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 (r(2) 0.83, P < 0.001). Post-procedural contrast-enhanced and diffusion-weighted MRI showed a positive correlation with non-viable areas on histopathological analysis (r(2) 0.89, P < 0.001, and r(2) 0.91, 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 (r(2) 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: image-guided therapy; magnetic resonance imaging; minimally invasive therapy; therapeutic ultrasound; thermal ablation; thermotherapy.

© 2013 BJU International.

Figures

Figure 1

Schematic of the MRI-guided US therapy setup. The sagittal imaging plane is shown, with the dog supine on the MRI table top, and the US applicator shown in red is advanced along the urethra to the level of the prostate. The central three axial imaging slice positions for the thermometry sequence are shown with yellow dashed lines, and the two MRI coils are depicted in blue. Depiction of the applicator and its eight transducer elements as triangles within the prostate are meant to be illustrative. A, P, F, and H denote anterior, posterior, feet, and head, respectively.

Figure 2

Planning and temperature mapping for a focal prostate ablation using MRI-guided US therapy. A and B) Prostate was clearly identified on the T2-weighted axial and sagittal planning images, and a temperature feedback control point within the prostate was prescribed (green circle). The red overlay shows the position of the US applicator, and the dashed yellow lines depict the position of the imaging slices (A shows the slice position in B, and B shows the slice position in A). Depiction of applicator within the prostate is meant to be illustrative. C and D) Colour-coded temperature maps overlaid on dynamic magnitude images during a sonication (using four transducer elements), showing typical temperature distribution at the end of a 124 s sonication. Temperature monitoring and control was achieved in the target location with fast-field echo (FFE)-echo planar imaging (EPI) sequence, using the PRFS method for temperature mapping, and by using a binary temperature feedback algorithm. B and D are the sagittal image planes corresponding to A and C, respectively.

Figure 3

Representative examples of mean (solid), standard deviation (dotted) and maximum (dashed) temperatures over a 124 s sonication, analysed from the axial slices. The maximum temperature curve shows the measured maximum temperature within the heated region, while the mean temperature curve depicts the mean temperature with standard deviations within the predefined control point (5 voxels). Sonication was automatically stopped when the control point mean temperature reached 56 °C.

Figure 4

Representative examples of A) CEI showing non-perfused regions, B) DWI (b-value = 2000) showing greater diffusion in ablated regions, C) CK8 stained tissue showing areas of non-viable tissue, and D) real-time cumulative thermal dose estimates. Ablated volumes on histology appear slightly distorted compared with MRI due to differences in tissue slice position and shrinkage secondary to formalin fixation.

Figure 5

Correlation of histology and MRI-ablation volume estimates for all independent sonications. A) Histologically non-viable tissue as a function of thermal dose, where CEM43 > 240 was used as the threshold for tissue necrosis. B) Histologically non-viable tissue as a function of non-perfused volumes on post-treatment CEI. C) Histologically non-viable tissue as a function of ablated volumes on DWI. D) Non-perfused volumes on post-treatment CEI as a function of thermal dose.