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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