Device for Multifocal Delivery of Ultrasound Into Deep Brain Regions in Humans
Thomas Riis, Daniel Feldman, Adam Losser, Brian Mickey, Jan Kubanek
IEEE Transactions on Biomedical Engineering 2024, 71, 660-668 · 10.1109/tbme.2023.3313987
Abstract
Low-intensity focused ultrasound provides the means to noninvasively stimulate or release drugs in specified deep brain targets. However, successful clinical translations require hardware that maximizes acoustic transmission through the skull, enables flexible electronic steering, and provides accurate and reproducible targeting while minimizing the use of MRI. We have developed a device that addresses these practical requirements. The device delivers ultrasound through the temporal and parietal skull windows, which minimize the attenuation and distortions of the ultrasound by the skull. The device consists of 252 independently controlled elements, which provides the ability to modulate multiple deep brain targets at a high spatiotemporal resolution, without the need to move the device or the subject. And finally, the device uses a mechanical registration method that enables accurate deep brain targeting both inside and outside of the MRI. Using this method, a single MRI scan is necessary for accurate targeting; repeated subsequent treatments can be performed reproducibly in an MRI-free manner. We validated these functions by transiently modulating specific deep brain regions in two patients with treatment-resistant depression.
Abstract via europepmc.
Exposures
Exposure 1: Subgenual cingulate cortex (SGC) stimulation
Target: subgenual anterior cingulate cortex — “subgenual cingulate cortex (SGC)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | ⚑ |
| Duty cycle (%) | 0.75 | ✓✓✓ |
| Sonication duration (s) | 60, 180swept | ✓✓✓ |
| 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) | 1,000 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 31 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.233 | ✓✓✓ |
Ultrasound was delivered into the target in 30 ms ON periods followed by 4 s OFF periods; sonication duration varied from 60-180 s. Targets were presented randomly in a blinded manner, interleaved with an active sham (unfocused plane wave with the same energy and waveform) over a 1.5 hour neuromodulation session; a psychiatrist rated mood immediately after each of 27 total stimuli.
Exposure 2: Ventral striatum stimulation
Target: nucleus accumbens — “ventral striatum”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | 0.75 | ✓✓✓ |
| Sonication duration (s) | 60, 180swept | ✓✓✓ |
| 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) | 1,000 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 31 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.233 | ✓✓✓ |
Ultrasound was delivered into the target in 30 ms ON periods followed by 4 s OFF periods; sonication duration varied from 60-180 s. Targets were presented randomly in a blinded manner, interleaved with an active sham (unfocused plane wave with the same energy and waveform) over a 1.5 hour neuromodulation session.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Paper gives 30 ms ON and 4 s OFF periods and a duty cycle (0.75%) but never labels a PRF value; computing PRF from the ON+OFF period would require summing two separately stated numbers, which is arithmetic this extraction avoids.sham_type— Active sham delivered the same energy/waveform as an unfocused (defocused) plane wave rather than a powered-off transducer or a different anatomical site, which does not cleanly match a listed sham_type category.direction_of_effect— Direction is based on the authors' stated intent to suppress SGC activity via low duty cycle and the resulting mood improvement; no direct neural activity measurement (e.g., imaging) confirmed inhibition in this paper.n_subjects— Only 2 patients were studied; findings are proof-of-concept.