The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves. To investigate the mechanisms involved in boiling histotripsy, a high-speed camera with a passive cavitation detection system was used to observe the dynamics of bubbles produced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0-MHz high-intensity focused ultrasound (HIFU) transducer. We observed that boiling bubbles were generated in a localized heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole-shaped lesion. A simplified numerical model describing the scattering of the incident ultrasound wave by a vapor bubble was developed to help interpret the experimental observations. Together with the numerical results, these observations suggest that the overall size of a lesion induced by boiling histotripsy is dependent on the sizes of (i) the heated region at the HIFU focus and (ii) the backscattered acoustic field by the original vapor bubble.
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.
A forward model, which predicts the scattering by human ribs of a multi-element high-intensity focused ultrasound transducer, was used to investigate the efficacy of a range of focusing approaches described in the literature. This forward model is based on the boundary element method and was described by Gélat et al (2011 Phys. Med. Biol. 56 5553-81; 2012 Phys. Med. Biol. 57 8471-97). The model has since been improved and features a complex surface impedance condition at the surface of the ribs. The inverse problem of focusing through the ribs was implemented on six transducer array-rib topologies and five methods of focusing were investigated, including spherical focusing, binarized apodization based on geometric ray tracing, phase conjugation and the decomposition of the time-reversal operator method. The excitation frequency was 1 MHz and the array was of spherical-section type. Both human and idealized rib topologies were considered. The merit of each method of focusing was examined. It was concluded that the constrained optimization approach offers greater potential than the other focusing methods in terms of maximizing the ratio of acoustic pressure magnitudes at the focus to those on the surface of the ribs whilst taking full advantage of the dynamic range of the phased array.
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