Real-Time Transcranial Histotripsy Treatment Localization and Mapping Using Acoustic Cavitation Emission Feedback

Cavitation events generated during histotripsy therapy generate large acoustic cavitation emission (ACE) signals that can be detected through the skull. This article investigates the feasibility of using these ACE signals, acquired using the elements of a 500-kHz, 256-element hemispherical histotripsy transducer as receivers, to localize and map the cavitation activity in real time through the human skullcap during transcranial histotripsy therapy. The locations of the generated cavitation events predicted using the ACE feedback signals in this study were found to be accurate to within <1.5 mm of the centers of masses detected by optical imaging and found to lie to within the measured volumes of the generated cavitation events in >~80 % of cases. Localization results were observed to be biased in the prefocal direction of the histotripsy array and toward its transverse origin but were only weakly affected by focal steering location. The choice of skullcap and treatment pulse repetition frequency (PRF) were both observed to affect the accuracy of the localization results in the low PRF regime (1-10 Hz), but the localization accuracy was seen to stabilize at higher PRFs (≥10 Hz). Tests of the localization algorithm in vitro, for treatment delivered to a bovine brain sample mounted within the skullcap, revealed good agreement between the ACE feedback-generated treatment map and the morphological characteristics of the treated volume of the brain sample. Localization during experiments was achieved in real time for pulses delivered at rates up to 70 Hz, but benchmark tests indicate that the localization algorithm is scalable, indicating that higher rates are possible with more powerful hardware. The results of this article demonstrate the feasibility of using ACE feedback signals to localize and map transcranially generated cavitation events during histotripsy. Such capability has the potential to greatly simplify transcranial histotripsy treatments, as it may provide a non-MRI-based method for monitoring and localizing transcranial histotripsy treatments in real time.