physiological basis of this protocol, we examined its reproducibility and the sensitivity of its parameter estimates to image noise. We have implemented this protocol in a recently completed study of obese persons with and without type 2 diabetes mellitus. We found that the blood volume responses to muscle contraction are depressed to similar degrees in these groups, as compared to age-, gender-, and race-matched lean subjects.
Multi-parametric Characterization of Muscle Damage in the Inflammatory Myopathies
A third aspect of my research program is the development of improved MRI methods for detecting and quantifying muscle damage. My Co-Principal Investigator, Professor Jane Park, other colleagues at Vanderbilt, and I have for several years been developing MRI-based methods for characterizing tissue microstructure in healthy and diseased tissues; these include measurements of the diffusion-tensor, MRI relaxation time constants, tissue water compartmentalization, perfusion, and tissue macromolecular content. These methods, we believe, will provide for quantitative measures of myofibril disruption, membrane damage, inflammation, and reduced perfusion in damaged muscle. We have designed a series of studies, involving both animal and human models of muscle damage, to test our hypotheses. Ultimately, we intend to apply these methods in studies of patients with inflammatory myopathies.