Mechanical damage induced by the appearance of rectified bubble growth in a viscoelastic medium during boiling histotripsy exposure

Abstract

In boiling histotripsy, the presence of a boiling vapour bubble and understanding of its dynamic behaviour are crucially important for the initiation of the tissue fractionation process and for the control of the size of a lesion produced. Whilst many in vivo studies have shown the feasibility of using boiling histotripsy in mechanical fractionation of solid tumours, not much is known about the evolution of a boiling vapour bubble in soft tissue induced by boiling histotripsy. The main objective of this present study is therefore to investigate the formation and dynamic behaviour of a boiling vapour bubble which occurs under boiling histotripsy insonation. Numerical and experimental studies on the bubble dynamics induced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0 MHz High Intensity Focused Ultrasound (HIFU) transducer were performed with a high speed camera. The Gilmore-Zener bubble model coupled with the Khokhlov-Zabolotskaya-Kuznetsov and the Bio-heat Transfer equations was used to simulate bubble dynamics driven by boiling histotripsy waveforms (nonlinear-shocked wave excitation) in a viscoelastic medium as functions of surrounding temperature and of tissue elasticity variations. In vivo animal experiments were also conducted to examine cellular structures around a freshly created lesion in the liver resulting from boiling histotripsy. To the best of our knowledge, this is the first study reporting the numerical and experimental evidence of the appearance of rectified bubble growth in a viscoelastic medium. Accounting for tissue phantom elasticity adds a mechanical constraint on vapour bubble growth, which improves the agreement between the simulation and the experimental results. In addition the numerical calculations showed that the asymmetry in a shockwave and water vapour transport can result in rectified bubble growth which could be responsible for HIFU-induced tissue decellularisation. Strain on liver tissue induced by this radial motion can damage liver tissue while preserving blood vessels.

Boiling Histotripsy-induced Partial Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers

“…4b. This lesion shape formation is likely to be due to the number of boiling vapour bubbles induced at the HIFU focus and the violent inertial cavitation clouds formed in between the HIFU source and the boiling bubble during the HIFU exposure 22,24 . The generation of a nonlinear shocked wavefront at the HIFU focus due to nonlinear wave propagation effects in soft tissue can dramatically increase tissue temperature to boiling temperature in a few milliseconds.…”

“…The generation of a nonlinear shocked wavefront at the HIFU focus due to nonlinear wave propagation effects in soft tissue can dramatically increase tissue temperature to boiling temperature in a few milliseconds. A boiling vapour bubble subsequently forms within this localised heated volume and grows to millimetre size due to the combination of asymmetric in a shockwave and water vapour transport (i.e., rectified bubble growth) 23,24,35 . Further interaction between incoming incident shockwaves and the acoustic fields backscattered by the boiling bubble can result in the formation of a cavitation cluster in front of the bubble progressing toward the HIFU source (Supplementary Fig.…”

“…S5a) 22,36 . Shear stresses produced around an oscillating a boiling bubble at the HIFU focus may cause mechanical tissue damage 24 , whereas emissions of micro-jetting and shockwaves resulting from a cavitation cluster enable the mechanical disruption of tissue (Supplementary Fig. S5b) 7,22,30,32 .…”

“…The ultrasound exposure conditions employed in this study were well within the range of required exposure conditions reported by other boiling histotripsy studies 7,10,11,22 . Therefore, boiling vapour bubbles and cavitation clouds, which occur during the course of boiling histotripsy exposure and are responsible for mechanical tissue fractionation 7,22–24 , were expected to be formed within the HIFU focal zone in the collagen gel during each HIFU pulse. Acoustic properties of the collagen gel used in the KZK simulation are shown in Supplementary Table S1.

Figure 3HIFU pulsing protocol used in the present study.

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Modeling tissue-selective cavitation damage

“…Cavitation has been studied extensively for hydrodynamic applications and is known to erode even the hardest steels (Richman et al 1995). Recently, interest has grown in cavitation damage to biological materials including tissue (Mancia et al 2017, Pahk et al 2019) and surgical mesh (Bigelow et al 2019) given its relevance to therapeutic ultrasound and traumatic injuries. Cavitation is a potential source of neuron damage in blast traumatic brain injury (Goeller et al 2012, Estrada et al 2017, Franck 2017), and it has also been proposed as a useful context in which to study tissue damage incurred through high-strain-rate injuries (Estrada et al 2018).…”