Dependence of ablative ability of high-intensity focused ultrasound cavitation-based histotripsy on mechanical properties of agar

Abstract

Cavitation-based histotripsy uses high-intensity focused ultrasound at low duty factor to create bubble clouds inside tissue to liquefy a region, and provides better fidelity to planned lesion coordinates and the ability to perform real-time monitoring. The goal of this study was to identify the most important mechanical properties for predicting lesion dimensions, among these three: Young's modulus, bending strength, and fracture toughness. Lesions were generated inside tissue-mimicking agar, and correlations were examined between the mechanical properties and the lesion dimensions, quantified by lesion volume and by the width and length of the equivalent bubble cluster. Histotripsy was applied to agar samples with varied properties. A cuboid of 4.5mm width (lateral to focal plane) and 6mm depth (along beam axis) was scanned in a raster pattern with respective step sizes of 0.75 and 3mm. The exposure at each treatment location was either 15, 30, or 60s. Results showed that only Young's modulus influenced histotripsy's ablative ability and was significantly correlated with lesion volume and bubble cluster dimensions. The other two properties had negligible effects on lesion formation. Also, exposure time differentially affected the width and depth of the bubble cluster volume. KeywordsMechanical Engineering, algae, bending strength, cavitation, elastic moduli, fracture, polysaccharides, tissue, ultrasonics, bubble clusters, high intensity focused ultrasound, lesion formation, real time monitoring, Young's Modulus, biomechanics Disciplines Electrical and Computer Engineering | Mechanical Engineering CommentsThe following article appeared in Journal of the Acoustical Society of America 136 (2014) Cavitation-based histotripsy uses high-intensity focused ultrasound at low duty factor to create bubble clouds inside tissue to liquefy a region, and provides better fidelity to planned lesion coordinates and the ability to perform real-time monitoring. The goal of this study was to identify the most important mechanical properties for predicting lesion dimensions, among these three: Young's modulus, bending strength, and fracture toughness. Lesions were generated inside tissue-mimicking agar, and correlations were examined between the mechanical properties and the lesion dimensions, quantified by lesion volume and by the width and length of the equivalent bubble cluster. Histotripsy was applied to agar samples with varied properties. A cuboid of 4.5 mm width (lateral to focal plane) and 6 mm depth (along beam axis) was scanned in a raster pattern with respective step sizes of 0.75 and 3 mm. The exposure at each treatment location was either 15, 30, or 60 s. Results showed that only Young's modulus influenced histotripsy's ablative ability and was significantly correlated with lesion volume and bubble cluster dimensions. The other two properties had negligible effects on lesion formation. Also, exposure time differentially affected the width and depth of the bubble cluster volume.

Visualizing the histotripsy process: Bubble cloud-cancer cell interactions in a tissue-mimicking environment

“…In preliminary experiments conducted without the top fibrin layer, the vast majority of cells were detached within in a single pulse, including cells farther away from the bubbles. This observation makes sense based on previous work showing that histotripsy is dependent upon tissue mechanical properties (Xu and Bigelow 2011;Vlaisavljevich et al 2014a;Vlaisavljevich et al 2014b;Xu et al 2014;Vlaisavljevich et al 2015a;Vlaisavljevich et al 2015b), which are determined by the extracellular matrix, intracellular matrix, and cellmatrix adhesions. During the multi-pulse experiments, cells at the bubble cloud boundary were deformed numerous times and often bisected multiple times before complete removal.…”

Visualizing the Histotripsy Process: Bubble Cloud–Cancer Cell Interactions in a Tissue-Mimicking Environment

“…In preliminary experiments conducted without the top fibrin layer, the vast majority of cells were detached within in a single pulse, including cells farther away from the bubbles. This observation makes sense based on previous work showing that histotripsy is dependent upon tissue mechanical properties (Xu and Bigelow 2011; Vlaisavljevich et al 2014a; Vlaisavljevich et al 2014b; Xu et al 2014; Vlaisavljevich et al 2015a; Vlaisavljevich et al 2015b), which are determined by the extracellular matrix, intracellular matrix, and cell-matrix adhesions. During the multi-pulse experiments, cells at the bubble cloud boundary were deformed numerous times and often bisected multiple times before complete removal.…”

“…Since previous work has demonstrated that tissue mechanical properties significantly impact histotripsy (Xu and Bigelow 2011; Vlaisavljevich et al 2014a; Vlaisavljevich et al 2014b; Xu et al 2014; Vlaisavljevich et al 2015a; Vlaisavljevich et al 2015b), an optically transparent fibrin-based tissue phantom with an embedded layer of human breast cancer cells (BCCs, MDAMB231) was used to mimic adherent cells inside a tissue-like ECM environment. Cell culture work was performed under ThermoForma Class II A1 Biological Safety Cabinet and cells were incubated at 37°C and 5% CO 2 .…”

<italic>Post Hoc</italic> Analysis of Passive Cavitation Imaging for Classification of Histotripsy-Induced Liquefaction <italic>in Vitro</italic>

“…The degassed agar/n-propanol solution was combined with the heated evaporated milk, poured into a mold, and allowed to solidify at 5° C. This formation has previously been shown to replicate the density, sound speed, and frequency-dependent acoustic attenuation spectra of ex vivo prostate tissue [39]. The dynamics of histotripsy bubble clouds can be significantly altered by the medium stiffness [37], [40. The concentration of agar was adjusted so that the elastic modulus of the phantom was 44 ± 0.4 kPa [41], similar to that observed in benign prostatic hyperplasia [42]–[44].…”