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

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.