Neurogenic Flare Response following Image-Guided Focused Ultrasound in the Mouse Peripheral Nervous System in Vivo
Min Gon Kim, Hermes A.S. Kamimura, Elisa E. Konofagou
Ultrasound in Medicine & Biology 2021, 47, 2759-2767 · 10.1016/j.ultrasmedbio.2021.04.030
Abstract
Focused ultrasound (FUS) has been used to non-invasively elicit or inhibit motor neuronal activity in the mouse peripheral nervous system in vivo. However, less is known about whether FUS elicits immune system responses associated with peripheral sensory neuronal activity. In this study, we sought to determine that non-invasive ultrasound image-guided FUS can elicit the neurogenic axon reflex of peripheral nerves in the mouse sciatic nerve. The local vasodilation in the plantar view of the hind paw detected with a high-resolution laser Doppler imager indicated neurogenic flare responses after FUS stimulation. The effects of FUS were compared with control groups, where a distinct pattern of blood flow changes was observed only in FUS-elicited neurogenic flare responses. The findings indicate that image-guided FUS elicits local axon reflexes in vivo with a high degree of specificity and penetration depth.
Abstract via europepmc.
Exposures
Exposure 1: FUS stimulation of the distal sciatic nerve
Target: sciatic nerve — “distal sciatic nerve”
Device: Sonic Concepts · Sonic Concepts, Inc. · H-108 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,100 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 10% | |
| Sonication duration (s) | 180, 600swept | ✓✓✓ |
| 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 | |
| Pressure, domain unspecified (kPa) | 1,960 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 71 | ✓✓✓⚑ |
FUS with a peak positive/negative pressure of 1.96/1.95 MPa, pulse duration of 1 ms, PRF of 100 Hz, and total sonication time of 10 min was applied to the distal sciatic nerve to elicit an acute flare reaction (n = 8 hind limbs of mice). In addition, FUS with a total sonication time of 3 min (n = 2 hindlimbs of mice) was separately conducted, producing a similar blood-flow pattern. Based on a previous study, short-/high-intensity FUS (Isppa 6-610 W/cm2) was applied to activate motor neurons for a targeting procedure, and long-/low-intensity FUS (Isppa = 71 W/cm2, MI = 1.1) was applied to activate sensory neurons for the neurogenic-inflammation experiments; full pulse timing for the high-intensity targeting sonication is not given in this paper.
Flags from extraction
n_subjects— Total 'exposed to ultrasound' is not stated; group sizes for FUS conditions (on-target 10 min n=8, off-target n=6, 20-dB attenuated 'noise' condition n=6, FUS 3-min n=2) are listed rather than summed. Units are 'hind limbs of mice', which may not equal distinct animals.exposures[0].unspecified_domain.pressure_kpa— Domain (free field vs in situ) of the 1.96/1.95 MPa peak positive/negative pressure is not stated; recorded as unspecified_domain. Value given as separate positive/negative peaks; the positive peak (1.96 MPa) is recorded.exposures[0].unspecified_domain.isppa_w_cm2— Domain of the Isppa=71 W/cm2 value is not stated by the paper; recorded as unspecified_domain. A separate high-intensity regime (Isppa 6-610 W/cm2) used for a targeting procedure (from a prior study) is described only qualitatively here without matching pulse timing, so it is not included as a numeric field value.