The proposed research is a continuation and extension of basic and applied studies of optical properties and radiation transfer in tissues, and of associated selective tissue injury mechanisms inducible by photons. Realistic models of tissue optics have been developed and will be tested and applied to study optical dosimetry in a variety of organs of photomedical interest. A library of tissue optical properties over the ultraviolet, visible, and infrared spectral ranges will be compiled from the several experimental methods we have developed. The radiative transport theory underlying laser energy propagation will be incorporated in both finite-element and Monte Carlo models which allow treatment of heterogeneous tissues. New techniques for histochemical mapping of optical radiation and of thermal injury will be developed and used to corroborate theoretical models. This will lead to better understanding and manipulation of phototoxicity in vivo. New optical diagnostic techniques will also be developed including pulsed infrared radiometry for noninvasive measurement of absorption spectra in tissues and for detection of buried layers in tissues such as epithelial organs. An endoscopically useful system will be developed. Laser- induced fluorescence will be used to detect uptake of drugs in skin and tumors in tissue. Newly developed methods for producing monoclonal antibody-chromophore conjugates will be examined for localization of experimental tumor cell types in vivo in animal models. Photobiological injury and its repair will be studied for a unique optical pulse-dependent tissue effect known as selective photothermolysis, in which exquisitely localized damage is produced to cellular and subcellular targets. This interaction was described in our previous work and has already become a useful treatment for vascular malformations. Selective microvascular hemostasis will be studied and optimized. Selective photothermolysis of melanosomes, and studies of pigment cell damage mechanisms and repair in humans will be conducted. This pigment cell-specific effect leads to selective skin depigmentation, may be therapeutically useful in dermatology, and will be of basic interest in pigment cell biology.
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