The novel technology of photon diffusion or migration in tissue (diffusometry) permits the detection and localization of a variety of parameters that permit a characterization of the structural and functional properties of normal host and embedded tumor tissue. The two parameters, apparent scattering coefficient (mus', cm-1) and absorption coefficient (mua, cm-1) are determined from photon kinetics in tissues in response to a light pulse (time resolved spectroscopy, TRS). Their ratio is determined by high frequency sinusoidal oscillation of the light intensity and phase sensitive detection of the signal (phase modulation spectroscopy, PMS). The location of the absorber is triangulated by in- phase and anti-phase laser diode arrays (phased arrays) based upon photon density interference (PDI) that afford angular accuracies of < 0.5o in 100 microliter volumes of 1 nmole absorber. Saturation of hemoglobin with oxygen (Y) is measured by the ratio of mua's at two appropriate wavelengths by TRS or the phase shifts at two wavelengths by PMS. The research program proposes to quantify mua and mus' of small samples of organelles, cells and biopsy/autopsy tissue samples that cover the expected range of parameters of host tissue and tumors. The research has three stages:
Aim 1) Homogeneous scattering/absorber systems at multiple input/output positions, mua, mus', mus'/mua. Lipid vesicles, intracellular organelles (mitochondria etc. endoplasmic reticulum) and cells (ascites tumors and cytochrome alphaalpha3 free and cytochrome alphaalpha3 sufficient yeast (petit and wild) are used with varying amounts of hemoglobin or carboycyanine dyes as absorbers;
Aim 2) The sensitivity in the detection of the differences of saturation of a localized blood volume with respect to a hemoglobin containing background will be evaluated by TRS, PMS, and PDI;
and Aim 3) Heterogeneous systems with single and multiple localized absorbers (scatterers, fluorochromes) of various volumes and locations. In-phased and anti-phased arrays causing photon density interference (PDI) will be tested for precision of angular position as a function of sample volume, mua, mus', etc. Thus, the detectable fraction of the optical field containing altered mus' and mua and fluorescence will be measured in model systems and will afford a solid basis for prediction of resolution and precision of human tumor spectroscopy is to be obtained.
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