DESCRIPTION (Verbatim from the Applicant?s Abstract): Tissue-to-tissue variations in longitudinal (R1) and transverse (R2) relaxation rates are the main source of contrast in clinical NMR images, and are also altered by such physiological conditions as exercise. The biological influences on R1 and R2 are not well understood, however. Therefore, the proposed research project will address the question of why R1, R2, and other NMR parameters change during exercise in vivo, in order to provide a clear scientific rationale for studies of muscle recruitment and muscle pathology. To do so, we will: 1) test the hypotheses that intracellular acidification throughout the physiological range will decrease R1 and R2,I and that these changes are mediated through changes in magnetization transfer rates; 2) determine how the structural geometry of muscle changes during exercise, and test the hypothesis that alterations in water compartmentation or the permeability of the boundaries are related to exercise-induced changes in water diffusion, R1, R2,I and R2,E; 3) measure membrane permeability in resting muscle and determine how it changes as a function of exercise; and (4) test the hypothesis that blood volume and blood flow changes affect the in vivo NMR relaxation behavior of muscle water, and determine if these effects are different depending on whether the muscle is at rest or is exercising. These studies may also provide new insights into relaxation in vivo in other tissues, and the changes that occur in clinical imaging of pathopphysiological conditions. Novel information concerning the physiology of exercising muscle will also be generated.