Optical model of the murine lung to optimize pulmonary illumination

Abstract

We describe a Monte Carlo model of the mouse torso to optimize illumination of the mouse lung for fluorescence detection of low levels of pulmonary pathogens, specifically Mycobacterium tuberculosis. After validation of the simulation with an internally illuminated optical phantom, the entire mouse torso was simulated to compare external and internal illumination techniques. Measured optical properties of deflated mouse lungs were scaled to mimic the diffusive properties of inflated lungs in vivo. Using the full-torso model, a 2 × to 3 × improvement in average fluence rate in the lung was seen for dorsal compared with ventral positioning of the mouse with external illumination. The enhancement in average fluence rate in the lung using internal excitation was 40 × to 60 × over external illumination in the dorsal position. Parameters of the internal fiber optic source were manipulated in the model to guide optimization of the physical system and experimental protocol for internal illumination and whole-body detection of fluorescent mycobacteria in a mouse model of infection.

Fluorescence modeling of in vivo optical detection of Mycobacterium tuberculosis

“…The computational model was developed in LightTools Illumination software (Synopsys Inc.), building on our previous illumination model [11]. The model incorporates the anatomy of a small animal with appropriate internal structures and optical properties.…”

“…Investigations of source manipulations did not suggest any improvement in fluorescence signal. Simulations of internal illumination showed that a broader divergence angle would result in more effective illumination of the lung [11]. However, this did not reliably translate into a significant improvement in collected fluorescence.…”

“…The external illumination source was placed 20 mm from the central plane of the simulated torso with a power output for all wavelengths of 1 mW, which is within the range of illumination for whole-animal fluorescence imaging systems with very sensitive cameras. Previous work shows that, at this scale, the dosage to the lung scales linearly with power [11]. Simulation results can therefore be easily scaled to represent specific experimental parameters.…”

“…Experimentally, placing the microendoscope in the same location in each animal is extremely difficult due to inter-animal anatomical variability. Additionally, we previously showed that the illumination of the lung by the microendoscope was dependent on source location [11]. To more accurately represent the experimental procedure, signal collection was modeled with "pseudo-random" placement of the microendoscope.…”

“…Previous work investigating the spatial distribution of light in the lung from an internal illumination source showed a slightly enhanced illumination of the lung tissue with an internal illumination source having a greater divergence angle [11]. To evaluate potential enhancement of fluorescence signal collection with a microendoscope with a higher divergence angle, we compared a source with a 40°divergence angle to the 20.5°divergence angle source.…”