A wearable spiral ultrasound patch for focused ultrasound peripheral neuromodulation of diabetic neuropathic pain

Cong Pu, Ben Fu, Pengda Lu, Xin Guan, Jiayi Zhang, Yuting Shen, Xiao Li, Lehang Guo, Huixiong Xu, Xiaoning Jiang, Chang Peng

Cell Reports Physical Science 2025 · 10.1016/j.xcrp.2025.102684

rodentchronic painotherbehaviourinvasive electrophysiologyhistology molecular

Speciesrat (Sprague-Dawley)

Subjects6, 6swept animals

Sessions per subject1, 14swept

Randomisedyes

Blindingnot reported

Sham / controlundescribed, no treatment control

Auditory controlnot reported

Readout timingoffline

Anaesthesiaanaesthetised

Readoutsbehaviour, invasive electrophysiology, histology molecular — Von Frey paw withdrawal threshold; hot-plate paw withdrawal latency; sciatic nerve compound action potential conduction velocity; H&E staining of sciatic nerve; wound closure; PC12 live/dead staining

Direction of effectmixed or unclearAfter 14 daily sessions the multiple-treatment group had higher paw withdrawal threshold and latency than the sham and control groups; nerve conduction velocity was higher than in the multiple-sham group but lower than in the untreated control group. A single session had no significant effect.

Adverse eventsnone observedH&E staining of sciatic nerve showed no apparent damage and PC12 cell viability was unchanged after up to 30 min of exposure; skin temperature on a human forearm rose 0.3 to 0.4 degC over 5 min.

Exposures

Exposure 1: w-SUP 1.5 MHz pulsed thermal stimulation of the sciatic nerve

Target: sciatic nerve — “sciatic nerve”
Device: custom-built · wearable spiral ultrasound patch (w-SUP), 41-element PZT-4 phyllotaxis array, driven via Verasonics Vantage HIFU system and a Keysight 33500B generator with AF Instrumentation 100A400A amplifier ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	1,500	✓✓✓
Pulse duration (ms)	0.0133	✓✓✓⚑
Pulse repetition frequency (Hz)	not reported	⚑
Duty cycle (%)	80	✓✓✓
Sonication duration (s)	300	✓✓✓⚑

Pressure and intensity, by domain
Free-field pressure (kPa)	450	✓✓✓
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)	0.357	✓✓✓
In-situ Ispta (W/cm²)	0.277	✓✓✓

Protocol, in the paper’s words

Waveform generator set at 1.5 MHz, 600 mVpp, 20 burst cycles and an 80% duty cycle, with the amplifier at 80% gain; a 5-min session once a day, single session on day 1 for the ST group and daily from day 1 to day 14 for the MT group.

Flags from extraction

n_subjects — 30 rats were enrolled in five groups of 6; only the ST and MT groups (6 each) were sonicated, so the group sizes are listed.
n_sessions_per_subject — ST group received one session, MT group 14 daily sessions.
exposures[0].unspecified_domain.isppa_w_cm2 — Isppa and Ispta (357 and 277 mW/cm2) are given in the Discussion without a domain; the Methods equations include an FDA attenuation factor, so the values may be derated.
exposures[0].timing.pulse_duration_ms — Pulse structure given as 20 cycles and 80% duty cycle; no PRF or pulse duration stated.
exposures[0].timing.pulse_repetition_frequency_hz — No PRF stated for the treatment sequence.
exposures[0].timing.sonication_duration_s — 5 min stated as minutes; converted to 300 s.
sham_type — SS and MS groups are described only as not stimulated by ultrasound; whether a patch was applied is not stated. A separate untreated control group existed.
blinding — Behaviour was video-recorded 'to ensure a blind experimental design' but blinding of the experimenters is not otherwise described.
model_system — PC12 cells and pork tissue were also exposed in safety and thermal tests; only the rat exposure is recorded.

Notes: Peripheral thermal neuromodulation; the in-vivo exposure targets the sciatic nerve under ultrasound guidance.