Image-guided low-intensity focused ultrasound neuromodulation: acoustic targeting optimization and functional validation in a reward circuit model
Sudeep Mondal, Hao Yang, Danielle Gulick, Richard Czuma, Shixie Jiang, Huabei Jiang
Brain Stimulation 2026 · 10.1016/j.brs.2026.103190
Abstract
Objective To develop and validate an ultrasound-guided low-intensity focused ultrasound (USg-LIFU) platform for subject-specific deep-brain neuromodulation and test whether ventral tegmental area (VTA) targeting modulates alcohol-related behaviour in a mouse model of alcohol use disorder. Methods USg-LIFU uses ultrasound tomography (UT)-assisted acoustic velocity mapping and subject-specific finite element method (FEM) simulations to incorporate reconstructed acoustic-property information into FEM-based focal prediction and guide mechanical alignment of the predicted focal zone toward the target. Targeting accuracy is verified ex-vivo using high-intensity focused ultrasound (HIFU) to create thermal lesions in mouse brain tissue. In-vivo neuromodulatory effects were tested in cHAP mice (n=10) that underwent six USg-LIFU sessions targeting the VTA on alternating days and compared with sham controls (n=5). Daily measures were recorded to assess alcohol and water intake, and blood alcohol concentration (BAC) was assessed before, during, and after treatment. Results Simulations showed that changes in brain acoustic velocity shifted focal position and altered pressure distribution, underscoring the need for subject-specific correction. Ex-vivo studies demonstrated that the optimized focus converged on the predefined intracranial target, with visible thermal damage at the intended location after sonication. In-vivo, most LIFU-treated mice showed reduced ethanol intake and increased water consumption after treatment initiation, whereas sham animals maintained or strengthened alcohol preference. Across the treatment period, mean alcohol intake decreased by approximately 51% in the treated group, consistent with reductions in BAC measurements. Conclusion USg-LIFU achieved accurate subject-specific targeting and produced measurable modulation of alcohol-related behaviour, supporting its potential as an accessible platform for non-invasive deep-brain neuromodulation.
Abstract via europepmc.
Exposures
Exposure 1: USg-LIFU of the VTA in cHAP mice
Target: ventral tegmental area — “ventral tegmental area (VTA)”
Device: Sonic Concepts · Sonic Concepts · H101 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,300 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 15 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reportedsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 0.168 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.084 | ✓✓✓ |
Pulsed sonication with pulse duration 0.5 ms and PRF 1 kHz (50% duty cycle), 15 s per session, six sessions on alternating days (days 15 to 25), delivered after UT-FEM guided mechanical alignment under isoflurane.
Flags from extraction
exposures[0].in_situ.method— Paper calls the intensities 'estimated in-situ' (citing ref 35) without saying whether simulated, derated or measured.exposures[0].in_situ.isppa_w_cm2— No pressure reported; intensities only.sham_type— Sham mice had handling, anaesthesia, positioning and coupling but no LIFU; how the no-output condition was produced is not described.exposures[0].label— An ex vivo HIFU lesion experiment and 2D FEM simulations are also reported but give no stimulation parameters and are not recorded as exposures.