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Objective: Transcranial magnetic resonance imaging (MRI)-guided histotripsy has been demonstrated to treat various locations in in vivo swine brain through a human skull. To ensure that the histotripsy treatment is delivered to the intended target location, accurate pre-treatment targeting is necessary. In this work, we investigate the feasibility of MR-thermometry and MR-acoustic radiation force imaging (MR-ARFI) to perform pre-treatment targeting of histotripsy in ex vivo bovine brain through a human skull., Methods: A 700 kHz, 128-element MR-compatible histotripsy array was used to generate histotripsy and tone-burst sonications. The array's electronic drivers were modified to also generate low-amplitude tone-burst sonications to perform MR-thermometry and MR-ARFI-based targeting. Twelve ex vivo bovine brains were treated with histotripsy at 35 MPa, 75 MPa and through a skull at 36 MPa. Before treating the tissue, both MR-ARFI and MR-thermometry were used to estimate the lesion location. Finally, the location of the histotripsy lesion was compared with the focus estimated by MR-thermometry and MR-ARFI., Results: MR-thermometry and MR-ARFI were able to successfully perform pre-treatment targeting of histotripsy using the modified histotripsy array driver. Histotripsy focus was estimated with mean absolute errors along the transverse/longitudinal axis of 2.06/2.95 mm and 2.13/2.51 mm for MR-ARFI and MR-thermometry, respectively. The presence of the human skull reduced the pressure at the focal region, but it did not compromise the targeting accuracy of either of the two methods with a mean absolute error of 1.10/2.91 mm and 1.29/2.91 mm for MR-ARFI and MR-thermometry, respectively., Conclusion: This study demonstrated that transcranial histotripsy pre-treatment targeting is feasible with MR-thermometry and MR-ARFI., Competing Interests: Conflict of interest Z.X., T.H., and the University of Michigan have financial and/or other relationships with HistoSonics Inc., (Copyright © 2024. Published by Elsevier Inc.)

Histotripsy is a noninvasive ablation technique that focuses ultrasound pulses into the body to destroy tissues via cavitation. Heterogeneous acoustic paths through tissue introduce phase errors that distort and weaken the focus, requiring additional power output from the histotripsy transducer to perform therapy. This effect, termed phase aberration, limits the safety and efficacy of histotripsy ablation. It has been shown in vitro that the phase errors from aberration can be corrected by receiving the acoustic signals emitted by cavitation. For transabdominal histotripsy in vivo, however, cavitation-based aberration correction (AC) is complicated by acoustic signal clutter and respiratory motion. This study develops a method that enables robust, effective cavitation-based AC in vivo and evaluates its efficacy in the swine liver. The method begins with a high-speed pulsing procedure to minimize the effects of respiratory motion. Then, an optimal phase correction is obtained in the presence of acoustic clutter by filtering with the singular value decomposition (SVD). This AC method reduced the power required to generate cavitation in the liver by 26% on average (range: 0%-52%) and required ~2 s for signal acquisition and processing per focus location. These results suggest that the cavitation-based method could enable fast and effective AC for transabdominal histotripsy.

Objective: The goal of the work described here was to develop the first neuronavigation-guided transcranial histotripsy (NaviTH) system and associated workflow for transcranial ablation., Methods: The NaviTH system consists of a 360-element, 700 kHz transmitter-receiver-capable transcranial histotripsy array, a clinical neuronavigation system and associated equipment for patient-to-array co-registration and therapy planning and targeting software systems. A workflow for NaviTH treatments, including pre-treatment aberration correction, was developed. Targeting errors stemming from target registration errors (TREs) during the patient-to-array co-registration process, as well as focal shifts caused by skull-induced aberrations, were investigated and characterized. The NaviTH system was used in treatments of two <96 h post-mortem human cadavers and in experiments in two excised human skullcaps., Results: The NaviTH was successfully used to create ablations in the cadaver brains as confirmed in post-treatment magnetic resonance imaging A total of three ablations were created in the cadaver brains, and targeting errors of 9, 3.4 and 4.4 mm were observed in corpus callosum, septum and thalamus targets, respectively. Errors were found to be caused primarily by TREs resulting from transducer tracking instrument design flaws and imperfections in the treatment workflow. Transducer tracking instrument design and workflow improvements reduced TREs to <2 mm, and skull-induced focal shifts, following pre-treatment aberration correction, were 0.3 mm. Total targeting errors of the NaviTH system following the noted improvements were 2.5 mm., Conclusions: The feasibility of using the first NaviTH system in a human cadaver model has been determined. Although accuracy still needs to be improved, the proposed system has the potential to allow for transcranial histotripsy therapies without requiring active magnetic resonance treatment guidance., Competing Interests: Conflict of interest T.I.G., A.S.P., Z.X. and J.R.S., and the University of Michigan have a financial interest in HistoSonics, Inc. All other authors have no financial disclosures or conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)