Experimental observations of the growth and collapse of acoustically and laser-nucleated single bubbles in water and agarose gels of varying stiffness are presented. The maximum radii of generated bubbles decreased as the stiffness of the media increased for both nucleation modalities, but the maximum radii of laser-nucleated bubbles decreased more rapidly than acoustically nucleated bubbles as the gel stiffness increased. For water and low stiffness gels, the collapse times were well predicted by a Rayleigh cavity, but bubbles collapsed faster than predicted in the higher stiffness gels. The growth and collapse phases occurred symmetrically (in time) about the maximum radius in water but not in gels, where the duration of the growth phase decreased more than the collapse phase as gel stiffness increased. Numerical simulations of the bubble dynamics in viscoelastic media showed varying degrees of success in accurately predicting the observations.
Histotripsy is a noninvasive, non-thermal ablation technique that uses high-amplitude, focused ultrasound pulses to fractionate tissue via acoustic cavitation. The goal of this study was to show the potential of histotripsy with electronic focal steering to achieve rapid ablation of a tissue volume at a rate matching or exceeding current clinical techniques (~1–2 mL/min). Treatment parameters were established in tissue-mimicking phantoms and applied to ex vivo tissue. 6-μs pulses were delivered by a 250 kHz array. The focus was electrically steered to 1000 locations at 200 Hz PRF (0.12 % duty cycle). MRI and histology of the treated tissue shows a distinct region of necrosis in all samples. Mean lesion volume was 35.6 ± 4.3 mL, generated at 0.9–3.3 mL/min, a speed faster than any current ablation method for a large volume. These results suggest that histotripsy has the potential to achieve noninvasive, rapid, homogenous ablation of a tissue volume.
Following the collapse of a cavitation bubble cloud, residual microbubbles can persist for up to seconds and function as weak cavitation nuclei for subsequent pulses in a phenomenon known as cavitation memory effect. In histotripsy, the cavitation memory effect can cause bubble clouds to repeatedly form at the same discrete set of sites. This effect limits the efficacy of histotripsy-based tissue fractionation. Our previous studies have shown that low-amplitude bubble coalescing (BC) ultrasound sequences interleaved between high-amplitude histotripsy pulses can coalescence the residual bubbles into one large bubble quickly. This reduces the cavitation memory effect and may increase treatment efficacy. Histotripsy has been investigated for thrombolysis by breaking up clots to debris smaller than red blood cells. However, this treatment has low efficacy for aged or retracted clot. In this study, we investigate the use of histotripsy with BC to improve the treatment efficacy for retracted clots. An integrated histotripsy and bubble coalescing (HBC) transducer system with specialized electronic driving system was built in-house. One high amplitude (32 MPa), 1-cycle histotripsy pulse followed by 36 low amplitude (2.4 MPa), 1-cycle BC pulses formed one HBC sequence. Results show that HBC sequences successfully generated a flow channel through the retracted clots under scan speeds of 0.2 – 0.5 mm/s. The created channel size was 128–480% larger using the HBC sequence compared to using histotripsy alone. The clot debris particles generated during HBC treatments were within the safe range. These results demonstrate the concept that BC improves treatment efficacy of histotripsy thrombolysis for retracted clots.
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