  Photoacoustic computed tomography (PACT) detects light-induced ultrasound
waves to reconstruct the optical absorption contrast of the biological tissues.
Due to its relatively deep penetration (several centimeters in soft tissue),
high spatial resolution, and inherent functional sensitivity, PACT has great
potential for imaging mouse brains with endogenous and exogenous contrasts,
which is of immense interest to the neuroscience community. However,
conventional PACT either assumes homogenous optical fluence within the brain or
uses a simplified attenuation model for optical fluence estimation. Both
approaches underestimate the complexity of the fluence heterogeneity and can
result in poor quantitative imaging accuracy. To optimize the quantitative
performance of PACT, we explore for the first time 3D Monte Carlo simulation to
study the optical fluence distribution in a complete mouse brain model. We
apply the MCX Monte Carlo simulation package on a digital mouse (Digimouse)
brain atlas that has complete anatomy information. To evaluate the impact of
the brain vasculature on light delivery, we also incorporate the whole-brain
vasculature in the Digimouse atlas. The simulation results clearly show that
the optical fluence in the mouse brain is heterogeneous at the global level and
can decrease by a factor of five with increasing depth. Moreover, the strong
absorption and scattering of the brain vasculature also induce the fluence
disturbance at the local level. Our results suggest that both global and local
fluence heterogeneity contributes to the reduced quantitative accuracy of the
reconstructed PACT images of mouse brain.
