Single clouds of cavitation bubbles, driven by 254kHz focused ultrasound at pressure amplitudes in the range of 0.48-1.22MPa, have been observed via high-speed shadowgraphic imaging at 1×10(6) frames per second. Clouds underwent repetitive growth, oscillation and collapse (GOC) cycles, with shock-waves emitted periodically at the instant of collapse during each cycle. The frequency of cloud collapse, and coincident shock-emission, was primarily dependent on the intensity of the focused ultrasound driving the activity. The lowest peak-to-peak pressure amplitude of 0.48MPa generated shock-waves with an average period of 7.9±0.5μs, corresponding to a frequency of f0/2, half-harmonic to the fundamental driving. Increasing the intensity gave rise to GOC cycles and shock-emission periods of 11.8±0.3, 15.8±0.3, 19.8±0.2μs, at pressure amplitudes of 0.64, 0.92 and 1.22MPa, corresponding to the higher-order subharmonics of f0/3, f0/4 and f0/5, respectively. Parallel passive acoustic detection, filtered for the fundamental driving, revealed features that correlated temporally to the shock-emissions observed via high-speed imaging, p(two-tailed) < 0.01 (r=0.996, taken over all data). Subtracting the isolated acoustic shock profiles from the raw signal collected from the detector, demonstrated the removal of subharmonic spectral peaks, in the frequency domain. The larger cavitation clouds (>200μm diameter, at maximum inflation), that developed under insonations of peak-to-peak pressure amplitudes >1.0MPa, emitted shock-waves with two or more fronts suggesting non-uniform collapse of the cloud. The observations indicate that periodic shock-emissions from acoustically driven cavitation clouds provide a source for the cavitation subharmonic signal, and that shock structure may be used to study intra-cloud dynamics at sub-microsecond timescales.

Acoustic cavitation can occur in therapeutic applications of high-amplitude focused ultrasound. Studying acoustic cavitation has been challenging, because the onset of nucleation is unpredictable. We hypothesized that acoustic cavitation can be forced to occur at a specific location using a laser to nucleate a microcavity in a pre-established ultrasound field. In this paper we describe a scientific instrument that is dedicated to this outcome, combining a focused ultrasound transducer with a pulsed laser. We present high-speed photographic observations of laser-induced cavitation and laser-nucleated acoustic cavitation, at frame rates of 0.5×10(6) frames per second, from laser pulses of energy above and below the optical breakdown threshold, respectively. Acoustic recordings demonstrated inertial cavitation can be controllably introduced to the ultrasound focus. This technique will contribute to the understanding of cavitation evolution in focused ultrasound including for potential therapeutic applications.

Purpose: Varicose veins are a common pathology that can be treated by endovenous thermal procedures like radiofrequency ablation (RFA). Such catheter-based techniques consist in raising the temperature of the vein wall to 70 to 120 C to induce vein wall coagulation. Although effective, this treatment option is not suited for all types of veins and can be technically challenging. Materials and methods: In this study, we used High-Intensity Focused Ultrasound (HIFU) as a noninvasive thermal ablation procedure to treat varicose veins and we assessed the long-term efficacy and safety of the procedure in a sheep model. In vivo experiments were first conducted on two saphenous veins to measure the temperature rise induced at the vein wall during HIFU ablation and were compared with reported RFA-induced thermal rise. Thermocouples were inserted in situ to perform 20 measurements during 8-s ultrasound pulses at 3 MHz. Eighteen saphenous veins of nine anesthetized sheep (2-2.5 % Isoflurane) were then exposed to similar pulses (85 W acoustic, 8 s). After treatments, animals recovered from anesthesia and were followed up 30, 60 and 90 days post-treatment (n ¼ 3 animals per group). At the end of the follow-up, vein segments and perivenous tissues were harvested and histologically examined. Results: Temperatures induced by HIFU pulses were found to be comparable to reported RFA treatments. Likewise, histological findings were similar to the ones reported after RFA and laser-based coagulation necrosis of the vein wall, thrombotic occlusions and vein wall fibrosis. Conclusion: These results support strongly the effectiveness and safety of HIFU for ablating non-invasively veins.

Venous insufficiency is a common disease arising when veins of the lower limb become incompetent. A conventional surgical strategy consists in stripping the incompetent veins. However, this treatment option is invasive and carries complication risks. In the present study, we propose noninvasive high-intensity focused ultrasound (HIFU) to treat lower limbs venous insufficiency, in particular incompetent perforating veins (mean diameter between 2-6 mm). Sonication parameters were designed by numerical simulations using the k-Wave toolbox to ensure continuous coagulation of a vein with a diameter superior or equal to 2 mm. The selected ultrasound exposures were 4 seconds pulses in continuous wave mode. Two types of sonication were studied: (1) fixed pulses and (2) moving pulses at constant speed (0.75 mm.s-1) across the vein. The potential of these exposures to thermally occlude veins were investigated in vivo on rabbit saphenous veins. The impact of vein compression during ultrasonic exposure was also investigated. Fifteen rabbits were used in these trials. A total of 27 saphenous veins (mean diameter 2.0 ± 0.6 mm) were sonicated with a transducer operated at 3 MHz. After a mean 15 days follow-up, rabbits were euthanized and venous samples were extracted and sent for histologic assessment. Only samples with the vein within the HIFU lesion were considered for analysis. Simulated thermal damage distribution demonstrated that fixed pulses and moving pulses respectively placed every 1.5 and 0.5 mm along the vein and delivered at an acoustic power of 85 W and for 4 seconds were able to induce continuous thermal damages along the vein segments. Experimentally, both treatment parameters (1) and (2) have proven effective to occlude veins with a success rate of 82%. Occlusion was always observed when compression was applied. Our results demonstrate that HIFU can durably and non-invasively occlude veins of diameters comparable to human veins.