Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results

Abstract

Purpose: To demonstrate the feasibility of Robotically Assisted Sonic Therapy (RAST)—a noninvasive and nonthermal focused ultrasound therapy based on histotripsy—for renal ablation in a live porcine model. Materials and Methods: RAST ablations (n = 11) were performed in 7 female swine: 3 evaluated at 1 week (acute) and 4 evaluated at 4 weeks (chronic). Treatment groups were acute bilateral (3 swine, 6 ablations with immediate computed tomography [CT] and sacrifice); chronic single kidney (3 swine, 3 ablations; CT at day 0, week 1, and week 4 after treatment, followed by sacrifice); and chronic bilateral (1 swine, 2 ablations). Treatments were performed using a prototype system (VortxRx; HistoSonics, Inc) and targeted a 2.5-cm-diameter sphere in the lower pole of each kidney, intentionally including the central collecting system. Results: Mean treatment time was 26.4 minutes. Ablations had a mean diameter of 2.4 ± 0.3 cm, volume of 8.5 ± 2.4 cm3, and sphericity index of 1.00. Median ablation volume decreased by 96.1% over 4 weeks. Histology demonstrated complete lysis with residual blood products inside the ablation zone. Temporary collecting system obstruction by thrombus was observed in 4/11 kidneys (2 acute and 2 chronic) and resolved by 1 week. There were no urinary leaks, main vessel thromboses, or adjacent organ injuries on imaging or necropsy. Conclusions: In this normal porcine model, renal RAST demonstrated complete histologic destruction of the target renal tissue while sparing the urothelium.

Noninvasive thyroid histotripsy treatment: proof of concept study in a porcine model

“…Histotripsy may have decreased complications in the adjacent nerves and glandular tissue due to the noninvasive and precise nature of the treatment. The rapid involution of treatment zones seen in prior studies may be an advantage in treatment of benign nodules for symptom relief or cosmesis [17,21]. No significant hemorrhage was identified on MRI or pathology post treatment.…”

“…These are likely a reflection of using a generic pulse path and treatment dose along with a transducer which was not of an optimal f number for treatment in the neck. In prior pig liver and kidney studies, there was complete necrosis of targeted tissue despite the increased depth and inferior ultrasound window [17,21,25]. It is expected that complete necrosis would be seen with either more pulses per treatment point (i.e., higher dose) or increased overlap between adjacent focal points, two parameters that are readily programmed into the treatment algorithm.…”

“…The system consists of a 1 MHz therapeutic transducer (active aperture 4.6 Â 7.1 cm, focal length 6.0 cm, and a working distance of 4.6 cm), a 3 degrees of freedom robotic delivery system and a co-axially aligned 4 MHz phased array diagnostic transducer for realtime continuous visualization, including targeting and monitoring the procedure. The therapy transducer was directed by a proprietary planning software package which can prescribe a treatment of virtually any size, shape, and volume [17,21,25].…”

“…Histotripsy is a noninvasive, non-ionizing, non-thermal therapy, which uses short pulses of high amplitude focused ultrasound to produce cavitation and tissue destruction at the cellular level [14][15][16]. Histotripsy has been shown in preclinical models to create precise treatments with rapid resorption in multiple organs [17][18][19][20][21][22]. Yet the ability to create a treatment within the superficial anterior neck has not been shown.…”

Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound

“…There is also a limitation on the depth of the tissue that can be treated by externally delivered histotripsy due to the increasing ultrasound attenuation with increasing tissue depth which may preclude use on very obese subjects. c. Thrombosis -Histotripsy may induce thrombosis in vessels within the treated region, likely due to platelet activation and aggregation from cavitation [84]. This thrombosis effect is also observed to some degree following radiofrequency ablation and microwave ablation [85,151,152].…”