Factors Related to Successful Energy Transmission of Focused Ultrasound through a Skull : A Study in Human Cadavers and Its Comparison with Clinical Experiences.

OBJECTIVE: Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures. METHODS: For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls. RESULTS: Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05). CONCLUSION: This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required.

Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model.

BACKGROUND: Essential tremor (ET) is one of the most common movement disorders of adults, characterized by postural and kinetic tremor. With drug treatment only partially efficient, new treatments are being developed. OBJECTIVES: The goal of this study was to demonstrate the feasibility of non-thermal focused-ultrasound (FUS) to induce tremor-suppression in an ET rat model. METHODS: Harmaline-induced tremor rats were treated with FUS along the inferior olivary (IO) system. EMG was recorded continuously during treatment in order to quantify FUS-induced tremor suppression. T2-weighted MRI was performed immediately following treatment and periodically thereafter. RESULTS: FUS treatment at an intensity of 27.2 W/cm2 (Isppa) induced significant reduction of tremor in 12 out of 13 ET rats. Tremor frequency was reduced from 6.2 ±â€¯2.8 to 2 ±â€¯1 Hz, p < 0.0003. In 6 of the 12 responding rats, tremor was completely suppressed. Response duration was 70 ±â€¯61s, on average. FUS induced motor response, depicted as movement of the tail and/or the limbs synchronized with the FUS sonication, was also demonstrated both in ET rats and in naïve rats when treated in the medulla oblongata region. CONCLUSIONS: These results demonstrate the feasibly for obtaining significant tremor reduction or tremor suppression induced by non-thermal, non-invasive, reversible focused-ultrasound.

Focused Ultrasound-Induced Suppression of Auditory Evoked Potentials in Vivo.

The goal of this study was to determine the feasibility of focused ultrasound-based neuromodulation affecting auditory evoked potentials (AEPs) in animals. Focused ultrasound-induced suppression of AEPs was performed in 22 rats and 5 pigs: Repetitive sounds were produced, and the induced AEPs were recorded before and repeatedly after FUS treatment of the auditory pathway. All treated animals exhibited a decrease in AEP amplitude post-treatment in contrast to animals undergoing the sham treatment. Suppression was weaker for rats treated at 2.3 W/cm2 (amplitudes decreased to 59.8 ± 3.3% of baseline) than rats treated at 4.6 W/cm2 (36.9 ± 7.5%, p <0.001). Amplitudes of the treated pigs decreased to 27.7 ± 5.9% of baseline. This effect lasted between 30 min and 1 mo in most treated animals. No evidence of heating during treatment or later brain damage/edema was observed. These results demonstrate the feasibility of inducing significant neuromodulation with non-thermal, non-invasive, reversible focused ultrasound. The long recovery times may have clinical implications.