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Elastic, anisotropic tissue such as tendon has proven resistant to mechanical fractionation by histotripsy, a subset of focused ultrasound that uses the creation, oscillation and collapse of cavitation bubbles to fractionate tissue. Our objective was to fabricate an optically transparent hydrogel that mimics tendon for evaluation of histotripsy bubble dynamics. Ex vivo bovine deep digital flexor tendons were obtained (n = 4), and varying formulations of polyacrylamide (PA), collagen and fibrin hydrogels (n = 3 each) were fabricated. Axial sound speeds were measured at 1 MHz for calculation of anisotropy. All samples were treated with a 1.5-MHz focused ultrasound transducer with 10-ms pulses repeated at 1 Hz (p +  = 127 MPa, p -  = 35 MPa); treatments were monitored with passive cavitation imaging and high-speed photography. Dehydrated fibrin gels were found to be the most similar to tendon in cavitation emission energy (fibrin = 0.69 ± 0.24, tendon = 0.64 ± 0.19 [× 10 10 V 2 ]) and anisotropy (fibrin = 3.16 ± 1.12, tendon = 19.4). Bubble cloud area in dehydrated fibrin (0.79 ± 0.14 mm 2 ) was significantly smaller than most other tested hydrogels. Finally, anisotropy was found to have moderately strong linear relationships with cavitation energy and bubble cloud size (r = -0.65 and -0.80, respectively). Dehydrated fibrin shows potential as a repeatable, transparent, tissue-mimicking hydrogel for evaluation of histotripsy bubble dynamics in elastic, anisotropic tissues., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The color Doppler ultrasound twinkling artifact is a rapid color shift that appears on 43%-96% of kidney stones. Surface microbubbles on kidney stones are theorized to cause twinkling as exposure to elevated static pressures of 0.41-1.13 MPa (approximately 0.5-1 times diagnostic ultrasound pressure and 5-10 times ambient pressure) reduced twinkling. However, it is unclear what external and internal stone features support bubbles. Thirteen ex vivo kidney stones were scanned with color Doppler ultrasound at 2.5, 5 and 18.5 MHz. Select stones were imaged with environmental scanning electron microscopy or underwater micro-computed tomography to evaluate features that may cause twinkling. Results revealed that the lower frequencies produced larger volumes of twinkling. Condensation first occurred in the smallest (∼1 µm diameter) surface pores and may be indicative of where bubbles form. Gas pockets were seen inside two of three tested stones that may contribute to twinkling. Overall, these results provide evidence of cavity structures both externally and internally and their correlation to the twinkling artifact. This indicates that microbubbles may be present on and within kidney stones and may contribute to the twinkling artifact., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The color Doppler ultrasound twinkling artifact has been found to improve detection of kidney stones with ultrasound; however, it appears on only ∼60% of stones. Evidence from ex vivo kidney stones suggests twinkling arises from microbubbles stabilized in crevices on the stone surface. Yet it is unknown whether these bubbles are present on stones in humans. Here, we used a research ultrasound system to quantify twinkling in humans with kidney stones in a hyperbaric chamber. Eight human patients with non-obstructive kidney stones previously observed to twinkle were exposed to a maximum pressure of 4 atmospheres absolute (ATA) while breathing air, except during the 10-min pause at 1.6 ATA and while the pressure decreased to 1 ATA, during which patients breathed oxygen to minimize the risk of decompression sickness. A paired one-way t-test was used to compare the mean twinkle power at each pressure pause with baseline twinkling, with p < 0.05 considered to indicate significance. Results revealed that exposure to 3 and 4 ATA of pressure significantly reduced twinkle power by averages of 35% and 39%, respectively, in 7 patients (p = 0.04); data from the eighth patient were excluded because of corruption. This study supports the theory that microbubbles are present on kidney stones in humans., Competing Interests: Conflict of interest disclosure Michael R. Bailey, Barbrina Dunmire and Bryan W. Cunitz have equity in and consult for SonoMotion, Inc., which has licensed technology related to kidney stone imaging from the University of Washington., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Bone demineralization, dehydration and stasis put astronauts at increased risk of forming kidney stones in space. The color-Doppler ultrasound "twinkling artifact," which highlights kidney stones with color, can make stones readily detectable with ultrasound; however, our previous results suggest twinkling is caused by microbubbles on the stone surface which could be affected by the elevated levels of carbon dioxide found on space vehicles. Four pigs were implanted with kidney stones and imaged with ultrasound while the anesthetic carrier gas oscillated between oxygen and air containing 0.8% carbon dioxide. On exposure of the pigs to 0.8% carbon dioxide, twinkling was significantly reduced after 9-25 min and recovered when the carrier gas returned to oxygen. These trends repeated when pigs were again exposed to 0.8% carbon dioxide followed by oxygen. The reduction of twinkling caused by exposure to elevated carbon dioxide may make kidney stone detection with twinkling difficult in current space vehicles., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Ultrasonic atomization, or the emission of a fog of droplets, was recently proposed to explain tissue fractionation in boiling histotripsy. However, even though liquid atomization has been studied extensively, the mechanisms underlying tissue atomization remain unclear. In the work described here, high-speed photography and overpressure were used to evaluate the role of bubbles in tissue atomization. As static pressure increased, the degree of fractionation decreased, and the ex vivo tissue became thermally denatured. The effect of surface wetness on atomization was also evaluated in vivo and in tissue-mimicking gels, where surface wetness was found to enhance atomization by forming surface instabilities that augment cavitation. In addition, experimental results indicated that wetting collagenous tissues, such as the liver capsule, allowed atomization to breach such barriers. These results highlight the importance of bubbles and surface instabilities in atomization and could be used to enhance boiling histotripsy for transition to clinical use., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)