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

Abstract

Purpose 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. Methods sUPEs were doped with a magnetic resonance (MR) contrast agent, Gd2O3, 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. Results 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. Conclusions 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.

Assessment of histotripsy-induced liquefaction with diagnostic ultrasound and magnetic resonance imaging in vitro and ex vivo

“…Image-guided high intensity therapeutic ultrasound is a non-invasive modality for tissue ablation (Kennedy et al 2003, Kennedy 2005, Haar and Coussios 2007, Schulman et al 2017, Anthony et al 2019. Histotripsy is a form of focused ultrasound that ablates tissue via the nucleation and mechanical activity of bubble clouds, imparting lethal strain to target tissues (Parsons et al 2006, Roberts et al 2006, Khokhlova et al 2015, Bader et al 2019.…”

Functional micro/nanobubbles for ultrasound medicine and visualizable guidance

“…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 [88].…”

Indocyanine green modified silica shells for colon tumor marking

“…[70] This synthesis method is highly tunable, allowing for doping of the shell during or after growth to modify its physical or chemical properties. [52,60,71,72] In the present study, 100 nm and 2 µm shells were used.…”

“…°C ramp up to 550 °C and then a constant step at 550 °C for 5 hours [62]. 2.3.2 Synthesis of 2 µm MicroshellsThe 2 µm microshells were synthesized similar to previously described protocols [60,72]. First, 12 mL of phosphate buffered saline (PBS), 600 µL of polystyrene templates and 1680 µL of PLL were vortexed for 30 minutes in a 50 mL polypropylene tube.…”