Three-Dimensional Tissue Dynamics Imaging

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1263753NolteThe proposed research will develop a multimodal imaging system that integrates TDI with simultaneous confocal and low-coherence backscatter imaging. The molecular specificity of the confocal channel, and the cellular and nuclear morphology changes from the backscatter channel, will serve to validate TDI and identify the biological mechanisms that correspond to the features observed in drug-response TDS spectrograms. They will use the multichannel system to study two well-known classes of compounds: mitochondrial toxins and Raf kinase inhibitors. TDI then will be applied to study apoptosis/necrosis, mitosis/cytokinesis and biochemical/biomechanical oscillations. These processes are important markers for drugefficacy and present strong physiological responses that make them ideally suited to study withdynamic imaging. This research will establish the types of intracellular motion that are detected by tissue dynamic imaging, the sensitivity, and the specificity to different types of mechanism of drug action. TDI will be able to track physiological responses of tissue, enabling discovery of new dynamic processes and enhancing knowledge of tissue-scale biodynamics. The successful completion of the proposed research will lay the foundation for tissue dynamics imaging to become a unique imaging tool with a broad array of future biomedical applications. These potential applications include the discovery of new drug candidates with lower side effects and lower costs to consumers, the selection of cancer chemotherapy specifically tuned to the patient to improve cancer remission and patient quality of life, and improvement in the success rate of in vitro fertilization to reduce health-care costs and remove medical complications of multiple births.This award is co-funded by the Division of Biological Infrastructure (DBI) through the Instrument Development for Biological Research (IDBR) program, and by the Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET).