Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound

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.

Neuromodulation with transcranial focused ultrasound

“…Besides transient effects, FUS applied for a substantial time period (> 10 seconds) can induce long-term changes in neural activity of the stimulated circuits. 8,59 The mechanisms underlying such lasting effects are not understood. In addition to its intrinsic neurostimulatory potential, the effects of FUS can be enhanced or further controlled using nanoparticles that contain a specific neuromodulatory drug of interest.…”

“…If FUS is applied for periods of > 10 seconds, it can induce long-term changes in the neural activity of target circuits. 8,59 This mode of operation has the potential for disrupting aberrant patterns of neural activity in a lasting manner. This may enable noninvasive treatments of brain disorders.…”

“…First, long-term FUS stimulation of the target may induce lasting changes in the stimulated circuits, 8 which may help to alleviate certain signs. Second, it is possible to increase the stimulation intensity by > 2 orders of magnitude and in this way to ablate the target.…”

Volumetric analysis of magnetic resonance–guided focused ultrasound thalamotomy lesions

“…24 These low-intensity focused ultrasound sonications, which create no histological damage and have no MR thermometry heat signature (i.e., do not cause heating), are able to stimulate neural tissue and generate somatosensory evoked potentials when targeting the ventral posterolateral nucleus in an animal model. 5 This technique might eventually be used to functionally map the Vim and surrounding structures without contributing to thermal dosing.…”

Thalamic Deep Brain Stimulation Salvages Failed Focused Ultrasound Thalamotomy for Essential Tremor: A Case Report

“…The FUS procedure relies on intraoperative symptom monitoring to assure proper targeting. Development of FUS-mediated neuromodulation could further improve lesion targeting [15, 16]. …”