Magnetic resonance imaging (MRI)‐guided transurethral ultrasound therapy of the prostate: a preclinical study with radiological and pathological correlation using customised MRI‐based moulds

Abstract

Objective To characterise the feasibility and safety of a novel transurethral ultrasound (US)-therapy device combined with real-time multi-plane magnetic resonance imaging (MRI)-based temperature monitoring and temperature feedback control, to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model. To correlate ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology. Materials and methods Three dogs were treated with three targeted ablations each, using a prototype MRI-guided transurethral US-therapy system (Philips Healthcare, Vantaa, Finland). MRI provided images for treatment planning, guidance, real-time multi-planar thermometry, as well as post-treatment evaluation of efficacy. After treatment, specimens underwent histopathological analysis to determine the extent of necrosis and cell viability. Statistical analyses (Pearson’s correlation, Student’s t-test) were used to evaluate the correlation between ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology. Results MRI combined with a transurethral US-therapy device enabled multi-planar temperature monitoring at the target as well as in surrounding tissues, allowing for safe, targeted, and controlled ablations of prescribed lesions. Ablated volumes measured by cumulative thermal dose positively correlated with volumes determined by histopathological analysis (r2 0.83, P < 0.001). Post-procedural contrast-enhanced and diffusion-weighted MRI showed a positive correlation with non-viable areas on histopathological analysis (r2 0.89, P < 0.001, and r20.91, P = 0.003, respectively). Additionally, there was a positive correlation between ablated volumes according to cumulative thermal dose and volumes identified on post-procedural contrast-enhanced MRI (r2 0.77, P < 0.01). There was no difference in mean ablation volumes assessed with the various analysis methods (P > 0.05, Student’s t-test). Conclusions MRI-guided transurethral US therapy enabled safe and targeted ablations of prescribed lesions in a preclinical canine prostate model. Ablation volumes were reliably predicted by intra- and post-procedural imaging. Clinical studies are needed to confirm the feasibility, safety, oncological control, and functional outcomes of this therapy in patients in whom focal therapy is indicated.

Catheter-based ultrasound technology for image-guided thermal therapy: Current technology and applications

“…This may be achieved through rotational sweeping of devices with planar or curvilinear transducers, or stationary devices with sectored tubular transducers. Simulation and preliminary ex vivo experiments [57, 73-79], in vivo animal models [44, 46, 47, 52, 80-82], and clinical cases [55] have been described in the literature and show successful implementation of this ablation technique. Ablation localized to the transition zone has also been demonstrated in a canine model in vivo with sectored tubular applicators as a potential treatment option for BPH [48, 49].…”

“…It was also reported for monitoring of in vivo ablations in porcine liver [111] and canine prostate [36]. Several examples of successful implementation of transurethral CBUS ablation of prostate with multi-planar PRFS-based MRTI are reported in the literature [36, 46-48, 50, 52-55, 81, 82]. Ancillary studies related to diffusion-weighted imaging [80] and refinement of MR techniques for motion compensation have also resulted from similar work [76, 113, 114].…”

“…MR temperature imaging can be sensitive to susceptibility artifacts from the inserted devices themselves, movement of organs or target regions during respiration or cardiac cycle, adjacent organs or gas (lung, bowel) generating susceptibility artifacts, or phase drift over the longer duration procedure times. Recent investigations described above have demonstrated that the artifacts generated from the devices themselves can be minimized with proper selection of MR compatible materials and fabrication techniques, so that regions as close as 1-3 mm from the applicator extending to the outer treatment boundary can be effectively monitored [49, 55, 82]. Tissue motion related errors can be compensated through multi-baseline or multi-reference imaging [76, 115-117].…”

“…However CBUS technology has been or is currently under development at academic research institutions and commercial entities. Some examples of commercialized devices or those of significant commercial interest include: transurethral devices that originated in the academic domain are being further developed by companies such as Profound Medical [55] and Phillips [82]; dual-mode US arrays for percutaneous and laparoscopic applications as developed by Guided Therapy Systems [12, 25]; large split-beam HIFU devices developed by Sonacare Medical for laparoscopic ablations [124]; a 7-sided interstitial device reported by Canney et al [11] for brain ablation is of commercial interest to Carthera; HIFU-BC catheters developed by Atrionix/Johnson & Johnson [91] and ProRhythm[95, 96] to treat atrial fibrillation by ablating tissue surrounding the pulmonary vein; and Recor Medical has developed and clinically evaluated CBUS for renal denervation in the treatment of hypertension [98, 99]. Motivating factors in support of development of CBUS technology may include: has the potential to deliver fast and highly conformable volumetric ablation with short procedure times and less resource intensive than many currently used devices; devices of the type which will be in direct contact with the target tissue may be able to follow the 510k route for FDA approval for use and marketing, which requires significantly less time and expense than the alternative Pre-Market Approval (PMA); similar to HIFU, CBUS is amenable to image guidance and monitoring platforms; deployment of CBUS procedures fit closely within existing standards of practice for interventional radiologists and surgeons implementing thermal therapy.…”

Imaging modalities in focal therapy

“…Partanen et al investigated the technology in dogs using transurethral focused ultrasound monitored by MR thermometry. The technology rendered safe and promising for use in humans [38]. …”