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Low-Energy Transcranial Navigation-Guided Focused Ultrasound for Neuropathic Pain: An Exploratory Study

Dong Hoon Shin, Seong Son, Eun Young Kim

Brain Sciences 2023, 13, 1433 · 10.3390/brainsci13101433

human patientchronic painclinical scaleother mri

Abstract

Neuromodulation using high-energy focused ultrasound (FUS) has recently been developed for various neurological disorders, including tremors, epilepsy, and neuropathic pain. We investigated the safety and efficacy of low-energy FUS for patients with chronic neuropathic pain. We conducted a prospective single-arm trial with 3-month follow-up using new transcranial, navigation-guided, focused ultrasound (tcNgFUS) technology to stimulate the anterior cingulate cortex. Eleven patients underwent FUS with a frequency of 250 kHz and spatial-peak temporal-average intensity of 0.72 W/cm 2 . A clinical survey based on the visual analog scale of pain and a brief pain inventory (BPI) was performed during the study period. The average age was 60.55 ± 13.18 years-old with a male-to-female ratio of 6:5. The median current pain decreased from 10.0 to 7.0 ( p = 0.021), median average pain decreased from 8.5 to 6.0 ( p = 0.027), and median maximum pain decreased from 10.0 to 8.0 ( p = 0.008) at 4 weeks after treatment. Additionally, the sum of daily life interference based on BPI was improved from 59.00 ± 11.66 to 51.91 ± 9.18 ( p = 0.021). There were no side effects such as burns, headaches, or seizures, and no significant changes in follow-up brain magnetic resonance imaging. Low-energy tcNgFUS could be a safe and noninvasive neuromodulation technique for the treatment of chronic neuropathic pain.

Abstract via europepmc.

Specieshuman
Subjects11 participants
Sessions per subject6
Randomisedno
Blindingnone
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsclinical scale, other mriVisual analog scale (VAS) for current/average/maximum pain; Korean Brief Pain Inventory (K-BPI); follow-up brain MRI for safety
Direction of effectinhibitoryLow-energy tcNgFUS to the bilateral dorsal ACC was associated with reduced current, average, and maximum pain VAS scores and improved BPI daily-life interference over 4 weeks; direction is inferred from clinical pain reduction, not a direct neurophysiological measurement.
Adverse eventsnone observedNo procedure-related complications, such as a burning sensation of the scalp, headache, or seizure, were observed during the follow-up period. Additionally, no specific changes in the structure of the target, such as inertial cavitation, edema, or hemorrhage, were observed after sonication according to the follow-up brain MRI.

Exposures

Exposure 1: tcNgFUS to bilateral anterior cingulate cortex (Brodmann area 24, dorsal ACC)

Target: dorsal anterior cingulate cortex — “bilateral anterior cingulate cortex (Brodmann area 24, dorsal ACC)
Device: Neurosona · Neurosona Corporation · NS-US100

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)250✓✓
Pulse duration (ms)5, 10swept✓✓
Pulse repetition frequency (Hz)not reported
Duty cycle (%)50, 70swept✓✓
Sonication duration (s)not reported
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Ispta, domain unspecified (W/cm²)0.72✓✓
Protocol, in the paper’s words

Low-energy FUS had a frequency of 250 kHz, spatial-peak temporal-average intensity of less than 0.72 W/cm2, and tone burst duration of 5–10 ms. Stimulation was performed with a 50–70% duty cycle (the rate occupied by an ultrasonic donation per second). The total stimulation time, including the rest period, did not exceed 30 min in all patients. Additionally, the device was used within a range that does not exceed a Mechanical Index of 1.9 (in situ peak rarefaction pressure less than 0.95 MPa according to the Food and Drug Administration safety standards for ultrasonic imaging devices). Treatment was carried out three times a week for 2 weeks.

Flags from extraction

  • n_subjects12 patients enrolled/recruited; 1 withdrew consent during follow-up leaving 11 in the final analysis. n_subjects reported here is the enrolled/treated total (12); flagged because analysed n=11.
  • n_sessions_per_subjectPaper states frequency (3x/week for 2 weeks) rather than a single total session count; 6 is derived by simple multiplication of the stated schedule.
  • exposures[0].timing.pulse_repetition_frequency_hzPRF is not numerically stated; only tone-burst duration and duty cycle are given, and duty-cycle/PRF cannot be used to resolve pulse duration since pulse duration is already directly stated as a range.
  • exposures[0].unspecified_domain.pressure_kpaPaper states the device was operated 'within a range that does not exceed... in situ peak rarefaction pressure less than 0.95 MPa' – this is a stated safety ceiling/compliance limit, not necessarily the actual delivered pressure, so no specific pressure value was recorded.
  • exposures[0].unspecified_domain.ispta_w_cm2Intensity of 0.72 W/cm2 (abstract) / 'less than 0.72 W/cm2' (Methods) is not explicitly assigned to a free-field or in-situ domain.