Transcranial ultrasound localization microscopy of the rat brain with ray theory-based aberration correction.

Transcranial ultrasound localization microscopy (t-ULM) is faced with challenges posed by the skull, including acoustic attenuation and phase aberrations. There is a significant request for an efficient aberration correction method achieving a great balance between computational complexity and accuracy. In this study, the ray theory is first applied to in-vivo transcranial imaging to calculate the traveltime table in the inhomogeneous medium model of the imaging region. The velocity model is derived through the skull segmentation, and the autofocus method is employed to estimate the longitudinal wave speed of the skull. The validity of the proposed method is substantiated through time-domain simulations and in-vivo t-ULM experiments in rat brains. Results show that the ray theory-based aberration correction enables a spatial resolution improvement of 15.3 % (about 5.3 μm) and an imaging saturation enhancement of 3.6 % on average, revealing the vessels down to 27.6 μm in diameter. Moreover, the vasculature in the cerebral cortex, affected by multiple reflections, can be reconstructed successfully by the intensity compensation. This work provides an efficient ray theory-based solution to the aberration and its first in-vivo validation in t-ULM. The effect of speed estimation errors of the rat skull on aberration correction was clarified. Ray theory-based method holds great promise for transcranial microvascular imaging.