The effects of various exposures (intensity, duration) of high-intensity focused ultrasound (HIFU) on sciatic nerve conduction were investigated in vivo in rats. The objective was to identify HIFU exposures that produce biological effects ranging from partial to complete conduction block, indicating potential use of HIFU as an alternative to current clinical methods of inducing nerve conduction block. In the study, 26 nerves were exposed and treated with 5-s applications of 5.7-MHZ HIFU with acoustic intensities of 390, 2,255, 3,310, and 7,890 W/cm(2) (spatial peak, temporal peak). Compound muscle action potentials (CMAPs), in response to electrical stimulation of the nerve proximal to the HIFU site, were recorded from the plantar foot muscles immediately before and after HIFU treatment and 2 and 4 h after treatment. Furthermore, a preliminary long-term investigation was performed on 27 nerves with the same four sets of HIFU parameters. CMAPs were measured at the survival endpoint for each animal (7 or 28 days after treatment). For nerves treated with the three lower exposures, CMAPs decreased initially within 4 h or 7 days after HIFU treatment and then recovered to their baseline level at 28 days after treatment. For the highest exposure, however, CMAPs remained absent even 28 days after treatment. These exposure-dependent effects of HIFU on nerve function suggest its future potential as a novel treatment for severe spasticity and pain.

The objective of our work has been to investigate the use of ultrasound image-guided high-intensity focused ultrasound (HIFU) to non-invasively produce conduction block in rabbit sciatic nerves in vivo, a technique that could become a treatment of spasticity and pain. The work reported here involved the investigation of the duration of such conduction blocks after HIFU treatment and whether they resulted in axon degeneration. The right sciatic nerves of 12 rabbits were treated, under guidance of ultrasound imaging, with repeated 5-s applications of 3.2 MHz HIFU with in situ intensity of 1930 W/cm(2) (spatial-average, temporal-average) until conduction block was achieved. Survival endpoints were 0, 7, or 14 days after HIFU treatment, at which point the nerve conduction was assessed. Qualitative and quantitative histological analysis of nerve sections proximal and distal to the HIFU site was performed. Conduction block of all 12 nerves was achieved with average HIFU treatment time of 10.5+/-4.9 s (mean+/-SD). The volume of necrosis of adjacent muscle was measured to be 1.59+/-1.1 cm(3) (mean+/-SD). For all nerves, conduction block remained at the survival endpoint and the block resulted in degeneration of axons distal to the HIFU site, as confirmed by electrophysiological and histological methods. Potential clinical applications include treatment of spasticity in patients with spinal cord injury or pain in cancer patients.

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Safety concerns exist for potential thermal damage at tissue-air or tissue-bone interfaces located in the post-focal region during high intensity focused ultrasound (HIFU) treatments. We tested the feasibility of reducing thermal energy deposited at the post-focal tissue-air interfaces by producing bubbles (due to acoustic cavitation and/or boiling) at the HIFU focus. HIFU (in-situ intensities of 460-3500 W/cm2, frequencies of 3.2-5.5 MHz) was applied for 30 s to produce lesions (in turkey breast in-vitro (n = 37), and rabbit liver (n = 4) and thigh muscle in-vivo (n = 11)). Tissue temperature was measured at the tissue-air interface using a thermal (infrared) camera. Ultrasound imaging was used to detect bubbles at the HIFU focus, appearing as a hyperechoic region. In-vitro results showed that when no bubbles were present at the focus (at lower intensities of 460-850 W/cm2), the temperature at the interface increased continuously, up to 7.3 +/- 4.0 degrees C above the baseline by the end of treatment. When bubbles formed immediately after the start of HIFU treatment (at the high intensity of 3360 W/cm2), the temperature increased briefly for 3.5 s to 7.4 +/- 3.6 degrees C above the baseline temperature and then decreased to 4.0 +/- 1.4 degrees C above the baseline by the end of treatment. Similar results were obtained in in-vivo experiments with the temperature increases (above the baseline temperature) at the muscle-air and liver-air interfaces at the end of the high intensity treatment lower by 7.1 degrees C and 6.0 degrees C, respectively, as compared to the low intensity treatment. Thermal effects of HIFU at post-focal tissue-air interfaces, such as in bowels, could result in clinically significant increases in temperature. Bubble formation at the HIFU focus may provide a method for shielding the post-focal region from potential thermal damage.

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The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significant growth, particularly over the past decade. The eventual widespread clinical adoption of this non-invasive therapeutic modality require continued progress, in a multitude of activities including technical, pre-clinical, and clinical research, regulatory approval and reimbursement, manufacturer growth, and other commercial and public sector investments into the field, all within a multi-stakeholder environment. We present here a snapshot of the field of focused ultrasound and describe how it has progressed over the past several decades. It is assessed using metrics which include quantity and breadth of academic work (presentations, publications), funding trends, manufacturer presence in the field, number of treated patients, number of indications reaching first-in-human status, and quantity and breadth of clinical indications.

Our objective was to evaluate high-intensity focused ultrasound (HIFU) for minimizing blood loss during surgery by hemodynamically isolating large portions of solid organs before their resection. A high-power HIFU device (in situ intensity of 9000 W/cm(2), frequency of 3.3 MHz) was used to produce a wall of cautery for sealing of blood vessels along the resection line in surgically exposed solid organs (liver lobes, spleen and kidneys) of eight adult pigs. Following HIFU application, the distal portion of the organ was excised using a scalpel. If any blood vessels were still bleeding, additional HIFU application was used to stop the bleeding. The resection was achieved in 6.0 +/- 1.5 min (liver), 3.6 +/- 1.1 min (spleen) and 2.8 +/- 0.6 min (kidneys) of HIFU treatment time, with no occurrence of bleeding for up to 4 h (until sacrifice). The coagulated region at the resection line had average width of 3 cm and extended through the whole thickness of the organ (up to 4 cm). Blood vessels of up to 1 cm in size were occluded. This method holds promise for future clinical applications in resection of solid tumors and hemorrhage control from high-grade organ injuries.