Herein we present the development of a fluorescence-enhanced, frequency-domain radiative transport reconstruction system designed for small animal optical tomography. The system includes a time-dependent data acquisition instrument, a radiative transport based forward model for prediction of time-dependent propagation of photons in small, non-diffuse volumes, and an algorithm which utilizes the forward model to reconstruct fluorescent yields from air/tissue boundary measurements. The major components of the instrumentation include a charge coupled device camera, an image intensifier, signal generators, and an optical switch. Time-dependent data were obtained in the frequency-domain using homodyne techniques on phantoms with 0.2% to 3% intralipid solutions. Through collaboration with Transpire, Inc., a fluorescence-enhanced, frequency-domain, radiative transport equation (RTE) solver was developed. This solver incorporates the discrete ordinates, source iteration with diffusion synthetic acceleration, and linear discontinuous finite element differencing schemes, to predict accurately the fluence of excitation and emission photons in diffuse and transport limited systems. Additional techniques such as the first scattered distributed source method and integral transport theory are used to model the numerical apertures of fiber optic sources and detectors. The accuracy of the RTE solver was validated against diffusion and Monte Carlo predictions and experimental data. The comparisons were favorable in both the diffusion and transport limits, with average errors of the RTE predictions, as compared to experimental data, typically being less than 8% in amplitude and 7% in phase. These average errors are similar to those of the Monte Carlo and diffusion predictions. Synthetic data from a virtual mouse were used to demonstrate the feasibility of using the RTE solver for reconstructing fluorescent heterogeneities in small, non-diffuse volumes. The current version of the RTE solver limits the reconstruction to one iteration and the reconstruction of marginally diffuse, frequency-domain experimental data using RTE was not successful. Multiple iterations using a diffusion solver successfully reconstructed the fluorescent heterogeneities, indicating that, when available, multiple iterations of the RTE based solver should also reconstruct the heterogeneities.

Herein we present the development of a fluorescence-enhanced, frequency-domain radiative transport reconstruction system designed for small animal optical tomography. The system includes a time-dependent data acquisition instrument, a radiative transport based forward model for prediction of time-dependent propagation of photons in small, non-diffuse volumes, and an algorithm which utilizes the forward model to reconstruct fluorescent yields from air/tissue boundary measurements. The major components of the instrumentation include a charge coupled device camera, an image intensifier, signal generators, and an optical switch. Time-dependent data were obtained in the frequency-domain using homodyne techniques on phantoms with 0.2% to 3% intralipid solutions. Through collaboration with Transpire, Inc., a fluorescence-enhanced, frequency-domain, radiative transport equation (RTE) solver was developed. This solver incorporates the discrete ordinates, source iteration with diffusion synthetic acceleration, and linear discontinuous finite element differencing schemes, to predict accurately the fluence of excitation and emission photons in diffuse and transport limited systems. Additional techniques such as the first scattered distributed source method and integral transport theory are used to model the numerical apertures of fiber optic sources and detectors. The accuracy of the RTE solver was validated against diffusion and Monte Carlo predictions and experimental data. The comparisons were favorable in both the diffusion and transport limits, with average errors of the RTE predictions, as compared to experimental data, typically being less than 8% in amplitude and 7% in phase. These average errors are similar to those of the Monte Carlo and diffusion predictions. Synthetic data from a virtual mouse were used to demonstrate the feasibility of using the RTE solver for reconstructing fluorescent heterogeneities in small, non-diffuse volumes. The current version of the RTE solver limits the reconstruction to one iteration and the reconstruction of marginally diffuse, frequency-domain experimental data using RTE was not successful. Multiple iterations using a diffusion solver successfully reconstructed the fluorescent heterogeneities, indicating that, when available, multiple iterations of the RTE based solver should also reconstruct the heterogeneities.

Interparticle interactions determine the microstructure, stability, rheology, and optical properties of concentrated colloidal suspensions involved in paint, paper, cosmetic, and pharmaceutical industries, etc. Frequency domain photon migration (FDPM) involves modeling the photon transport in a multiple scattering medium as a diffusion process in order to simultaneously determine isotropic scattering and absorption coefficients from measured amplitude attenuation and phase shift of the propagating photon density wave. Using FDPM, we investigated the impact of electrostatic interaction upon the optical properties and structure of dense charged suspensions. We demonstrated that electrostatic interactions among charged polystyrene latex may significantly affect the light scattering properties and structure of dense suspensions at low ionic strength (<0.06 mM NaCl equivalent) by actual FDPM measurement. We showed that the structure factor models addressing electrostatic interaction can be used to describe the microstructure of charged suspensions and quenched scattering due to electrostatics, and demonstrated that FDPM has the potential to be a novel structure and surface charge probe for dense suspensions. We also showed that the FDPM measured isotropic scattering coefficients may respond to the change in effective particle surface charge, and displayed the potential of using FDPM for probing particle surface charge in concentrated suspensions. We presented that the interference approximation implies a linear relationship between the absorption coefficient and volume fraction of suspension. We illustrated that FDPM measured absorption coefficient varies linearly with suspension volume fraction and affirmed the interference approximation from a perspective of light absorption. The validation of the interference approximation enables us to develop the methodology for estimating absorption efficiencies and imaginary refractive indices for both particles and suspending fluid simultaneously using FDPM. We further demonstrated a novel application of FDPM measured absorption coefficients in determining pigment absorption spectra, and displayed the potential of using FDPM as a novel analytical tool in pigment and paint industry.

Frequency domain photon migration (FDPM) measurements are used to study the properties of dense colloidal dispersions with hard sphere and electrostatic interactions, which are otherwise difficult to analyze due to multiple scattering effects. Hard sphere interactions were studied using a theoretical model based upon a polydisperse mixture of particles using the hard sphere Percus Yevick theory. The particle size distribution and volume fraction were recovered by solving a non linear inverse problem using genetic algorithms. The mean sizes of the particles of 144 and 223 nm diameter were recovered within an error range of 0-15.53% of the mean diameters determined from dynamic light scattering measurements. The volume fraction was recovered within an error range of 0-24% of the experimentally determined volume fractions. At ionic strengths varying between 0.5 and 4 mM, multiple wavelength (660, 685, 785 and 828 nm) FDPM measurements of isotropic scattering coefficients were made of 144 and 223 nm diameter, monodisperse dispersions varying between 15% - 22% volume fraction, as well as of bidisperse mixtures of 144 and 223 nm diameter latex particles in 1:3, 1:1 and 3:1 mixtures varying between volume fractions of 15% - 24%. Structure factor models with Yukawa potential were computed by Monte Carlo (MC) simulations and numerical solution of the coupled Ornstein Zernike equations. In monodisperse dispersions of particle diameter 144 nm the isotropic scattering coefficient versus ionic strength show an increase with increasing ionic strength consistent with model predictions, whereas there was a reversal of trends and fluctuations for the particle diameter of 223 nm. In bidisperse mixtures for the case of maximum number of smaller particles, the isotropic scattering coefficient increased with increasing ionic strength and the trends were in conformity with MC simulations of binary Yukawa potential models. As the number of larger diameter particles increased in the dispersions, the isotropic scattering coefficients depicted fluctuations, and no match was found between the models and measurements for a number ratio of 1:3. The research lays the foundation for the determination of particle size distribution, volume fractions and an estimate of effective charge for high density of particles.