Focused Ultrasound Platform for Investigating Therapeutic Neuromodulation Across the Human Hippocampus
Spencer T. Brinker, Frank Preiswerk, Phillip J. White, Timothy Y. Mariano, Nathan J. McDannold, Ellen J. Bubrick
Ultrasound in Medicine & Biology 2020 · 10.1016/j.ultrasmedbio.2020.01.007
Abstract
Pulsed low-intensity focused ultrasound (PLIFUS) has shown promise in inducing neuromodulation in several animal and human studies. Therefore, it is of clinical interest to develop experimental platforms to test repetitive PLIFUS as a therapeutic modality in humans with neurologic disorders. In the study described here, our aim was to develop a laboratory-built experimental device platform intended to deliver repetitive PLIFUS across the hippocampus in seizure onset zones of patients with drug-resistant temporal lobe epilepsy. The system uses neuronavigation targeting over multiple therapeutic sessions. PLIFUS (548 kHz) was emitted across multiple hippocampal targets in a human subject with temporal lobe epilepsy using a mechanically steered piezoelectric transducer. Stimulation was delivered up to 2.25 W/cm 2 spatial peak temporal average intensity (free-field equivalent), with 36%-50% duty cycle, 500-ms sonications and 7-s inter-stimulation intervals lasting 140 s per target and repeated for multiple sessions. A first-in-human PLIFUS course of treatment was successfully delivered using the device platform with no adverse events.
Abstract via europepmc.
Exposures
Exposure 1: PLIFUS to hippocampal targets (subject 1, TLE)
Target: hippocampus — “human hippocampus (multiple hippocampal targets, seizure onset zone)”
Device: custom-built · Piezo Kinetics · PZT-4, 548 kHz spherically focused piezoceramic transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 548 | ✓✓✓ |
| Pulse duration (ms) | not reported | ⚑ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 36, 50swept | ✓✓✓⚑ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | 140, 320swept | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.5, 2.25swept | ✓✓✓ |
| 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 |
140-s sonications emitted to each hippocampal target with 500-ms sonications repeated with 7-s inter-stimulation intervals, lasting 140 s per target; treatment repeated across multiple hippocampal targets (four targets) and repeated in biweekly therapy sessions for 3 weeks in subject 1 with TLE.
Flags from extraction
exposures[0].free_field.pressure_kpa— Range (0.14-0.32 MPa) and Ispta range (0.5-2.25 W/cm2) are stated only in the Figure 1 caption, not in the Results text (which gives only the maximum, 0.32 MPa / 2.25 W/cm2); recorded here as the full stated range but flagged as figure-legend-sourced.exposures[0].timing.pulse_duration_ms— Only PRF (500 Hz) and duty cycle (36-50%) are stated for the internal pulsing within the 500-ms sonication; no explicit pulse/cycle count is given to state a pulse duration, so left not_reported rather than computed.exposures[0].timing.duty_cycle_pct— Text and figure caption both give duty cycle as "36% 50%"; likely an en-dash lost in OCR representing a 36-50% range across sessions/targets, recorded as [36, 50].n_sessions_per_subject— Paper states treatment was 'repeated in biweekly therapy sessions for 3 weeks' but never gives an explicit session count.