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Cavitation-based third ventriculostomy using MRI-guided focused ultrasound.

Authors: Alkins R, Huang Y, Pajek D, Hynynen K

Transcranial focused ultrasound is increasingly being investigated as a minimally invasive treatment for a range of intracranial pathologies. At higher peak rarefaction pressures than those used for thermal ablation, focused ultrasound can initiate inertial cavitation and create holes in the brain by fractionation of the tissue elements. The authors investigated the technical feasibility of using MRI-guided focused ultrasound to perform a third ventriculostomy as a possible noninvasive alternative to endoscopic third ventriculostomy for hydrocephalus. A craniectomy was performed in male pigs weighing 13-19 kg to expose the supratentorial brain, leaving the dura mater intact. Seven pigs were treated through the craniectomy, while 2 pigs were treated through ex vivo human skulls placed in the beam path. Registration and targeting was done using T2-weighted MRI sequences. For transcranial treatments a CT scan was used to correct the beam from aberrations due to the skull and maintain a small, high-intensity focus. Sonications were performed at both 650 kHz and 230 kHz at a range of intensities, and the in situ pressures were estimated both from simulations and experimental data to establish a threshold for tissue fractionation in the brain. In craniectomized animals at 650 kHz, a peak pressure ≥ 22.7 MPa for 1 second was needed to reliably create a ventriculostomy. Transcranially at this frequency the ExAblate 4000 was unable to generate the required intensity to fractionate tissue, although cavitation was initiated. At 230 kHz, ventriculostomy was successful through the skull with a peak pressure of 8.8 MPa. This is the first study to suggest that it is possible to perform a completely noninvasive third ventriculostomy using ultrasound. This may pave the way for future studies and eventually provide an alternative means for the creation of CSF communications in the brain, including perforation of the septum pellucidum or intraventricular membranes.

Introduction

Purpose Histotripsy
Study Objective To evaluate the technical feasibility of using MRI-guided focused ultrasound to perform a noninvasive third ventriculostomy for hydrocephalus.
Animal model / Human subject Pig (Sus scrofa domesticus), strain None, age None, male; weight 13–19 kg
Disease model Hydrocephalus
MRI or image guidance method T2-weighted MRI sequences for registration and targeting (MRI-guided); CT scans used for transcranial treatments to correct skull-induced beam aberrations
Targeted brain region(s) third ventricle

Outcomes and Safety

Summary of Outcomes Focused ultrasound produced tissue fractionation enabling a third ventriculostomy in pigs; with a craniectomy at 650 kHz a peak pressure ≥22.7 MPa for 1 s was required to reliably create the ventriculostomy, while transcranial treatment succeeded at 230 kHz with a peak pressure of 8.8 MPa (the system could not reach the 650 kHz transcranial threshold, though cavitation was observed).
Duration of biological effect 1 second
Safety-related matter No adverse effects or safety complications are reported; the paper notes cavitation was initiated transcranially at 650 kHz without tissue fractionation and successful ventriculostomy at 230 kHz, but does not describe any injuries or other safety issues.

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate 4000
FUS Frequency 650 kHz, 230 kHz
FUS Pressure ≥22.7 MPa (peak, 1 s) ; 8.8 MPa (peak)
Pulse duration 1 second
Duration of a single FUS session 1 second
Focal Characteristics focal depth: None; focal length: None; aperture size: None
Treatment frequency Multiple sessions

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