| The goal of this research is to develop and test a new clinical technique that is capable of obtaining broadband near-infrared (typically 650–1000 nm) absorption and scattering spectra in highly-turbid materials, and applying this method to the noninvasive functional characterization of breast disease.; The initial phases of this study assemble and test the instrument, a hybrid system based on steady-state (SS) and frequency-domain photon migration (FDPM) technologies. The two systems (SSFD) can be theoretically coupled to derive a complete near-infrared absorption spectrum, a 50-fold increase in spectral content from the 7–10 discrete wavelength capability of the current state-of-the-art FDPM instruments. Design details of the steady-state system are presented, including source and calibration parameters. The theoretical framework, including both frequency-domain and steady-state solutions to the diffusion equations, is explored and a method for combining the data analysis of the two modalities is presented. The performance of the system is tested and validated on tissue-simulating phantoms. In addition, the capability of the new system to accurately quantify multiple chromophores over a range of concentrations is tested.; The final phase applies the hybrid SSFD method to breast cancer studies. In a 70-day longitudinal comparison of two patients, we monitor breast tumor changes during chemotherapy treatment for the eventual purpose of adjusting drug regimes in those patients with low or negative response. Tumors generally show elevated values of hemoglobin and water, with reduced values of lipid and tissue hemoglobin oxygen saturation. In the responding patient, we see tumor measurement values approach normal levels over the course of therapy. These changes are not observed in the nonresponder. Moreover, these changes are apparent within the first week of therapy.; The results suggest the hybrid SSFD system has excellent potential as a clinical method for non-invasively characterizing tumor physiology and response to therapy. Trials on a larger number of patients are in progress. Because of the non-ionizing, portable, and relatively inexpensive nature of this instrument, it is ideal for point-of-care measurements. It is hoped that the advances of this thesis will bring this technology one step closer to widespread clinical availability.*; *This dissertation includes a CD that is compound (contains both a paper copy and a CD as part of the dissertation). The CD requires the following applications: Windows 95 or higher, Measurement Studio 6.0 LabWindows/CVI, Matlab 6.1.0.450. |
