Pilot study on the effects of low intensity focused ultrasound in a swine model of neuropathic pain
Abigail Hellman, Teresa Maietta, Alicia Clum, Kanakaharini Byraju, Nataly Raviv, Michael D. Staudt, Erin Jeannotte, Goutam Ghoshal, Damian Shin, Paul Neubauer, Emery Williams, Tamas Heffter, Clif Burdette, Jiang Qian, Julia Nalwalk, Julie G. Pilitsis
Journal of Neurosurgery 2021 · 10.3171/2020.9.jns202962
Abstract
Objective The authors' laboratory has previously demonstrated beneficial effects of noninvasive low intensity focused ultrasound (liFUS), targeted at the dorsal root ganglion (DRG), for reducing allodynia in rodent neuropathic pain models. However, in rats the DRG is 5 mm below the skin when approached laterally, while in humans the DRG is typically 5-8 cm deep. Here, using a modified liFUS probe, the authors demonstrated the feasibility of using external liFUS for modulation of antinociceptive responses in neuropathic swine. Methods Two cohorts of swine underwent a common peroneal nerve injury (CPNI) to induce neuropathic pain. In the first cohort, pigs (14 kg) were iteratively tested to determine treatment parameters. liFUS penetration to the L5 DRG was verified by using a thermocouple to monitor tissue temperature changes and by measuring nerve conduction velocity (NCV) at the corresponding common peroneal nerve (CPN). Pain behaviors were monitored before and after treatment. DRG was evaluated for tissue damage postmortem. Based on data from the first cohort, a treatment algorithm was developed, parameter predictions were verified, and neuropathic pain was significantly modified in a second cohort of larger swine (20 kg). Results The authors performed a dose-response curve analysis in 14-kg CPNI swine. Specifically, after confirming that the liFUS probe could reach 5 cm in ex vivo tissue experiments, the authors tested liFUS in 14-kg CPNI swine. The mean ± SEM DRG depth was 3.79 ± 0.09 cm in this initial cohort. The parameters were determined and then extrapolated to larger animals (20 kg), and predictions were verified. Tissue temperature elevations at the treatment site did not exceed 2°C, and the expected increases in the CPN NCV were observed. liFUS treatment eliminated pain guarding in all animals for the duration of follow-up (up to 1 month) and improved allodynia for 5 days postprocedure. No evidence of histological damage was seen using Fluoro-Jade and H&E staining. Conclusions The results demonstrate that a 5-cm depth can be reached with external liFUS and alters pain behavior and allodynia in a large-animal model of neuropathic pain.
Abstract via europepmc.
Exposures
Exposure 1: liFUS to L5 DRG, 25-30 W
Target: dorsal root ganglion — “L5 DRG”
Device: other named manufacturer · Acoustic MedSystems, Inc. · liFUS array / probe ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 2,475 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 13.1579 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 38 | ✓✓✓⚑ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 180, 240swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | ⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Single treatment of 25-30 W for 3-4 minutes under anaesthesia with a water-cooled array; the optimal dose was 25 W, 2.475 MHz, a pulse of 38 Hz at 50% duty cycle for 3.5 minutes, raised to 28 W in larger animals.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Stated as 'a pulse of 38 Hz'; taken as PRF. Frequency, PRF and duty cycle are for the optimal dose only.exposures[0].free_field.pressure_kpa— Only electrical power (25-30 W) is reported; no pressure or intensity values.exposures[0].device.manufacturer— Maker not named in a sentence about the device; inferred from the authors being Acoustic MedSystems employees and device development credit. The device is described as the authors' own modified array.n_subjects— Two cohorts of 8 and 4 pigs; Table 1 lists only 7 of the 8 in the first cohort. No control group.exposures[0].timing.sonication_duration_s— Range 3-4 min across the dose-response animals (3 min to 4 min in Tables 1 and 3).