Cavitation-based third ventriculostomy using MRI-guided focused ultrasound

Laboratory investigation

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Object

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.

Methods

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.

Results

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.

Conclusions

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.

Abbreviations used in this paper:ETV = endoscopic third ventriculostomy; MRIgFUS = MRI-guided focused ultrasound.

Article Information

Address correspondence to: Ryan Alkins, M.D., Sunnybrook Research Institute, 2075 Bayview Ave., C713, Toronto, ON, Canada M4N 3M5. email: ralkins@sri.utoronto.ca.

Please include this information when citing this paper: published online September 27, 2013; DOI: 10.3171/2013.8.JNS13969.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    A: A sagittal MRI localizer obtained in the animal after positioning in the in-house fabricated fixture and 30-cm, 1024-element treatment array. The third ventricle floor was positioned as close as possible to the geometrical focus. B: The temperature elevation as measured by MR thermometry, processed by the InSightec treatment software. Prior to starting treatment sonications, the focal position was verified by sonicating at a low power to slightly heat the ultrasound focus and match the focus to that in the MR space. C: The degassed ex vivo human skull is shown secured horizontally to an in-house manufactured polycarbonate holder. The ExAblate 4000 hemispherical array was removed from its usual mount, positioned horizontally on a custom bed, and filled with degassed water prior to animal positioning.

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    A: The position of the 2 hydrophones is highlighted within the treatment array by the dashed circles. These were used to record acoustic emissions during all treatments. B: The acoustic emissions recorded during the third ventriculostomy with the 230-kHz system are displayed, with strong half-harmonic and broadband emissions. The presence of broadband emissions confirms the presence of inertial cavitation during the treatment. C: The temporal resolution of the cavitation detection system during a pulsed sonication was sufficient to capture the pulses. Three consecutive 300-msec pulses (pulse repetition frequency = 1 second) are seen to produce strong half-harmonic emissions in this unsuccessful treatment. Broadband emissions were also detected but at lower amplitudes.

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    Assessment of the treatment effects by T2-weighted MRI using an 8-channel head coil. A: Axial MR image showing the successful transcranial third ventriculostomy performed with the 230-kHz ExAblate system. The sonicated region is identified by the arrow in each plane. There is a rim of low signal intensity around the ventriculostomy, likely due to a small amount of fresh clot, improving visualization of the cavity. The scale bars are incremented every 1 cm. B: Coronal image through the ventriculostomy. C: Sagittal view through the ventriculostomy.

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    Gross sections of the treated brains with the 650-kHz system. A: The resultant ventriculostomy obtained with a peak rarefaction pressure of 15.7 MPa and 100-msec continuous sonication, measuring just over 2 mm. A small amount of clot can be seen at the site. B: The same lesion after cutting of the brain into 5-mm coronal slices. The blood from panel A can be seen in the third ventricle. C: The much larger ventriculostomy generated with a peak rarefaction pressure of 28.8 MPa for 1 second. The ventriculostomy is almost 9 mm in cross-sectional diameter and is free of any debris. D: The corresponding coronal view depicts the empty, smooth-walled cavity.

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    A: Off-target tissue injury is highlighted by the dashed circles in both hemispheres. Microhemorrhages can be seen at the superficial interface of the gray and subcortical white matter. B: The lumens of the damaged vessels can be identified in the centers of the microhemorrhages. This tissue damage identified in the near field is thought to result from multiple high-power sonications, where cavitation nuclei are generated within the near field on previous sonications.

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    Histological sections of the successful ventriculostomies. A: The large ventriculostomy generated with the 650-kHz ExAblate system shown in Fig. 4C and D. There is very fine tissue fractionation and a very sharply demarcated wall. B: In the magnified view, a few small vessels are seen adjacent to the ventriculostomy with extravasated erythrocytes. These occur not more than 1.5 mm from the rim of the cavity. C: The ventriculostomy performed with the 230-kHz system has a significantly different appearance. The tissue fractionation is coarser, with more hemorrhage and larger tissue fragments seen within the cavity. D: In the magnified view, there is a more obvious rim (< 1 mm) of pale tissue around the cavity. Vascular injury was noted up to 3.2 mm from the cavity wall at this frequency (Table 1). In porcine subjects there is unavoidable collateral injury due to the narrow width of the third ventricle, but in humans, where the ventricle is 5–6 mm in width, the focal region could fit entirely within the ventricle, likely without injury to the walls.

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