Trans-Spinal Focused Ultrasound Stimulation Selectively Modulates Descending Motor Pathway
Evgenii Kim, Jeungeun Kum, Hyungmin Kim
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2022 · 10.1109/tnsre.2022.3148877
Abstract
Compared to current non-invasive methods utilizing magnetic and electrical means, focused ultrasound provides greater spatial resolution and penetration depth. Despite the broad application of ultrasound stimulation, there is a lack of studies dedicated to the investigation of acoustic neuromodulation on the spinal cord. This study aims to apply focused ultrasound on the spinal cord to modulate the descending pathways in a non-invasive fashion. The application of trans-spinal focused ultrasound (tsFUS) was examined on the motor deficit mouse model. tsFUS was achieved using a single-element focused ultrasound transducer operating at 3 MHz. The sonication was performed on anesthetized 6 week-old mice targeting T12 and L3 vertebrae. The effect was analyzed by comparing electromyography responses from the hindlimb induced by electrical stimulation of the motor cortex. Further, the mouse model with the Harmaline-induced essential tremor (ET) was selected to investigate the potential clinical application of tsFUS. The safety was verified by histological assessment. Sonication at the T12 area inhibited motor response, while sonication over the L3 region provided signal enhancement. Sonication of T12 of the ET mouse also showed the ability of ultrasound to suppress tremors. Meanwhile, the histological examination did not show any abnormalities with the highest applied acoustic pressure. In this work, a non-invasive motor signal modulation was achieved using tsFUS. Moreover, the results showed the ability of focused ultrasound to manage tremors in a safe manner. This study provides a stepping stone for the trans-spinal application of focused ultrasound to motor-related disorders.
Abstract via europepmc.
Exposures
Exposure 1: T12 trans-spinal FUS
Target: thoracic spinal cord — “T12 vertebra / spinal cord location”
Device: custom-built · in-house single-element 3 MHz PZT-4 transducer, 6 mm diameter, 3D-printed lens, 10 mm radius of curvature
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | ⚑ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 800, 1,400, 2,200swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 9.9, 28, 76swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | 4.95, 14, 38swept | ✓✓✓ |
| 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 |
Pulse train of 200 ms, 0.5 ms tone bursts at 1 kHz PRF, delivered 1 s before each electrical cortical stimulation, interstimulus interval 2 s; sessions of 100 trials separated by 5 min. For the tremor model, 1 min baseline, 1 min tsFUS at 1.4 MPa on T12, 1 min rest.
Exposure 2: L3 trans-spinal FUS
Target: lumbar spinal cord — “L3 vertebra”
Device: custom-built · in-house single-element 3 MHz PZT-4 transducer, 6 mm diameter, 3D-printed lens, 10 mm radius of curvature
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 1,400, 2,200swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 28, 76swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | 14, 38swept | ✓✓✓ |
| 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 |
Pulse train of 200 ms, 0.5 ms tone bursts at 1 kHz PRF, delivered 1 s before each electrical cortical stimulation, interstimulus interval 2 s; sessions of 100 trials separated by 5 min. For the tremor model, 1 min baseline, 1 min tsFUS at 1.4 MPa on T12, 1 min rest.
Flags from extraction
exposures[0].unspecified_domain.pressure_kpa— Pressures are peak negative pressure in MPa; paper says pressure profiles were measured in free water but does not say the Table I values are free-field, so kept unspecified.exposures[0].timing.duty_cycle_pct— Duty cycle not stated; not computed.n_subjects— 50 mice split across descending (20), ascending (10), tremor (10), histology (5) and supplementary (5) experiments.exposures[0].unspecified_domain.ispta_w_cm2— Table I intensity values are not labelled with a domain.sham_type— No sham group; baseline and recovery periods within animal served as control; histology compared with untreated mice.n_sessions_per_subject— Varies by group (two or three sessions in the descending experiments).