Cavitation-based third ventriculostomy using MRI-guided focused ultrasound

Abstract

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.

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

“…Images of bubble activity were obtained starting at pressure levels below the threshold for BBB opening, which is consistent with our previous results obtained without the presence of a human skull. 66 Although the technique was applied during FUS-induced BBB opening in the present work, the method is directly applicable to other cavitation-mediated brain therapies, such as ultrasoundassisted clot lysis, 24,25 tissue fractionation, 26,27 or cavitationenhanced ablation. [101][102][103] Furthermore, the proposed technology could be used to confirm the absence of inertial cavitation during thermal ablation therapies in the brain, in order to avoid hemorrhagic events.…”

“…26,27 In contrast with the thermal-based therapies described above, these treatments rely on mechanical interactions, namely, those of the incident ultrasound field with gas-or vapor-filled microspheres that are either formed via nucleation using high amplitude pulsed ultrasound exposures 28 or injected intravenously in the form of encapsulated microbubbles, long used as contrast agents in diagnostic imaging. 29,30 These procedures are more challenging to monitor online via MR imaging (MRI), in part because the macroscopic temperature rise generated is insignificant.…”

“…29,30 These procedures are more challenging to monitor online via MR imaging (MRI), in part because the macroscopic temperature rise generated is insignificant. 17,26,31 The development of methods to reliably monitor acoustic activity in real-time throughout such nonthermal FUS brain therapies is critical to ensure that the induced cavitation activity and its associated bioeffects are contained within the intended target volume during treatment.…”

The use of transcranial focused ultrasound in CNS diseases

“…В настоящее время применение аппарата разрешено в клинической практике в Европе (CEMark) для проведения таламото-мии при эссенциальном треморе и нейропатической бо-ли. В лабораторных условиях продемонстрирована воз-можность использования данного аппарата также для де-струкции посредством эффекта кавитации, а также для локального увеличения проницаемости гематоэнцефали-ческого барьера (ГЭБ) [16,17].…”

“…Alkins и соавт. [17] представили исследование, вы-полненное на свиньях, по проведению 3-вентрикулосто-мии с помощью ФУЗ под контролем МРТ. Для проведе-ния деструкции авторы использовали аппарат ExAblate 4000 с измененными настройками, что позволило иници-ировать в фокусе не нагревание, а эффект нестационар-ной кавитации.…”