| A new optical imaging modality has been developed for the detection of early breast disease enhanced with a fluorescent contrast agent that excites and reemits at near-infrared (NIR) wavelengths. This new modality is based on exciting the fluorescent agent using an expanded, intensity-modulated NIR light source and detecting diffuse, intensity-modulated NIR fluorescent light, or fluorescence frequency-domain photon migration (FDPM), using a gain-modulated intensified charge-coupled device (ICCD) camera system. In order to localize tissue-laden, fluorescence-enhanced targets from measurements acquired external to tissues, an inverse problem must be solved. Interior maps of tissue properties, which govern light transport, are iteratively updated by a tomographic reconstruction algorithm until experimental fluorescence data acquired external to tissues approximate data predicted by an appropriate mathematical model of light transport within tissues.; Area illumination and area detection, which have been designed to occur on the same tissue surface, are ideally suited for the clinic given their ease of implementation. Furthermore, area illumination can be used to efficiently excite fluorophores within a large tissue volume, and area detection can be used to provide large amounts of data, which benefit the underdetermined inverse problem. Measurement precision (reproducibility), measurement accuracy (agreement with a mathematical model), the target depth, and the target-to-background (T/B) ratio of fluorescent agent crucially impact whether target localization via tomographic reconstruction is feasible. Hence, important contributions in this work include: (1) determining the data acquisition parameters that maximize measurement precision; (2) developing a technique to spatially resolve the modulation amplitude and phase of the incident, area excitation source, which are needed to accurately compute the fluorescence FDPM data predicted by the mathematical model; (3) demonstrating that the coupled photon diffusion equations can be used to reasonably model experimental fluorescence FDPM data acquired from several 512-mL, homogeneous tissue phantoms, or tissue-mimicking media, each containing a 1-mL target immersed either 1 or 2 cm deep and enhanced with either a 1-μM solution of indocyanine green (ICG) or a 1.4-μM solution of 3,3′-diethylthiatricarbocyanine iodide (DTTCI); and (4) demonstrating how the target depth and the TB ratio of fluorescent agent impact the detectability of the target. |
