Contrast enhancement for diffuse optical spectroscopy and imaging: Phase cancellation and targeted fluorescence in cancer detection

Diffuse optical spectroscopy (DOS) and tomography (DOT) using Near-Infrared (NIR) light provide promising tools for non-invasive imaging and clinical diagnosis of deep tissue. These techniques are capable of quantitative reconstructions of tissue absorption and scattering properties, thus can map in vivo tissue oxygen saturation level and hemoglobin concentration. Potential clinical applications of DOS/DOT include functional neuro-imaging and tumor detection.; DOS and DOT target the contrasts from intrinsic tissue chromophores such as oxygenated and deoxygenated hemoglobin and extrinsic optical contrast agents such as Indocyanine Green (ICG). Fluorescence imaging also gives high sensitivity and specificity for biomedical diagnosis. Recent developments on specific-targeting fluorophores such as molecular beacons offer high contrast between normal and cancerous tissues, hence provide promising means for early tumor detection.; In this work, we study the contrast enhancement by applying the dual-interfering-source or so called phased array method. In-phase and out-of-phase sources generate an interference-like pattern, which cancels the background signals. The perturbation introduced by small objects allows for enhanced detection sensitivity. A frequency-domain instrument has been developed to realize the absorption and fluorescence detection. We compare the detection sensitivity for single- and dual-source by signal to noise analysis and show that the dual-source method provides higher detection sensitivity. Also, two or three-dimensional localization of an absorptive or fluorescent object embedded in the turbid media is achieved by mechanical scanning of the phased array.; To account for the effects of the heterogeneous background and finite boundaries, we also developed an amplitude modulation phased array system with electro-optic sweeping of the cancellation plane. The ability of tumor detection is demonstrated by an in vivo mouse tumor model with the systematic administration of fluorescence contrast agent, NIRF-2DG, which targets the tumor hyper-metabolism. Using the mouse tumor model and matching fluid having similar optical properties as the human breast tissue, we further explore the relations between fluorophore concentration and the detection signal.