Numerical investigation of depth-sensitive diffuse reflectance and fluorescence measurements on murine subcutaneous tissue with growing solid tumors.

In most biomedical optical spectroscopy platforms, a fiber-probe consisting of single or multiple illumination and collection fibers was commonly used for the delivery of illuminating light and the collection of emitted light. Typically, the signals from all collection fibers were combined and then sampled to characterize tissue samples. Such simple averaged optical measurements may induce significant errors for in vivo tumor characterization, especially in longitudinal studies where the tumor size and location vary with tumor stages. In this study, we utilized the Monte Carlo technique to optimize the fiber-probe geometries of a spectroscopy platform to enable tumor-sensitive diffuse reflectance and fluorescence measurements on murine subcutaneous tissues with growing solid tumors that have different sizes and depths. Our data showed that depth-sensitive techniques offer improved sensitivity in tumor detection compared to the simple averaged approach in both reflectance and fluorescence measurements. Through the numerical studies, we optimized the source-detector distances, fiber diameters, and numerical apertures for sensitive measurement of small solid tumors with varying size and depth buried in murine subcutaneous tissues. Our study will advance the design of a fiber-probe in an optical spectroscopy system that can be used for longitudinal tumor metabolism and vasculature monitoring.