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Merck

MRI-guided transurethral insonation of silica-shell phase-shift emulsions in the prostate with an advanced navigation platform.

Medical physics (2018-11-11)
Gregory J Anthony, Kenneth B Bader, James Wang, Marta Zamora, Allison Ostdiek, Tatjana Antic, Sascha Krueger, Steffen Weiss, William C Trogler, Sarah L Blair, Andrew C Kummel, Steffen Sammet
RÉSUMÉ

In this study, the efficacy of transurethral prostate ablation in the presence of silica-shell ultrasound-triggered phase-shift emulsions (sUPEs) doped with MR contrast was evaluated. The influence of sUPEs on MR imaging assessment of the ablation zone was also investigated. sUPEs were doped with a magnetic resonance (MR) contrast agent, Gd2 O3 , to assess ultrasound transition. Injections of saline (sham), saline and sUPEs alone, and saline and sUPEs with Optison microbubbles were performed under guidance of a prototype interventional MRI navigation platform in a healthy canine prostate. Treatment arms were evaluated for differences in lesion size, T1  contrast, and temperature. In addition, non-perfused areas (NPAs) on dynamic contrast-enhanced (DCE) MRI, 55°C isotherms, and areas of 240 cumulative equivalent minutes at 43°C (CEM43 ) dose or greater computed from MR thermometry were measured and correlated with ablated areas indicated by histology. For treatment arms including sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area ranged from 0.96-0.99, 0.98-0.99, and 0.91-0.99, respectively. In the absence of sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area were 0.69, 0.54, and 0.50, respectively. Across all treatment arms, the areas of thermal tissue damage and NPAs were not significantly different (P = 0.47). Areas denoted by 55°C isotherms and 240 CEM43 dose boundaries were significantly larger than the areas of thermal damage, again for all treatment arms (P = 0.009 and 0.003, respectively). No significant differences in lesion size, T1 contrast, or temperature were observed between any of the treatment arms (P > 0.0167). Lesions exhibiting thermal fixation on histological analysis were present in six of nine insonations involving sUPE injections and one of five insonations involving saline sham injections. Significantly larger areas (P = 0.002), higher temperatures (P = 0.004), and more frequent ring patterns of restricted diffusion on ex vivo diffusion-weighted imaging (P = 0.005) were apparent in lesions with thermal fixation. T1 contrast suggesting sUPE transition was not evident in sUPE treatment arms. The use of MR imaging metrics to predict prostate ablation was not diminished by the presence of sUPEs. Lesions generated in the presence of sUPEs exhibited more frequent thermal fixation, though there were no significant changes in the ablation areas when comparing arms with and without sUPEs. Thermal fixation corresponded to some qualitative imaging features.