Photonics-based strategies for minimally invasive cancer diagnosis using endogenous and molecular contrast
Drezek, Rebekah A.
Doctor of Philosophy
Optical- and spectroscopic-based screening and imaging strategies possess unique advantages for minimally invasive cancer diagnosis. In this dissertation, we investigated how diagnostic results based on such techniques can be improved by the utilization of both endogenous and nanotechnology-facilitated molecular contrast. First, a diffusion-theory-based inversion reflectance model was constructed for the extraction of intrinsic tissue optical properties from the shape of normalized tissue diffusion reflectance spectra. The accuracy of our diffusion-based inversion algorithm was systematically assessed against Monte Carlo simulation as a function of probe geometry and tissue optical property combinations. By using this method, the spectral absorption and scattering coefficients of normal and cancerous tissue were efficiently retrieved within the center-to-center source-detector fiber separation of 0.5 mm ∼3 mm, which is compatible with endoscopic specifications. The presented inversion approach is computationally viable for eventual real-time in vivo tissue diagnostic applications. Second, novel quantum dot nanoparticle-based contrast agents were developed for molecular and tissue imaging applications in the visible and near-infrared (NIR) spectral ranges. Specifically, lead sulfide quantum dot bioconjugates were explored as NIR contrast agents for targeted molecular imaging; a protease-activated quantum dot probe was developed to monitor specific molecular targets and pathways through optical strategies; and a phantom study was conducted to assess the utilization of lead sulfide NIR quantum dots as fluorescent contrast agents for deep tissue imaging applications. These nanoengineered exogenous probes were shown to have the potential to significantly improve the implementation of optical/spectroscopic cancer imaging techniques. Taken together, the goal of the combined projects in this dissertation was to demonstrate that photonics-based minimally invasive cancer detection and imaging methods can be greatly advanced by the utilization of both endogenous and nanotechnology-facilitated molecular contrast.
Biomedical engineering; Optics