MRI-guided Transurethral Ultrasound Prostate Tissue Ablation and Delivery of Theragnostic Silica Microshells with an Advanced Navigation Platform


To evaluate the capacity of silica-shelled ultrasound-triggered phase-shift emulsions (Gd2O3-sUPEs) for enahanced imaging and treatment with transurethral ultrasound ablation (TULSA).


Phase shift emulsions were doped with an MR contrast agent, Gd2O3 to assess ultrasound transition. Randomized injections of three treatment arms (saline sham, Gd2O3-sUPEs alone, and Gd2O3-sUPEs with Optison microbubbles) were performed under guidance of a prototype interventional MRI navigation platform (Interventional MRI Suite (iSuite), Philips Research, Hamburg, Germany) in a healthy canine prostate. Ablations were evaluated for differences in lesion size, T1 contrast, and temperature. In addition, non-perfused areas (NPAs) on DCE MRI, and areas of 240 CEM43 dose boundaries computed from MR thermometry were also assessed, and correlated with histologically-determined lesion sizes. The incidence of lesions with thermally-fixed, “ring-shaped” histologies was compared between saline and non-saline (Gd2O3-sUPEs and Gd2O3-sUPEs with Optison) treatment arms. Lesion sizes and temperatures were also compared between ring-shaped and non-ring-shaped histologies.


The morphology of arms containing sUPEs had “ring-shaped” lesions, indicating rapid theramal fixation. No significant differences in lesion size, T1 contrast, or temperature were observed between any of the treatment arms. There were no significant differences in areas of lesions, 240 CEM43 dose boundaries, or NPAs between treatment arms.  A significant correlation was observed between the lesion area and 240 CEM43 area and the lesion area and NPA for the sUPEs and sUPEs with Optison arms, but not the saline sham arm. Lesions exhibiting thermal fixation and ring-shaped histologies were significantly more frequent in treatment arms involving Gd2O3-sUPE injections (p = 0.03). No ring-shaped lesions occurred in the saline control treatment arm. Significantly larger areas (p = 0.001) and higher temperatures (p = 0.001) were measured among ring-shaped lesions.


Gd2O3-sUPEs with and without Optison improved the accuracy of DCE MRI and MR thermography-derived thermal dose in estimating histological ablation sizes over the saline control treatment arm. Although there was no no significant change in ablation size for insonation of sUPEs, the lesion morphology was consistent with rapid thermal fixation. These studies suggest the addition of sUPEs will improve both the treatment efficacy and assessment of treatment outcome.