Mathieu Pernot, Jean-Francois Aubry, Mickael Tanter, Anne-Laure Boch, Fabrice Marquet, Michele Kujas, Danielle Seilhean and Mathias Fink
High-intensity focused ultrasonography is known to induce controlled and selective noninvasive destruction of tissues by focusing ultrasonic beams within organs, like a magnifying glass concentrating enough sunlight to burn a hole in paper. Such a technique should be highly interesting for the treatment of deep-seated lesions in the brain. Nevertheless, ultrasonic tissue ablation in the brain has long been hampered by the defocusing effect of the skull bone.
In this in vivo study, the authors used a high-power time-reversal mirror specially designed for noninvasive ultrasonic brain treatment to induce thermal lesions through the skulls of 10 sheep. The sheep were divided into three groups and, depending on group, were killed 1, 2, or 3 weeks after treatment. The thermal lesions were confirmed based on findings of posttreatment magnetic resonance imaging and histological examinations.
After treatment, the basic neurological functions of the animals were unchanged: the animals recovered from anesthesia without any abnormal delay and did not exhibit signs of paralysis or coma. No major behavioral change was observed.
The results provide striking evidence that noninvasive ultrasonographic brain surgery is feasible. Thus the authors offer a novel noninvasive method of performing local brain ablation in animals for behavioral studies. This technique may lead the way to noninvasive and nonionizing treatment of brain tumors and neurological disorders by selectively targeting intracranial lesions. Nevertheless, sheep do not represent a good functional model and extensive work will need to be conducted preferably on monkeys to investigate the effects of this treatment.
W. Jeff Elias, Mohamad Khaled, Justin D. Hilliard, Jean-Francois Aubry, Robert C. Frysinger, Jason P. Sheehan, Max Wintermark and Maria Beatriz Lopes
The purpose of this study was to use MRI and histology to compare stereotactic lesioning modalities in a large brain model of thalamotomy.
A unilateral thalamotomy was performed in piglets utilizing one of 3 stereotactic lesioning modalities: focused ultrasound (FUS), radiofrequency, and radiosurgery. Standard clinical lesioning parameters were used for each treatment; and clinical, MRI, and histological assessments were made at early (< 72 hours), subacute (1 week), and later (1–3 months) time intervals.
Histological and MRI assessment showed similar development for FUS and radiofrequency lesions. T2-weighted MRI revealed 3 concentric lesional zones at 48 hours with resolution of perilesional edema by 1 week. Acute ischemic infarction with macrophage infiltration was most prominent at 72 hours, with subsequent resolution of the inflammatory reaction and coalescence of the necrotic zone. There was no apparent difference in ischemic penumbra or “sharpness” between FUS or radiofrequency lesions. The radiosurgery lesions presented differently, with latent effects, less circumscribed lesions at 3 months, and apparent histological changes seen in white matter beyond the thalamic target. Additionally, thermal and radiation lesioning gradients were compared with modeling by dose to examine the theoretical penumbra.
In swine thalamus, FUS and radiosurgery lesions evolve similarly as determined by MRI, histological examination, and theoretical modeling. Radiosurgery produces lesions with more delayed effects and seemed to result in changes in the white matter beyond the thalamic target.
Dorian Chauvet, Laurent Marsac, Mathieu Pernot, Anne-Laure Boch, Rémy Guillevin, Najat Salameh, Line Souris, Luc Darrasse, Mathias Fink, Mickaël Tanter and Jean-François Aubry
This work aimed at evaluating the accuracy of MR-guided high-intensity focused ultrasound (MRgHIFU) brain therapy in human cadaver heads.
Eighteen heads of fresh human cadavers were removed with a dedicated protocol preventing intracerebral air penetration. The MR images allowed determination of the ultrasonic target: a part of the thalamic nucleus ventralis intermedius implicated in essential tremor. Osseous aberrations were corrected with simulation-based time reversal by using CT data from the heads. The ultrasonic session was performed with a 512-element phased-array transducer system operating at 1 MHz under stereotactic conditions with thermometric real-time MR monitoring performed using a 1.5-T imager.
Dissection, imaging, targeting, and planning have validated the feasibility of this human cadaver model. The average temperature elevation measured by proton resonance frequency shift was 7.9°C ± 3°C. Based on MRI data, the accuracy of MRgHIFU is 0.4 ± 1 mm along the right/left axis, 0.7 ± 1.2 mm along the dorsal/ventral axis, and 0.5 ± 2.4 mm in the rostral/caudal axis.
Despite its limits (temperature, vascularization), the human cadaver model is effective for studying the accuracy of MRgHIFU brain therapy. With the 1-MHz system investigated here, there is millimetric accuracy.
Zhiyuan Xu, Carissa Carlson, John Snell, Matt Eames, Arik Hananel, M. Beatriz Lopes, Prashant Raghavan, Cheng-Chia Lee, Chun-Po Yen, David Schlesinger, Neal F. Kassell, Jean-Francois Aubry and Jason Sheehan
In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology.
Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600–14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140–300 W was used for long-duration sonications and 300–700 W for short-duration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions.
Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages.
This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.