Accurate calculation of internal fluence excited in tissue from an optical source can be used for predicting the performance of fluorescent contrast agents for clinical applications. Solutions of excitation fluence for a steady-state Monte Carlo model and a finite element implementation of the 3d diffusion equation have been compared up to depths of 20mm from a point source located on top of a homogeneous cylindrical phantom for a range of reduced scattering-to-absorption ratios. Differences between the fluence calculated by Monte Carlo and diffusion model is found to be dependent on the transport mean free path (mfp), size of the phantom in relation to the penetration depth, distance from the source and mesh resolution. The differences are small at depths ~ mfp and peak at depths ~2mfp. The differences should ideally reduce to zero at large depths but the magnitude of the differences tend to increase due to the finite boundary in the diffusion model. As an example, for a mfp = 0.817mm similar in magnitude to mesh resolution, diffusion fluence at 1mm, 2mm, 10mm and 14mm is 76%, 59%, 66% and 63% respectively of Monte Carlo fluence. For large mfp's characteristic of non- diffusive regimes, diffusion model overestimates fluence at distances less than one mfp. This work demonstrates that mean free path and mesh resolution are the critical parameters that distinguish the performance of Monte Carlo and diffusion models to define error margins that could be utilized for predictive assessment of imageability of fluorescent agents using the diffusion model.
A diffusion approximation to the radiative transfer in a medium with varying refractive index has been proposed as a theoretical model for the ultrasonic tagging of fluorescence or FluoroSound, in a scattering medium. It has been found that the diffuse modulation is a defocusing effect. Defocusing is related to scatter - more the scatter, more the defocusing and there exists a component of the defocusing effect of scatter at the ultrasonic frequency. This is in contrast to the modulation for ballistic photons that originates in the focusing effect of the acoustic lens created by the ultrasonic wave. Simulations with circular phantoms of 1.5 and 2.0cm radius have shown that defocusing is minimum when the acoustic lens is midway between the source and the detector. These results are consistent with physics and demonstrate the capability of the model to function as a predictive tool for FluoroSound instrument design. Both ballistic and diffuse FluoroSound signatures can help in the simultaneous localization of the anomaly and determination of its optical properties. As an adjunct, optimally designed ultrasound beams can be also used to enhance diffuse photon modulation signal through acoustic guidance. Optical properties provide a way to discriminate between normal and diseased tissue. FluoroSound could therefore potentially achieve a fusion of anatomical and functional information non-invasively in a single measurement. The additional information made available by this method will improve the speed and accuracy of optical imaging as a tool in the identification and validation of targets.