Dual-frequency ultrasound focal therapy for MRI-guided transurethral treatment of the prostate: Study in gel phantom

Ultrasound thermal therapy of localized prostate cancer offers a minimally-invasive non-ionizing alternative [1-3] to surgery and radiotherapy. MRI-controlled transurethral ultrasound prostate therapy [4-6] has previously been investigated in a pilot human feasibility study [7], by treating a small sub-volume of prostate tissue. In this study, the feasibility of transurethral dual-frequency ultrasound focal therapy has been investigated in gel phantom. A database of pelvic anatomical models of human prostate cancer patients have been created using MR clinical images. The largest prostate boundary (47 cm3) was used to fabricate an anatomical gel phantom which included various MR characteristics to mimic prostate tissues, 4 localized tumors and surrounding prostate tissues. A 9-element transurethral ultrasound applicator working in dual-frequency mode (f = 4.6/14.5 MHz) was evaluated to heat: (i) the entire prostate volume (Full prostate treatment strategy), (ii) a prostate region restricted to tumors (Focal therapy). Acoustic power of each element and rotation rate of the device were adjusted in realtime based on MR-thermometry feedback control (nine thermal slices updated every 6.2s). Experiments have been performed using dual-frequency ultrasound exposures (surface Pmax: 20W.cm-2). (i) For full prostate heating, 7 elements of the device were used to cover the entire prostate length. The heating process was completed within 35 min. Ultrasound exposures at the fundamental frequency allowed full heating of the largest prostate radii (>18 mm), while exposures at the 3rd harmonic ensured homogeneous treatment of the smallest radii. Undertreated and overtreated regions represented respectively 2% and 17% of the prostate volume. (ii) For focal therapy, the target region was optimized to maintain safe regions in the prostate and to cover all tumor-mimics. Only 5 ultrasound elements were used to treat successfully all tumor-mimics within 26 min. Undertreated and overtreated regions each represented 7% of the prostate volume. MRI-guided transurethral ultrasound procedure enables full treatment and focal therapy in human prostate geometry. Prostate volume heating was fast compared to standard HIFU prostate treatments. Dual-frequency ultrasound exposures allowed optimal heat deposition in all prostate regions. The focal therapy strategy is promising as regard to safety and could contribute to enhance the post-treatment autonomy of the patient.