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Spinal cord neuromodulation for blood pressure control using low-intensity focused ultrasound

Angelica F. Lopez, Denis Routkevitch, Patrick J. Kramer, Neil A. Babu, Ritvik Jillala, Ananya Tandri, Zoe Soulé, Emily C. Baca, A. Daniel Davidar, Vikas N. Vattipally, Pierce L. Perkins, Siddharth Krishnan, Ryan S. Bohluli, Charles G. Eberhart, Betty M. Tyler, Nicholas Theodore, Nitish V. Thakor, Amir Manbachi

Scientific Reports 2025 · 10.1038/s41598-025-25330-8

rodentlarge animalhealthyautonomic physiologyhistology molecular

Abstract

Focused ultrasound (FUS) is an innovative technology that delivers angled acoustic energy to a small target region. Previous FUS technology has demonstrated efficacy in applications such as tumor destruction, nerve modulation, and drug delivery in the brain. We investigated the effects of low-intensity FUS (LIFU) stimulation on the spinal cord and its ability to regulate mean arterial pressure (MAP). We found that LIFU stimulation on exposed rat spinal cord could modulate MAP, causing a decrease when applied at a lower thoracic level and an increase when applied at a lumbosacral level. We also found that shorter stimulation periods (30 s) were more effective in inducing a decrease in MAP than more extended stimulation periods (90 s). The time required to return to baseline for MAP was shown to increase with subsequent periods of FUS stimulation. FUS could enable non-pharmacological, spatially targeted MAP control, especially for impaired patients. Future applications of FUS neuromodulation extend into solutions for clinical blood pressure disorders, such as autonomic dysreflexia or chronic hypertension.

Abstract via europepmc.

Speciesrat (Sprague-Dawley); pig (Yorkshire)
Subjects8, 1swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsautonomic physiology, histology molecular — Mean arterial pressure from femoral arterial catheter; heart-rate variability (Poincare plots); H&E histology of spinal cord
Direction of effectbidirectionalMAP decreased with lower thoracic stimulation (mostly 30 s periods) and increased with lumbosacral stimulation; 65% of pig stimulations produced no change in blood pressure.
Adverse eventsobservedIn the pig, lower-intensity stimulation left the cord intact with mild vessel dilation, while higher-intensity stimulation produced subarachnoid haemorrhage, vessel dilatation and degeneration with ablative changes. Long-term safety not explored.

Exposures

Exposure 1: Lower thoracic spinal cord (T11-T13), rat and pig

Target: thoracic spinal cord — “lower thoracic spinal cord (T11-T13)”
Device: Sonic Concepts · Sonic Concepts · H-107 ✓

Pulse timing
Waveformpulsed, continuous
Fundamental frequency (kHz)500✓✓✓⚑
Pulse duration (ms)1, 2,000swept✓✓✓⚑
Pulse repetition frequency (Hz)not reported⚑
Duty cycle (%)1, 5, 10, 15, 20, 25, 50, 100swept✓✓✓⚑
Sonication duration (s)15, 30, 60, 90swept✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)180✓✓✓⚑
Free-field Isppa (W/cm²)1.19✓✓✓⚑
Free-field Ispta (W/cm²)0.01, 0.06, 0.119, 0.12, 0.18, 0.24, 0.3, 0.6, 1.19swept✓✓✓
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Parameters varied per stimulation: amplitude (100-500 mVpp), stimulation period (15, 30, 60 or 90 s), duty cycle (1-100%) and pulse duration (1 or 2000 ms; listed as 0 at 100% duty cycle). Stimulation periods alternated with washout periods over several hours per rat, order randomised within each rat. The single pig received 100-500 mVpp at 1-100% duty cycle (LIFU 100-250 mVpp, 1-30%; HIFU 500 mVpp, 50-100%) at upper and lower thoracic levels.

Exposure 2: Lumbosacral spinal cord (L5-S1), rat

Target: lumbar spinal cord — “lumbosacral spinal cord (L5-S1)”
Device: Sonic Concepts · Sonic Concepts · H-107 ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)1✓✓✓
Pulse repetition frequency (Hz)not reported⚑
Duty cycle (%)1, 5, 10, 15, 20, 25swept✓✓✓⚑
Sonication duration (s)30, 60, 90swept✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)180✓✓✓
Free-field Isppa (W/cm²)1.19✓✓✓⚑
Free-field Ispta (W/cm²)0.01, 0.06, 0.12, 0.18, 0.24, 0.3swept✓✓✓
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

250 mVpp at stimulation periods of 30, 60 or 90 s with duty cycle 1-25% and 1 ms pulse duration (Table 5); stimulation periods alternated with washout periods over several hours per rat, order randomised within each rat.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — Table 4 lists pulse durations of 0 (100% duty cycle), 1 and 2000 ms; at 1 ms pulses the stated duty cycles imply PRFs from 10 to 500 Hz, and 2000 ms at 50% duty cycle implies 0.25 Hz. No PRF is stated; the quote shows only one row of a sweep.
  • exposures[0].timing.pulse_repetition_frequency_hz — PRF not stated anywhere; only duty cycle and pulse duration are given.
  • exposures[1].timing.pulse_repetition_frequency_hz — PRF not stated anywhere.
  • exposures[0].timing.duty_cycle_pct — List of duty cycles read from Table 4; the quote is a sentence naming only 50% and 100%.
  • exposures[1].timing.duty_cycle_pct — List of duty cycles read from Table 5; the quote is one table row only.
  • exposures[1].timing.sonication_duration_s — Table 5 rows show 30, 60 and 90 s; the quote is the table caption giving the shared 15 to 90 s span.
  • exposures[0].free_field.pressure_kpa — Table 1 gives PNP as -0.18 MPa (hydrophone scan); recorded as magnitude, 180 kPa. Amplitude setting for the hydrophone scan is not stated (Fig. 1 simulation used 250 mVpp).
  • exposures[0].free_field.isppa_w_cm2 — Isppa of 1.19 W/cm2 is a transducer hydrophone-scan value (Table 1); the amplitude setting it belongs to is not stated, and the same value is the Ispta at 100% duty cycle in Table 4.
  • exposures[1].free_field.isppa_w_cm2 — Same Table 1 transducer value as exposure 0; not tied to a stated amplitude. Lumbosacral runs used 250 mVpp and duty cycles of 25% or less.
  • exposures[0].unspecified_domain.ispta_w_cm2 — Ispta per parameter set from Table 4 (min and max); the paper does not say whether these are in water or in tissue.
  • exposures[1].unspecified_domain.ispta_w_cm2 — Ispta per parameter set from Table 5 (min and max); domain not stated.
  • exposures[0].timing.waveform — Rows with duty cycle 100% are continuous; others are pulsed.
  • n_subjects — 8 rats and 1 pig; the pig was thoracic only. Rats were split 4 thoracic and 4 lumbosacral.
  • direction_of_effect — Outcome is mean arterial pressure, not neural activity: decreased at thoracic level, increased at lumbosacral level; authors hypothesise neuronal inhibition at both.
  • exposures[0].target.terms — Exposed rat spinal cord after laminectomy; pig had upper and lower thoracic laminectomies; higher-intensity pig exposures produced ablative changes.
  • exposures[0].fundamental_frequency_khz — Centre frequency 500 kHz; the probe's bandwidth is stated as 321 to 708 kHz.