Elastic Scattering Spectroscopy is a promising in vivo technique for estimating the size of nuclei in epithelial tissues. Since increased nuclear size is a major morphopathologic sign of tissue progression towards cancer, this technique has been pursued by researchers who demonstrated
cancer detection using it in an endoscopic point-test modality. For clear practical reasons related to future clinical use, we proposed and undertook expanding this spectroscopic tool into a true two-dimensional imaging modality. The overall objective of the research presented in this dissertation was to transform a promising spectroscopic test for early cancer detection in epithelial tissues into an in vivo/intrasurgical diagnostic imaging method, with lung cancer detection as the first application. The first specific aim was to develop an imaging system conceptually similar to the point-test one, but capable of rapidly acquiring a spectral image datacube. This was achieved, using novel hardware, software and optical design; all relevant performance parameters were met or exceeded. The second specific aim was the construction of a mathematical model for image content prediction, parameter evaluation, and optimization. This was also accomplished, and the intermediate (one-dimensional) results are consistent with the literature. The third specific aim was to verify the model against known targets (in vitro phantoms). This work was partially successful, and helped identify additional experimental parameters that needed attention when building the imaging system. The fourth specific aim was use of the newly constructed system with consenting patients, in clinical procedures. In the first of these studies (30 patients), results were inconclusive because of all-negative biopsies, but functionality, operating room compatibility and adoption were demonstrated. In the second study, still ongoing, our imaging system was used to guide biopsies (21 patients), and results are currently being analyzed and compared to histopathology. Finally, since the initial system did not take into account all key parameters revealed during the progress of this dissertation, an improved next-generation system is specifically outlined. Overall, this work underscores the usefulness of advanced engineering in general and optical imaging in particular in constructing a new clinical diagnostic system aimed at early detection of cancer without use of contrast agents.
