Transcranial Focused Ultrasound Modifies Disease Progression in SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis
Zhongqiu Hong, Shasha Yi, Miaoqin Deng, Yongsheng Zhong, Yun Zhao, Lili Li, Hui Zhou, Yang Xiao, Xiquan Hu, Lili Niu
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2025 · 10.1109/tuffc.2024.3525143
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressively worsening neurodegenerative condition with very few treatment options available. Ultrasound neuromodulation offers promising benefits for treating neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. However, the effects and underlying mechanisms of ultrasound neuromodulation on ALS remain unclear. A head-mounted ultrasound neuromodulation system was developed to noninvasively stimulate the motor cortex of symptomatic mice carrying the G93A human SOD1 mutation (SOD $1^{\text {G93A}}$ ) for four weeks. Motor performance was assessed through the rotarod locomotor test, grip strength test, and open field test. In addition, the effect of ultrasound stimulation on the elastic modulus of gastrocnemius muscle atrophy was measured using real-time shear wave elastography (SWE). Subsequently, the brain tissues of the mice were harvested. Gastrocnemius morphology was examined using hematoxylin-eosin and Gomori aldehyde-fuchsin (GAF) staining. The number of neurons and the phenotype of microglia in the motor cortex were observed by immunohistochemical analysis. Ultrasound therapy delayed disease onset by 10.7% and increased the lifespan by 6.7% in SOD $1^{\text {G93A}}$ mice by reduction of neuronal loss and enhancement of M2 microglia in the motor cortex. Furthermore, we found significant improvements in motor function for ultrasound-treated mice. More importantly, ultrasound stimulation ameliorated gastrocnemius muscle atrophy in the SOD $1^{\text {G93A}}$ mice. These results revealed the neuroprotective effects of ultrasound against the disease pathogenesis of SOD $1^{\text {G93A}}$ mice. Transcranial ultrasound neuromodulation provides an innovative tool for the intervention and treatment of neurodegenerative diseases.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS to left motor cortex
Target: primary motor cortex — “left motor cortex”
Device: custom-built · wearable single-element focused PZT-8 transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 800 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 6 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 319 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 3.5 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
PRF 100 Hz, duty cycle 10%, stimulation time 6 s, tone-burst length 1 ms; 20 min per session every other day, three sessions per week for four weeks.
Flags from extraction
n_subjects— LIPUS group n = 16 (SOD1 G93A); WT c-Fos experiment n = 4 per group (Fig. 2 legend); total not stated.exposures[0].in_situ.pressure_kpa— Negative peak acoustic pressure 0.319 MPa measured by hydrophone after the mouse skull (Fig. 1); peak negative rather than amplitude.exposures[0].timing.sonication_duration_s— Stated as 'stimulation time of 6 s' within 20-min sessions with an interstimulus interval shown in Fig. 1(b) only.conditions— ALS has no vocabulary entry; recorded as other. Healthy WT mice used for c-Fos experiment.exposures[0].device.family— Transducer described only as PZT-8, Beijing, China; recorded as custom_built.sham_type— Sham mice wore the transducer without ultrasound treatment.