In application, we seek to continue development of frequency- domain photon migration (FDPM) techniques with fluorescent contrast agent administration as a medical imaging and diagnostic modality that is based upon the propagation of low-level, non- ionizing near-infrared light. FDPM depends upon launching intensity modulated (30-200 MHz) light at the air-tissue interface and detecting the intensity-modulated wave that successfully propagates to the detector located a distance away from the incident source on the tissue surface. In the presence of a fluorescent dye, the propagating excitation wave creates a fluorescent wave with amplitude and phase delay related to the concentration of dye and decay kinetics. The decay kinetics, described by the lifetime of the fluorescent dye, varies in response to local environment and is an established spectroscopic measurement in diluted, non-scattering solutions. In this application we take advantage of the finite lifetime of fluorescent contrast agents to impart added contrast for FDPM imaging of diseased tissue volumes. The proposed method employs sophisticated multi-pixel imaging techniques, recently demonstrated by the P.I. for detecting spontaneous breast cancer in vivo in a canine model. In order to reconstruct interior optical property maps from in vivo fluorescence FDPM measurements, our proposal seeks to couple our image inversion algorithm and multi-pixel imaging technqiues. Fluorescence FDPM imaging will offer sensitivity and specificity for disease detection that arises from the exquisite sensitivity for fluorescence as recognized in clinical chemistry. In this pre- clinical work, we direct our imaging technology towards the evaluation of lymph node involvement, an area in which conventional imaging modalities perform poorly. Lymph node status in breast cancer patients is the most powerful predictor of recurrence and survival, and the number of lymph nodes with metastases provides prognostic information which can impact the choice of adjuvant-therapy. As a natural extension of our imaging work, we also further develop FDPM techniques for biosensing applications in which lifetime sensitive fluorophores embedded in an implantable polymeric matrix can provide fluorescence signals detected at the tissue-air interface. Our work focuses on Con A/Dextran moieties for diabetic glucose sensing.
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