This application emphasizes two complementary approaches directed at increasing the sensitivity and specificity of breast tumor detection: 1) to use optical contrast agents which occupy the vascular and extravascular volumes of the tumor to enhance the tumor contrast with respect to the normal tissue background; and 2) to exploit the remarkable sensitivity and specificity of small object detection achievable by amplitude cancellation (phased array) diffusion wave optical systems. The contrast agent of particular interest is indocyanine green, an FDA- approved dye for studying the retina, the liver, the heart and the brain and here used for optical detection of specific tumor characteristics. The method also can employ multiwavelength contrast agent detection to enhance the specificity/sensitivity and to afford detection of blood occupied vascular volume and blood deoxygenation. The work proposes extensive studies of appropriate models for the breast tumor and will focus on in vitro and in vivo models. The 9L glioma not tumor will be used because of its well-recognized and documented radioresistant characteristics. Boundary errors are minimized by the use of matching absorption (mu a) and scattering (mu s') in a human """"""""breast box."""""""" Two and three dimensional electromechanical scans are used for locating an isolated small tumor in the human breast. Detection contrast is provided by relative increases of blood volume and contrast agent accumulation in vascular and extravascular spaces of the tumor with respect to the normal tissue. Further developments will provide hemoglobin deoxygenation, fluorescent contrast agents, mitochondrial light scattering and osmotic perturbation as additional sources of tumor/host tissue contrast in studies of 20 tumor bearing human breasts per year.
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