Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound
Robert F. Dallapiazza, Kelsie F. Timbie, Stephen Holmberg, Jeremy Gatesman, M. Beatriz Lopes, Richard J. Price, G. Wilson Miller, W. Jeffrey Elias
Journal of Neurosurgery 2018, 128, 875-884 · 10.3171/2016.11.jns16976
Abstract
OBJECTIVE Ultrasound can be precisely focused through the intact human skull to target deep regions of the brain for stereotactic ablations. Acoustic energy at much lower intensities is capable of both exciting and inhibiting neural tissues without causing tissue heating or damage. The objective of this study was to demonstrate the effects of low-intensity focused ultrasound (LIFU) for neuromodulation and selective mapping in the thalamus of a large-brain animal. METHODS Ten Yorkshire swine ( Sus scrofa domesticus) were used in this study. In the first neuromodulation experiment, the lemniscal sensory thalamus was stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs) were monitored. In a second mapping experiment, the ventromedial and ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU, while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the acoustic focus was assessed using MR thermography. At the end of the experiments, all tissues were assessed histologically for damage. RESULTS LIFU targeted to the ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% ± 11.4% (mean ± SD) compared with baseline recordings. Second, we found a similar degree of inhibition with a high spatial resolution (∼ 2 mm) since adjacent thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus could be inhibited without affecting the ventrolateral nucleus. During MR thermography imaging, there was no observed tissue heating during LIFU sonications and no histological evidence of tissue damage. CONCLUSIONS These results suggest that LIFU can be safely used to modulate neuronal circuits in the central nervous system and that noninvasive brain mapping with focused ultrasound may be feasible in humans.
Abstract via europepmc.
Exposures
Exposure 1: LIFU of right ventroposterolateral thalamic nucleus (VPL)
Target: ventral posterolateral nucleus — “ventroposterolateral thalamic nucleus (VPL)”
Device: not reported · FUS Instruments, Inc. (1.14 MHz); InSightec (650/220 kHz) · RK-100 (1.14 MHz); ExAblate Neuro (650 kHz and 220 kHz phased arrays) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,140, 650, 220swept | ✓✓✓⚑ |
| Pulse duration (ms) | 43.7 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 43.7pulse duration × PRF gives 43.7% | ✓✓✓ |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 25, 30swept | ✓✓✓⚑ |
Ultrasound experiments at 1.14 MHz used a preclinical single-element FUS system; experiments at 650(710) kHz and 220 kHz used the clinical ExAblate Neuro (InSightec) phased-array systems, with the same duty cycle and sonication duration maintained across all three systems. Off-target control sonications (2 mm anterior to VPM) and contralateral control sonications (left VPL) were also performed as anatomical specificity controls. HIFU sonications (continuous-wave, 20 W, 20 s) were used separately to verify targeting/thermometry and to create ablative lesions for comparison, not as a neuromodulation exposure.
Exposure 2: LIFU of right ventroposteromedial thalamic nucleus (VPM)
Target: ventral posteromedial nucleus — “ventroposteromedial thalamic nucleus (VPM)”
Device: not reported · FUS Instruments, Inc. (1.14 MHz); InSightec (650/220 kHz) · RK-100 (1.14 MHz); ExAblate Neuro (650 kHz and 220 kHz phased arrays) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,140, 650, 220swept | ✓✓✓ |
| Pulse duration (ms) | 43.7 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 43.7pulse duration × PRF gives 43.7% | ✓✓✓ |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 25, 30swept | ✓✓✓ |
Ultrasound experiments at 1.14 MHz used a preclinical single-element FUS system; experiments at 650(710) kHz and 220 kHz used the clinical ExAblate Neuro (InSightec) phased-array systems, with the same duty cycle and sonication duration maintained across all three systems. Off-target control sonications (2 mm anterior to VPM) and contralateral control sonications (left VPL) were also performed as anatomical specificity controls. HIFU sonications (continuous-wave, 20 W, 20 s) were used separately to verify targeting/thermometry and to create ablative lesions for comparison, not as a neuromodulation exposure.
Flags from extraction
n_subjects— N=10 is stated for the combined histology cohort (8 LIFU + 6 HIFU, overlapping); different sub-experiments (e.g., N=4 animals for thalamic mapping) report different subject counts, and no single 'total subjects in study' sentence is given.exposures[0].fundamental_frequency_khz— Paper is internally inconsistent about the clinical transducer frequency: the Methods section header says 'Clinical 710 and 220 kHz FUS systems' while the same paragraph and Figure 1 caption say '650 kHz'; both target VPL and VPM are reported to have been tested across all three transducers with the same intensity/duty-cycle protocol, but outcome percentages in Fig. 3 are not broken down by frequency.exposures[0].device— Different devices (custom 1.14 MHz single-element system vs. clinical InSightec ExAblate Neuro at 650/220 kHz) were used across the frequency list within this single exposure entry; a single device object cannot fully represent this.exposures[0].unspecified_domain.isppa_w_cm2— Paper reports this value as 'ISA' (spatial-average intensity), not explicitly Isppa or Ispta, and does not state whether it is a free-field or in-situ value.