Experimental Demonstration of Trans-skull Volumetric Passive Acoustic Mapping with the Heterogeneous Angular Spectrum Approach.

Real-time, three-dimensional (3D), passive acoustic mapping (PAM) of microbubble dynamics during transcranial focused ultrasound (FUS) is essential for optimal treatment outcomes. The angular spectrum approach (ASA) potentially offers a very efficient method to perform PAM, as it can reconstruct specific frequency bands pertinent to microbubble dynamics and may be extended to correct aberrations caused by the skull. Here we assesses experimentally the abilities of heterogeneous ASA (HASA) to perform trans-skull PAM. Our experimental investigations demonstrate that the 3D PAMs of a known 1MHz source, constructed with HASA through an ex vivo human skull segment, reduced both the localization error (from 4.7±2.3mm to 2.3±1.6mm) and the number, size, and energy of spurious lobes caused by aberration, with modest additional computational expense. While further improvements in the localization errors are expected with arrays with denser elements and larger aperture, our analysis revealed that experimental constraints associated with the array pitch and aperture (here 1.8mm and 2.5 cm, respectively) can be ameliorated by interpolation and peak finding techniques. Beyond the array characteristics, our analysis also indicated that errors in the registration (translation and rotation of ±5mm and ±5°, respectively) of the skull segment to the array can led to peak localization errors of the order of a few wavelengths. Interestingly, errors in the spatially dependent speed of sound in the skull (±20%) caused only sub-wavelength errors in the reconstructions, suggesting that registration is the most important determinant of point source localization accuracy. Collectively, our findings show that HASA can address source localization problems through the skull efficiently and accurately under realistic conditions, thereby creating unique opportunities for imaging and controlling the microbubble dynamics in the brain.