Profound Medical (Canada)

To report the 3-year follow-up of a Phase I study of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12-month safety and ablation precision were previously described. As a mandated safety criterion, TULSA was delivered as near whole-gland ablation, applying 3-mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12-month biopsy and MRI, biannual follow-up included prostate-specific antigen (PSA), adverse events (AEs), and functional quality-of-life assessment, with repeat systematic biopsy at 3years. A 3-year follow-up was completed by 22 patients. Between 1 and 3years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1year and was stable at 3years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33(0.1-0.4) ng/mL, stable to 0.8(0.4-1.6)ng/mL at 3years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir. With 3-year Phase I follow-up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.

Purpose To characterize temperature fields and tissue damage profiles of large-volume hyperthermia (HT) induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) in deep and superficial targets in vivo in a porcine model. Methods Nineteen HT sessions were performed in vivo with a commercial MRgHIFU system (Sonalleve® V2, Profound Medical Inc., Mississauga, ON, Canada) in hind leg muscles of eight pigs with temperature fields of cross-sectional diameter of 58-mm. Temperature statistics evaluated in the target region-of-interest (tROI) included accuracy, temporal variation, and uniformity. The impact of the number and location of imaging planes for feedback-based temperature control were investigated. Temperature fields were characterized by time-in-range (TIR, the duration each voxel stays within 40–45 °C) maps. Tissue damage was characterized by contrast-enhanced MRI, and macroscopic and histopathological analysis. The performance of the Sonalleve® system was benchmarked against a commercial phantom. Results Across all HT sessions, the mean difference between the average temperature (Tavg) and the desired temperature was −0.4 ± 0.5 °C; the standard deviation of temperature 1.2 ± 0.2 °C; the temporal variation of Tavg for 30-min HT was 0.6 ± 0.2 °C, and the temperature uniformity was 1.5 ± 0.2 °C. A difference of 2.2-cm (in pig) and 1.5-cm (in phantom) in TIR dimensions was observed when applying feedback-based plane(s) at different locations. Histopathology showed 62.5% of examined HT sessions presenting myofiber degeneration/necrosis within the target volume. Conclusion Large-volume MRgHIFU-mediated HT was successfully implemented and characterized in a porcine model in deep and superficial targets in vivo with heating distributions modifiable by user-definable parameters.

High intensity focused ultrasound (HIFU) is rapidly advancing as an alternative therapy for non-invasively treating specific cancers and other pathological tissues through thermal ablation. A new type of HIFU therapy—boiling histotripsy (BH)—aims at mechanical fractionation of into subcellular fragments, with a range of accompanying thermal effects that can be tuned from none to substantial depending on the requirements of the application. The degree of mechanical tissue damage induced by BH has been shown to depend on the tissue type, with collagenous structures being most resistant, and cellular structures being most sensitive. This has been reported for single BH lesions, but has not been replicated in large volumes. Such tissue selectivity effect has potential uses involving tissue decellularization for biofabrication technologies as well as mechanical ablation by BH while sparing critical structures. The goal of this study was to investigate tissue decellularization effect in larger, clinically relevant liquefied volumes of tissue, and to evaluate the accumulated thermal effect in the volumetric lesions under different exposure parameters. All BH exposures were performed with a 256-element 1.2 MHz array of a magnetic resonance imaging—guided HIFU (MR-HIFU) clinical system (Sonalleve V1, Profound Medical Inc, Mississauga, Canada). The volumetric BH lesions were produced in degassed ex vivo bovine liver using 1–10 ms long pulses with in situ shock amplitudes of 75–100 MPa at the focus and pulse repetition frequencies (PRFs) of 1–10 Hz covering a range of effects from pure mechanical homogenization to thermal ablation. Multimodal analysis of the lesions was then performed, including microstructure (histological), ultrastructure (electron microscopy), and molecular (biochemistry) methods. Results show a range of tissue effects in terms of the degree of tissue selectivity and the amount of heat generated in large BH lesions, thereby demonstrating potential for treatments tailored to different clinical applications.

Purpose: Magnetic resonance imaging-guided high-intensity-focused ultrasound (MR-HIFU) is a non-invasive treatment modality that precisely focuses ultrasound energy within a tumour and can be customised to result in a wide range of local bioeffects. The purpose of this study was to determine the feasibility of using MR-HIFU to treat soft tissue sarcoma (STS) in dogs.Materials and methods: Medical records of dogs admitted to the Virginia-Maryland College of Veterinary Medicine from 1 January 2012 to 31 December 2016 were searched for a diagnosis of sarcoma with available cross-sectional imaging of the tumour (MRI or CT). Fifty-three (53) dogs were eligible for inclusion. Tumor tissue (in bone as well as in soft tissue) was considered targetable unless: (1) the ultrasound path was completely obstructed by bone or gas and (2) the MR-HIFU target was within the spinal cord or less than 1 cm from the margin of the spinal cord. Tumors were categorised as <50% targetable, ≥50% targetable or non-targetable.Results: Eighty-one percent of STS (81.1%, 43/53) were targetable. The head/spine tumour sites had the highest proportion of non-targetable tumours (36%, 9/25). The majority of truncal and axillary tumours were ≥50% targetable (88.9%, 16/18) ,and all extremity tumours were considered ≥50% targetable (100%, 5/5).Conclusions: The majority of STS were targetable. This is the first study to evaluate MR-HIFU targetability of canine STS. HIFU has potential as a therapeutic modality for treating STS in dogs, and this veterinary application is a possible model for treatment of naturally occurring STS in humans.