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

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. Keywords: thermal ablation, therapeutic ultrasound, thermotherapy, minimally invasive therapy, magnetic resonance imaging, image-guided therapy Introduction Prostate cancer remains a leading medical problem in the USA. The introduction of PSA screening and earlier diagnosis of prostate cancer has shifted the treatment paradigm toward more localised therapy. In fact, up to 75% of patients are found to have localised disease [1]. Current whole-gland therapy offers the highest oncological efficacy in exchange for significant morbidities, which has motivated a growing interest in focal or regional treatment strategies that can achieve comparable oncological efficacy with minimal adverse effects on sexual and urinary function [2, 3]. Multiple phase I focal therapy trials, predominantly using cryotherapy, have shown the feasibility, safety, short-term oncological control, and minimal adverse effects profile [3]. Similar results were achieved in preliminary trials using laser-induced focal thermoablation of prostate cancer [3]. High temperatures (≥ 55 °C) are known to cause cytotoxic effects; a phenomenon defined as thermoablation [3-7]. Therapeutic ultrasound (US) is an emerging treatment method capable of achieving thermoablation in the prostate. US therapy may be used with either US or MRI guidance. Limitations of US include imprecise temperature monitoring, low sensitivity on cancer detection, and lack of three-dimensional (3D) imaging information. On the other hand, MRI can be used for monitoring real-time temperature changes in multiple planes, as well as for multi-parametric cancer detection, treatment planning, and for prediction of the extent of cell death using such sequences as contrast-enhanced imaging (CEI) and diffusion-weighted imaging (DWI). Coupling therapeutic US with MRI guidance may be particularly efficacious for focal, regional, or whole-gland therapy of prostate cancer [7]. Preliminary clinical trials using transrectal high-intensity focused US (HIFU) for focal ablation of prostate cancer have reported fewer adverse events than traditional whole-gland therapy, suggesting that targeted focal or regional therapy may be safer [5, 8]. Despite these advances, transrectal HIFU has been complicated by long treatment times, incomplete cancer treatment (especially for anterior lesions), erectile dysfunction, urinary incontinence, urethral stricture, and even recto-urethral fistulae. In comparison, transurethral US therapy has the potential to provide an even greater safety profile, while enabling targeted focal, regional, or whole-gland therapy of prostate cancer. Chopra et al. [9] and Siddiqui et al. [10] have successfully demonstrated regional prostate ablations in the clinic using a transurethral device. The objective of the present study was to evaluate the feasibility and safety of a novel transurethral US-therapy device combined with real-time multi-plane MRI-based temperature monitoring and temperature feedback control to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model. Moreover, we report on ablation spatiotemporal accuracy and correlate ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology.