The urgent need for a fast, safe, economical, noninvasive approach to global and localized brain studies of the desaturation of hemoglobin together with the possibility of early detection of hemorrhage, aneurysm and stroke volumes can be met by research on spectroscopy and imaging with three novel technologies. The scattering of light by the skin, skull and brain tissue requires these recently developed technologies: time domain (TD), frequency domain (FD) spectroscopy and phased array (PA) imaging. Multiwave TD/FD affords a global or hemispheric quantitative determination of hemoglobin saturation and blood volume already demonstrated in human brain to be highly precise measure of clinical utility. This is also the case in early detection of brain bleeds, hematoma, hemorrhages, etc. in emergency health care. The theoretical basis for these methods is the diffusion equation. The point-by-point fitting of experimental data deconvolutes the absorption (mu a) and the scattering (mus') coefficients for TD. A novel """"""""substitution' method allows the precise determination of mu a and mu s"""""""" for small excised portions of brain tissue identifying the eventual imaging contrast obtainable for gray/white matter in the brain. Using these values of brain mu a and mu s' a """"""""brain slab"""""""" model provides a definitive evaluation of the ability of TD and FD to determine the oxygen saturation of hemoglobin in localized volume (o.5 gram) and to determine its position in two dimensions. A hundred-fold increase in sensitivity is obtained using Phased Array (PA), the recently discovered low frequency, long wave (10 cm) diffusive waves of light in highly scattering media (such as human brain). Interference between such diffusive waves arising from two light sources that are coded in phase gives highly sensitive amplitude nulls or phase transitions. Positional detection to less than 1 mm obtained in volumes of localized absorbers of less than 0.1 gram. Subnanomole amounts of a model contrast agent or hemoglobin at hematocrits of a few percent can be detected in a brain slab model. TD and FD systems optimally quantitate global and localized hemoglobin saturations and blood concentrations. The phased array system (PA) localizes absorption and extremely small scattering and absorption anomalies in brain tissue due to bleeding, aneurysm, stroke volume, on the one hand, and diseases which alter the scattering or the organelle content of brain tissue, for example, Alzheimers disease and white matter disease, on the other.
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