Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound

J Neurosurg 128:875–884, 2018

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.

Pulsatile Dynamics of the Optic Nerve Sheath and Intracranial Pressure

ONS and ICP

Neurosurgery 79:100–107, 2016

Raised intracranial pressure (ICP) may lead to increased stiffness of the optic nerve sheath (ONS).

OBJECTIVE: To develop a method for analyzing ONS dynamics from transorbital ultrasound and investigate a potential difference between patients with raised ICP vs normal ICP.

METHODS: We retrospectively analyzed data from 16 patients (#12 years old) for whom ultrasound image sequences of the ONS had been acquired from both eyes just before invasive measurement of ICP. Eight patients had an ICP $20 mm Hg. The transverse motion on each side of the ONS was estimated from ultrasound, and Fourier analysis was used to extract the magnitude of the displacement corresponding to the heart rate. By calculating the normalized absolute difference between the displacements on each side of the ONS, a measure of ONS deformation was obtained. This parameter was referred to as the deformability index. According to our hypothesis, because deformability is inversely related to stiffness, we expected this parameter to be lower for ICP $20 mm Hg compared with ICP ,20 mm Hg. The one-sided Mann-Whitney U test was used for statistical comparison.

RESULTS: The deformability index was significantly lower in the group with ICP $20 mm Hg (median value 0.11 vs 0.24; P = .002).

CONCLUSION: We present a method for assessment of ONS pulsatile dynamics using transorbital ultrasound imaging. A significant difference was noted between the patient groups, indicating that deformability of the ONS may be relevant as a noninvasive marker of raised ICP. The clinical implications are promising and should be investigated in future clinical studies.

Evaluation of the ShuntCheck Noninvasive Thermal Technique for Shunt Flow Detection in Hydrocephalic Patients

Neurosurgery 68:198–205, 2011 DOI: 10.1227/NEU.0b013e3181fe2db6

ShuntCheck (Neuro Diagnostic Devices, Inc., Trevose, Pennsylvania) is a new device designed to detect cerebrospinal fluid (CSF) flow in a shunt by sensing skin temperature downstream from a region of CSF cooled by an ice cube.

OBJECTIVE: To understand its accuracy and utility, we evaluated the use of this device during routine office visits as well as during workup for suspected shunt malfunction.

METHODS: One hundred shunted patients were tested, including 48 evaluated during possible shunt malfunction, of whom 24 went on to surgical exploration. Digitally recorded data were blindly analyzed and compared with surgical findings and clinical follow-up.

RESULTS: Findings in the 20 malfunctioning shunts with unambiguous flow or absence of flow at surgery were strongly correlated with ShuntCheck results (sensitivity and specificity to flow of 80% and 100%, respectively, P = .0007, Fisher’s exact test, measure of agreement k = 0.8). However, the thermal determination did not distinguish patients in the suspected malfunction group who received surgery from those who were discharged without surgery (P = .248 by Fisher’s exact test, k = 0.20). Half of the patients seen in routine office visits did not have detectable flow, although none required shunt revision on clinical grounds. Intermittent flow was specifically demonstrated in one subject who had multiple flow determinations.

CONCLUSION: Operative findings show that the technique is sensitive and specific for detecting flow, but failure to detect flow does not statistically predict the need for surgery. A better understanding of the normal dynamics of flow in individual patients, which this device may yield, will be necessary before the true clinical utility of noninvasive flow measurement can be assessed.