Neuronavigation-Guided Transcranial Histotripsy (NaviTH) System.

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.

Magnetic Resonance Thermometry Targeting for Magnetic Resonance-Guided Histotripsy Treatments.

OBJECTIVE: The potential of transcranial magnetic resonance (MR)-guided histotripsy for brain applications has been described in prior in vivo studies in the swine brain through an excised human skull. The safety and accuracy of transcranial MR-guided histotripsy (tcMRgHt) rely on pre-treatment targeting guidance. In the work described here, we investigated the feasibility and accuracy of using ultrasound-induced low-temperature heating and MR thermometry for histotripsy pre-treatment targeting in ex vivo bovine brain. METHODS: A 15-element, 750-kHz MRI-compatible ultrasound transducer with modified drivers that can deliver both low-temperature heating and histotripsy acoustic pulses was used to treat seven bovine brain samples. The samples were first heated to an approximately 1.6°C temperature increase at the focus, and MR thermometry was used to localize the target. Once the targeting was confirmed, a histotripsy lesion was generated at the focus and visualized on post-histotripsy MR images. DISCUSSION: The accuracy of MR thermometry targeting was evaluated with the mean/standard deviation of the difference between the locus of peak heating identified by MR thermometry and the center of mass of the post-treatment histotripsy lesion, which was 0.59/0.31 mm and 1.31/0.93 mm in the transverse and longitudinal directions, respectively. CONCLUSION: This study determined that MR thermometry could provide reliable pre-treatment targeting for transcranial MR-guided histotripsy treatment.

Transcranial Magnetic Resonance-Guided Histotripsy for Brain Surgery: Pre-clinical Investigation.

Histotripsy has been previously applied to target various cranial locations in vitro through an excised human skull. Recently, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, enabling pre-clinical investigations of tcMRgHt for brain surgery. To determine the feasibility of in vivo transcranial histotripsy, tcMRgHt treatment was delivered to eight pigs using a 700-kHz, 128-element, MR-compatible phased-array transducer inside a 3-T magnetic resonance imaging (MRI) scanner. After craniotomy to open an acoustic window to the brain, histotripsy was applied through an excised human calvarium to target the inside of the pig brain based on pre-treatment MRI and fiducial markers. MR images were acquired pre-treatment, immediately post-treatment and 2-4 h post-treatment to evaluate the acute treatment outcome. Successful histotripsy ablation was observed in all pigs. The MR-evident lesions were well confined within the targeted volume, without evidence of excessive brain edema or hemorrhage outside of the target zone. Histology revealed tissue homogenization in the ablation zones with a sharp demarcation between destroyed and unaffected tissue, which correlated well with the radiographic treatment zones on MRI. These results are the first to support the in vivo feasibility of tcMRgHt in the pig brain, enabling further investigation of the use of tcMRgHt for brain surgery.

Transcranial MR-Guided Histotripsy System.

Histotripsy has been previously shown to treat a wide range of locations through excised human skulls in vitro. In this article, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, characterized, and tested in the in vivo pig brain through an excised human skull. A 700-kHz, 128-element MR-compatible phased-array ultrasound transducer with a focal depth of 15 cm was designed and fabricated in-house. Support structures were also constructed to facilitate transcranial treatment. The tcMRgHt array was acoustically characterized with a peak negative pressure up to 137 MPa in free field, 72 MPa through an excised human skull with aberration correction, and 48.4 MPa without aberration correction. The electronic focal steering range through the skull was 33.5 mm laterally and 50 mm axially, where a peak negative pressure above the 26-MPa cavitation intrinsic threshold can be achieved. The MR compatibility of the tcMRgHt system was assessed quantitatively using SNR, B0 field map, and B1 field map in a clinical 3T magnetic resonance imaging (MRI) scanner. Transcranial treatment using electronic focal steering was validated in red blood cell phantoms and in vivo pig brain through an excised human skull. In two pigs, targeted cerebral tissue was successfully treated through the human skull as confirmed by MRI. Excessive bleeding or edema was not observed in the peri-target zones by the time of pig euthanasia. These results demonstrated the feasibility of using this preclinical tcMRgHt system for in vivo transcranial treatment in a swine model.