These investigations are devoted to the development of noninvasive methods of accessing tissue structure and function. Two general techniques are being developed: nuclear magnetic resonance (NMR) and optical spectroscopy/imaging. Over the last year we have made the following developments in NMR technology: (1) We have further developed the theory and application of magnetization transfer contrast (MTC) to the study of biological tissues. This approach permits the imaging of the interaction rate between water and macromolecules in the body resulting in a unique form of high resolution image contrast and tissue characterization. The quantitative aspects of this approach, defining its frequency and power dependence, were established out-lining the methods of obtaining quantitative rate constant maps in vivo. (2) 3-H NMR studies have revealed that the interaction of water with macromolecules, the dominant source of contrast in tissues, is due to spin diffusion between the water and the macromolecules. (3) The molecular basis with macromolecules was evaluated which of the dipoler interaction of water demonstrated a unique role for hydroxyl groups in lipid bilayers. (4) The first human images using MTC were collected by adding a second radiofrequency channel to a standard clinical scanner. These images were 3-dimensional images of the knee revealing excellent soft tissue contrast. (5) A quantitative relationship between 3-fluorsorbitol production from 3-fluorodeoxyglucose and aldose reductase activity was established in the isolated lens of the eye, suggesting that this approach is a viable method of monitoring aldose reductase activity in vivo. Using optical spectroscopy the following advancements were made: (1)The effects of inner filters on the optical behavior of calcium indicating dyes and NAD(P)H fluorescence in the intact heart were defined and methods developed to correct for these serious artifacts. (2) Methods were further developed for the monitoring of tissue oxygenation in vivo using optical spectroscopy in the 500 to 650 nm range.
