Jessica L. Foley

Effects of high-intensity focused ultrasound on nerve conduction

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/cm2 (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. Muscle Nerve, 2007

Prevention of post-focal thermal damage by formation of bubbles at the focus during high intensity focused ultrasound therapy

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.

Selective reduction of multifetal pregnancy using high-intensity focused ultrasound in the rabbit model

High‐order multifetal pregnancies carry a significant risk of obstetric complications and poor pregnancy outcome. Selective reduction has traditionally been performed using transabdominal and transvaginal ultrasound‐guided intracardiac injection of potassium chloride. We have previously shown that high‐intensity focused ultrasound (HIFU) can create a coagulative tissue necrosis in the sheep fetus. The objective of this study was to investigate the feasibility of non‐invasive selective fetal reduction using HIFU in a rabbit model.

Ultrasound-guided HIFU neurolysis of peripheral nerves to treat spasticity and pain

Spasticity, a major complication of disorders of the central nervous system (CNS) signified by uncontrollable muscle contractions, is difficult to treat effectively. We report on the use of ultrasound image-guided high-intensity focused ultrasound (HIFU) to target and suppress the function of the sciatic nerve of rabbits in vivo as a possible treatment of spasticity and pain. The image-guided HIFU device included a 3.2 MHz spherically curved transducer (focal dimensions of 5.1 mm/spl times/0.76 mm) integrated with an intraoperative imaging probe (CL10-5, Philips HDI-1000), such that the HIFU focus was within the image plane. The sciatic nerve was imaged in cross-section and identified between two muscle planes, and the HIFU treatment was directed to the nerve and monitored in real time. In situ focal acoustic intensity of 1480-1850 W/cm/sup 2/ was applied using a scanning method (scan rate of 0.5-0.6 mm/s). The force response of the plantarflexion muscles in the rabbit foot to electrical stimulation of the sciatic nerve was measured both before and after HIFU treatment using a force gauge perpendicularly coupled to the metatarsal joint of the rabbit foot. The force response was approximately 0.55 N before HIFU treatment, and complete suppression of this force was achieved after HIFU treatment, indicating complete conduction block. HIFU treatment time of 36/spl plusmn/14 s (mean /spl plusmn/ standard deviation) was effective in achieving complete conduction block in 100% of the 22 nerves treated (11 rabbits). Gross examination showed blanching of the nerves at the HIFU treatment site and lesion volumes of 2.8/spl plusmn/1.4 cm/sup 2/ encompassing the nerves. Histologic results indicated axonal demyelination and necrosis of Schwann cells as probable mechanisms of nerve block. With accurate localization and targeting of peripheral nerves using ultrasound imaging, HIFU could become a promising tool for the suppression of spasticity and pain.

High throughput high intensity focused ultrasound (HIFU) treatment for tissue necrosis

To increase HIFU throughput, a HIFU transducer (diameter of 7 cm, focal length of 6 cm, operating frequency of 3.4 MHz), coupled to an imaging probe (ICT 7‐4, Sonosite), was driven by 100 W driving unit with 500 W amplifier. A water pillow connected to a circulation pump with degassed water provided transducer coupling and cooling. Input electrical power was 400 W, corresponding to focal intensity of 51 300 W/cm2 (in water). HIFU was applied transcutaneously in porcine thigh muscle in vivo, and intraoperatively in liver hilum, for 30–60 s. After 30 s of treatment, muscle lesions had diameter of 2.1±0.4 cm and length of 2.0±0.4 cm. After 60 s of treatment, muscle lesions had diameter of 3.1±0.9 cm and length of 3.1±1.0 cm. In few cases of severe skin burns, the lesions were formed immediately under the skin and were shallow (∼1 cm). Liver lesions had diameter of 2.1±0.3 cm and length of 2.3±0.6 cm. In comparison, after the 30 s treatment with our standard HIFU device (focal intensity of 27 000 W/cm2,...

Ultrasound‐guided high frequency focused ultrasound neurolysis of peripheral nerves to treat spasticity and pain

Spasticity, a complication of central nervous system disorders, signified by uncontrollable muscle contractions, is difficult to treat effectively. The use of ultrasound image‐guided high‐intensity focused ultrasound (HIFU) to target and suppress the function of the sciatic nerve of rabbits in vivo, as a possible treatment of spasticity and pain, will be presented. The image‐guided HIFU device included a 3.2‐MHz spherically‐curved transducer and an intraoperative imaging probe. A focal intensity of 1480−1850 W/cm2 was effective in achieving complete conduction block in 100% of 22 nerves with HIFU treatment times of 36±14 s (mean±SD). Gross examination showed blanching of the nerve at the treatment site and lesion volumes of 2.8±1.4 cm3 encompassing the nerve. Histological examination indicated axonal demyelination and necrosis of Schwann cells as probable mechanisms of nerve block. Long‐term studies showed that HIFU intensity of 1930 W/cm2, applied to 12 nerves for an average time of 10.5±4.9 s, enabled n...

Ultrasound‐Guided HIFU Neurolysis Of Peripheral Nerves to Treat Spasticity and Pain

Spasticity, a major complication of disorders of the central nervous system (CNS) signified by uncontrollable muscle contractions, is difficult to treat effectively. We report on the use of ultrasound image-guided high-intensity focused ultrasound (HIFU) to target and suppress the function of the sciatic nerve of rabbits in vivo as a possible treatment of spasticity and pain. The image-guided HIFU device included a 3.2 MHz spherically curved transducer (focal dimensions of 5.1 mm/spl times/0.76 mm) integrated with an intraoperative imaging probe (CL10-5, Philips HDI-1000), such that the HIFU focus was within the image plane. The sciatic nerve was imaged in cross-section and identified between two muscle planes, and the HIFU treatment was directed to the nerve and monitored in real time. In situ focal acoustic intensity of 1480-1850 W/cm/sup 2/ was applied using a scanning method (scan rate of 0.5-0.6 mm/s). The force response of the plantarflexion muscles in the rabbit foot to electrical stimulation of the sciatic nerve was measured both before and after HIFU treatment using a force gauge perpendicularly coupled to the metatarsal joint of the rabbit foot. The force response was approximately 0.55 N before HIFU treatment, and complete suppression of this force was achieved after HIFU treatment, indicating complete conduction block. HIFU treatment time of 36/spl plusmn/14 s (mean /spl plusmn/ standard deviation) was effective in achieving complete conduction block in 100% of the 22 nerves treated (11 rabbits). Gross examination showed blanching of the nerves at the HIFU treatment site and lesion volumes of 2.8/spl plusmn/1.4 cm/sup 2/ encompassing the nerves. Histologic results indicated axonal demyelination and necrosis of Schwann cells as probable mechanisms of nerve block. With accurate localization and targeting of peripheral nerves using ultrasound imaging, HIFU could become a promising tool for the suppression of spasticity and pain.