A microsurgical bifurcation rabbit model to investigate the effect of high-intensity focused ultrasound on aneurysms: a technical note
© Coluccia et al.; licensee BioMed Central Ltd. 2014
Received: 18 May 2014
Accepted: 23 September 2014
Published: 31 October 2014
Recent clinical studies confirmed the high potential of MR-guided focused ultrasound (MRgFUS) in the field of functional neurosurgery. While its ability for precise thermo-ablation within soft tissue is widely recognized, the impact of high-intensity focused ultrasound (HIFU) on larger vessels is less explored. We used a bifurcation aneurysm model in rabbits to investigate the possible effects on the walls of vascular aneurysms and to assess the risk and prospect of this procedure for managing neurovascular disorders.
Experimental bifurcation aneurysms were microsurgically created in New Zealand white rabbits and sonicated using MRgFUS.
A temperature of max. 54°C could be achieved close to the aneurysm, and the shape and size of the aneurysm were noticeably changed, as shown by MR angiography.
The presented rabbit model proved suitable and capable of being extended to acquire data on the effect of HIFU on aneurysms and larger vessels. The fact that HIFU led to an alteration of the aneurysm without inducing rupture encourages further investigations.
KeywordsFocused ultrasound Sonication Aneurysm Rabbit model
High-intensity ultrasound focused into a small volume is known to generate heat, which enables precise and non-invasive thermo-coagulation of tissue. Whereas the first attempts to apply this physical phenomenon in clinical use were troubled by a lack of thermometric control and exact guidance of the focal point, today it is possible to combine the delivery of ultrasonic beam with magnetic resonance image guidance, allowing thermometric monitoring and accurate targeting. Phased array transducers and CT-based phase correction allow compensation for wave aberration at the calvaria and targeting of intracranial regions selectively and precisely for ablation. Therefore, MR-guided focused ultrasound (MRgFUS) has been notably successful for non-invasive functional neurosurgery[2, 3]. Focused ultrasound has been shown to be capable not only of ablating soft tissue but also of occluding arteries and controlling bleeding[4, 5], presumably through a combination of a thermal coagulative effect on the vessel wall and mechanically induced blood flow stasis leading to thrombosis. In this technical note, we investigated the usefulness of a microsurgically produced bifurcation aneurysm rabbit model to study the influence and possible risks of MRgFUS on aneurysms in order to assess this innovative technique as an option for future neurovascular procedures.
The study protocol was approved by the Swiss Animal Care and Experimentation Committee (approval number BE 14/10). All aneurysms were created in adult female New Zealand white rabbits (3–4 kg). A detailed description of the aneurysm creation is presented elsewhere. In brief, general anesthesia was induced by administration of ketamine hydrochloride (Pfizer AG, Zurich, Switzerland) and xylazine hydrochloride (Vétoquinol AG, Ittigen, Switzerland) and continued intravenously.
Magnetic resonance-guided focused ultrasound sonication
Due to its capacity for image guidance and precise delivery of ablative heat, MRgFUS is especially interesting in the setting of brain diseases, for which a narrow area of functional anatomy as well as limited intraoperative visual orientation often impairs safe access to lesions. While recent clinical results of MRgFUS in functional neurosurgery for tremor and chronic pain are highly encouraging[2, 3], possible extension of treatment options within the spectrum of brain diseases is desirable. In this respect, an implementation of FUS on structures other than parenchymal tissue has to be considered. In terms of vascular diseases, different reports are available in which FUS is evaluated for revascularization of thrombosed vessels. Furthermore, in animal studies, the application of FUS was also shown for bleeding control in injured arteries or vessel occlusion[5, 4], making FUS a promising procedure to be tested in the treatment of arteriovenous malformations (AVM), cavernomas, or aneurysms. Hynynen et al. were able to occlude a branch of a renal artery in rabbits (approximately 0.6 mm in diameter and 2 cm in depth from the skin surface) using a small transducer of 100-mm diameter operating at 1.5 MHz with peak intensities of up to 6,500 W cm-2. The device used here is optimized for patient treatments at 650 kHz; therefore, variations of animal positioning and sonication scheme were limited. Accordingly, the maximum sonication intensity we could reach was 1,750 W cm-2. One issue when applying FUS in the vicinity of high-perfusion areas is the heat convection by permanent blood flow. Therefore, higher acoustic power will be needed to reach ablative temperatures. Along with the increase of acoustic power comes the elevated risk of inducing cavitation, which can result in unintended tissue damage. In view of the issues mentioned, a drawback of the presented model is the short distance between the aneurysm and the skin, so that standing waves and burns are possible. In addition, the proximity to the air-filled trachea may promote cavitation formation. An alternative to add variability to the sonication scheme is the injection of microbubbles (ultrasonographic contrast agents) into the vascular system, which may enhance the efficacy of the focused ultrasound. By removing the skin from the sonication path, we were able to achieve ablative temperatures, and changes in shape and size of the aneurysms were detectable. Whether this was due to temporary vasospasm, denaturation of the vessel wall, or a combination of effects could not yet be assessed. Currently, additional experiments including digital subtraction angiography follow-up and histological analysis of the vessel wall are ongoing. Taking into account the procedural difficulties encountered, further studies will use larger rabbits (approximately 1-year-old rabbits weighing 5–6 kg) and adapt the surgical method (transposition by abdominal fat pads) in order to have more tissue separating the skin and the aneurysm. Moreover, we will aim at altering the sonication effect by applying microbubbles.
By slowly and moderately increasing thermal energy using MRgFUS, we could show that—despite the heat convection through high blood flow—it is possible to reach ablative temperatures at the aneurysm and to modify its shape without inducing rupture—this being a possible risk brought on by the mechanical effect of ultrasonic beam. Even if aneurysm modification with FUS may not be viable in the near future, it is important to investigate possible interferences, e.g., for the feasibility and risk assessment of patients harboring an aneurysm near a lesion to be treated with FUS. Given the relatively few animal models for larger vascular lesions such as AVM or cavernomas, the presented model offers valuable options to acquire data on the effect of FUS on larger vascular structures.
MR-guided focused ultrasound
common carotid artery
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