Time-resolved photon migration in bi-layered tissue models.

In this article, we describe a novel Monte Carlo code for time-integrated and time-resolved photon migration simulations of excitation and fluorescent light propagation (with reabsorption) in bi-layered models of biological tissues. The code was experimentally validated using bi-layered, tissue-simulating phantoms and the agreement between simulations and experiment was better than 3%. We demonstrate the utility of the code for quantitative clinical optical diagnostics in epithelial tissues by examining design characteristics for clinically compatible waveguides with arbitrarily complex source-detector configurations. Results for human colonic tissues included a quantitative comparison of simulation predictions with time-resolved fluorescence data measured in vivo and spatio-temporal visualizations of photon migration characteristics in tissue models in both two- and three-dimensions for source-detector configurations, including variable waveguide spacing, numerical aperture, and diameter. These results were then extended from surface point spectroscopy to imaging modalities for both time-gated (fluorescence lifetime) and steady-state (fluorescence intensity) experimental conditions. To illustrate the flexibility of this computational approach, time-domain results were extended to simulate predictions for frequency-domain instrumentation. This work is the first demonstration and validation of a time-domain, multi-wavelength photon transport model with these capabilities in layered turbid-media.