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Around 30 million tendon injuries occur annually in the U.S. costing $\$ $ 114 billion. Conservative therapies, like dry needling, promote healing in chronically injured tendons by inducing microdamage but have mixed success rates. Focused ultrasound (fUS) therapy can noninvasively fractionate tissues through the creation, oscillation, and collapse of bubbles in a process termed histotripsy; however, highly collagenous tissues, like tendon, have shown resistance to mechanical fractionation. This study histologically evaluates whether fUS mechanical disruption is achievable in tendons. Ex vivo rat tendons (45 Achilles and 44 supraspinatus) were exposed to 1.5-MHz fUS operating with 0.1–10 ms pulses repeated at 1–100 Hz for 15–60 s with peak positive pressures <89 MPa and peak negative pressures <26 MPa; other tendons were exposed to dry needling or sham. Immediately after treatment, tendons were flash-frozen and stained with hematoxylin and eosin (H&E) or alpha-nicotinamide adenine dinucleotide diaphorase ($\alpha $ -NADH-d) and evaluated by two reviewers blinded to the exposure conditions. Results showed successful creation of bubbles for all fUS-treated samples; however, not all samples showed histological injury. When the injury was detected, parameter sets with shorter pulses (0.1–1 ms), lower acoustic pressures, or reduced treatment times showed mechanical disruption in the form of fiber separation and fraying with little to no thermal injury. Longer pulses or treatment times showed a combination of mechanical and thermal injury. These findings suggest that mechanical disruption is achievable in tendons within a small window of acoustic parameters, supporting the potential of fUS therapy in tendon treatment. [ABSTRACT FROM AUTHOR]

Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 5–30 pulses of 1–10 ms duration per focus, 1% duty cycle, peak acoustic powers 0.9–3.8 kW, sonication foci spaced 1–1.5 mm apart in a rectangular grid with 5–15 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: A noninvasive tool to reposition kidney stones could have significant impact in the management of stone disease. Our research group has developed a noninvasive transcutaneous ultrasound device. A review and update of the current status of this technology is provided. Discussion of Technology: Stone propulsion is achieved through short bursts of focused, ultrasonic pulses. The initial system consisted of an eight-element annular array transducer, computer, and separate ultrasound imager. In the current generation, imaging and therapy are completed with one ultrasound system and a commercial probe. This generation allows real-time ultrasound imaging, targeting, and propulsion. Safety and effectiveness for the relocation of calyceal stones have been demonstrated in the porcine model. Role in Endourology: This technology may have applications in repositioning stones as an adjunct to lithotripsy, facilitating clearance of residual fragments after lithotripsy, expelling de novo stones, and potentially repositioning obstructing stones. Human trials are in preparation. [ABSTRACT FROM AUTHOR]

Atomization and fountain formation is a well-known phenomenon that occurs when a focused ultrasound wave in liquid encounters an air interface. High intensity focused ultrasound (HIFU) has been shown to fractionate a tissue into submicron-sized fragments in a process termed boiling histotripsy, wherein the focused ultrasound wave superheats the tissue at the focus, producing a millimetre-sized boiling or vapour bubble in several milliseconds. Yet the question of how this millimetre-sized boiling bubble creates submicronsized tissue fragments remains. The hypothesis of this work is that the tissue can behave as a liquid such that it atomizes and forms a fountain within the vapour bubble produced in boiling histotripsy. We describe an experiment, in which a 2 MHz HIFU transducer (maximum in situ intensity of 24 000 W cm-2) was aligned with an air-tissue interface meant to simulate the boiling bubble. Atomization and fountain formation was observed with highspeed photography and resulted in tissue erosion. Histological examination of the atomized tissue showed whole and fragmented cells and nuclei. Air- liquid interfaces were also filmed. Our conclusion was that HIFU can fountain and atomize tissue. Although this process does not entirely mimic what was observed in liquids, it does explain many aspects of tissue fractionation in boiling histotripsy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To provide an update on a research device to ultrasonically reposition kidney stones transcutaneously. This article reports preclinical safety and effectiveness studies, survival data, modifications of the system, and testing in a stone-forming porcine model. These data formed the basis for regulatory approval to test the device in humans. Materials and Methods The ultrasound burst was shortened to 50 ms from previous investigations with 1-s bursts. Focused ultrasound was used to expel 2- to 5-mm calcium oxalate monohydrate stones placed ureteroscopically in 5 pigs. Additionally, de novo stones were imaged and repositioned in a stone-forming porcine model. Acute safety studies were performed targeting 2 kidneys (6 sites) and 3 pancreases (8 sites). Survival studies followed 10 animals for 1 week after simulated treatment. Serum and urine analyses were performed, and tissues were evaluated histologically. Results All ureteroscopically implanted stones (6/6) were repositioned out of the kidney in 14 ± 8 minutes with 13 ± 6 bursts. On average, 3 bursts moved a stone more than 4 mm and collectively accounted for the majority of relocation. Stones (3 mm) were detected and repositioned in the 200-kg stone-forming model. No injury was detected in the acute or survival studies. Conclusion Ultrasonic propulsion is safe and effective in the porcine model. Stones were expelled from the kidney. De novo stones formed in a large porcine model were repositioned. No adverse effects were identified with the acute studies directly targeting kidney or pancreatic tissue or during the survival studies indicating no evidence of delayed tissue injury. [ABSTRACT FROM AUTHOR]

Tendon injuries are extremely common, resulting in mechanically weaker tendons that could lead to tendon rupture. Dry needling (DN) is widely used to manage pain and function after injury. However, DN is invasive and high inter-practitioner variability has led to mixed success rates. Focused ultrasound (fUS) is a non-invasive medical technology that directs ultrasound energy into a well-defined focal volume. fUS can induce thermal ablation or mechanical fractionation, with bioeffect type controlled through ultrasound parameters. Tendons must withstand high physiological loads, thus treatments maintaining tendon mechanical properties while promoting healing are needed. Our objective was to evaluate mechanical effects of DN and 3 fUS parameter sets, chosen to prioritize mechanical fractionation, on Achilles and supraspinatus tendons. Ex vivo rat Achilles and supraspinatus tendons (50 each) were divided into sham, DN, fUS-1, fUS-2, and fUS-3 (n = 10/group). Following treatment, tendons were mechanically tested. Elastic modulus of supraspinatus tendons treated with DN (126.64 ± 28.1 MPa) was lower than sham (153.02 ± 29.3 MPa; p = 0.0280). Stiffness and percent relaxation of tendons treated with DN (Achilles: 114.40 ± 31.6 N/mm; 49.10 ± 6.1%; supraspinatus: 109.53 ± 30.8 N/mm; 50.17 ± 7.6%) were lower (all p < 0.0334) than sham (Achilles: 141.34 ± 20.9 N/mm; 60.30 ± 7.7%; supraspinatus: 135.14 ± 30.2 N/mm; 60.85 ± 15.4%). Modulus of Achilles and supraspinatus tendons treated with fUS-1 (159.88 ± 25.7 MPa; 150.12 ± 22.0 MPa, respectively) were similar to sham (156.35 ± 23.0 MPa; 153.02 ± 29.3 MPa, respectively). These results suggest that fUS preserves mechanical properties better than DN, with fUS-1 performing better than fUS-2 and fUS-3. fUS should be studied further to fully understand its mechanical and healing effects to help evaluate fUS as an alternative, non-invasive treatment for tendon injuries. [ABSTRACT FROM AUTHOR]

In the U.S., approximately 14 million tendon and ligament injuries are reported each year. Dry needling (DN) is a conservative treatment introduced to alleviate pain and restore function; however, it is invasive and has mixed success. Focused ultrasound (fUS) is a non-invasive technology that directs ultrasound energy into a well-defined focal volume. fUS induces thermal and/or mechanical bioeffects which can be controlled by the choice of ultrasound parameters. fUS could be an alternative to DN for treatment of tendon injuries, but the bioeffects must be established. Thus, the purpose of this pilot study was to compare the effect of DN and fUS on the mechanical properties and cell morphology of 30 ex vivo rat Achilles tendons. Tendons were randomly assigned to sham, DN, or fUS, with 10 tendons per group. Within each group, 5 tendons were evaluated mechanically, and 5 tendons were analyzed histologically. Elastic modulus in the DN (74.05 ± 15.0 MPa) group was significantly lower than sham (149.84 ± 59.1 MPa; p = 0.0094) and fUS (128.84 ± 28.3 MPa; p = 0.0453) groups. Stiffness in DN (329.05 ± 236.8 N/mm; p = 0.0034) and fUS (315.26 ± 68.9 N/mm; p = 0.0027) groups were significantly lower than sham (786.10 ± 238.7 N/mm) group. Histologically, localized necrosis was observed in 3 out of 5 tendons exposed to fUS, with surrounding tissue unharmed; no evidence of cellular injury was observed in DN or sham groups. These results suggest that fUS preserves the mechanical properties of tendon better than DN. Further studies are needed to evaluate fUS as an alternative, noninvasive treatment modality for tendon injuries. [ABSTRACT FROM AUTHOR]