Sustained reduction of essential tremor with low-power non-thermal transcranial focused ultrasound stimulations in humans.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique; when skull aberrations are compensated for, this technique allows, with millimetric accuracy, circumvention of the invasive surgical procedure associated with deep brain stimulation (DBS) and the limited spatial specificity of transcranial magnetic stimulation. OBJECTIVE: /hypothesis: We hypothesize that MR-guided low-power TUS can induce a sustained decrease of tremor power in patients suffering from medically refractive essential tremor. METHODS: The dominant hand only was targeted, and two anatomical sites were sonicated in this exploratory study: the ventral intermediate nucleus of the thalamus (VIM) and the dentato-rubro-thalamic tract (DRT). Patients (N = 9) were equipped with MR-compatible accelerometers attached to their hands to monitor their tremor in real-time during TUS. RESULTS: VIM neurostimulations followed by a low-duty cycle (5 %) DRT stimulation induced a substantial decrease in the tremor power in four patients, with a minimum of 89.9 % reduction when compared with the baseline power a few minutes after the DRT stimulation. The only patient stimulated in the VIM only and with a low duty cycle (5 %) also experienced a sustained reduction of the tremor (up to 93.4 %). Four patients (N = 4) did not respond. The temperature at target was 37.2 ± 1.4 °C compared to 36.8 ± 1.4 °C for a 3 cm away control point. CONCLUSIONS: MR-guided low power TUS can induce a substantial and sustained decrease of tremor power. Follow-up studies need to be conducted to reproduce the effect and better to understand the variability of the response amongst patients. MR thermometry during neurostimulations showed no significant thermal rise, supporting a mechanical effect.

Ultra-short time-echo based ray tracing for transcranial focused ultrasound aberration correction in human calvaria.

OBJECTIVE: Magnetic resonance guided transcranial focused ultrasound holds great promises for treating neurological disorders. This technique relies on skull aberration correction which requires computed tomography (CT) scans of the skull of the patients. Recently, ultra-short time-echo (UTE) magnetic resonance (MR) sequences have unleashed the MRI potential to reveal internal bone structures. In this study, we measure the efficacy of transcranial aberration correction using UTE images. Approach. We compare the efficacy of transcranial aberration correction using UTE scans to CT based correction on four skulls and two targets using a clinical device (Exablate Neuro, Insightec, Israel). We also evaluate the performance of a custom ray tracing algorithm using both UTE and CT estimates of acoustic properties and compare these against the performance of the manufacturer's proprietary aberration correction software. Main results. UTE estimated skull maps in Hounsfield units (HU) had a mean absolute error of 242 ± 20 HU (n=4). The UTE skull maps were sufficiently accurate to improve pressure at the target (no correction: 0.44 ± 0.10, UTE correction: 0.79 ± 0.05, manufacturer CT: 0.80 ± 0.05), pressure confinement ratios (no correction: 0.45 ± 0.10, UTE correction: 0.80 ± 0.05, manufacturer CT: 0.81 ± 0.05), and targeting error (no correction: 1.06 ± 0.42 mm, UTE correction 0.30 ± 0.23 mm, manufacturer CT: 0.32 ± 0.22) (n=8 for all values). When using CT, our ray tracing algorithm performed slightly better than UTE based correction with pressure at the target (UTE: 0.79 ± 0.05, CT: 0.84 ± 0.04), pressure confinement ratios (UTE: 0.80 ± 0.05, CT: 0.84 ± 0.04), and targeting error (UTE: 0.30 ± 0.23 mm, CT: 0.17 ± 0.15). Significance. These 3D transcranial measurements suggest that UTE sequences could replace CT scans in the case of MR guided focused ultrasound with minimal reduction in performance which will avoid ionizing radiation exposure to the patients and reduce procedure time and cost. .

Adaptive Ultrasound Focusing Through the Cranial Bone for Non-invasive Treatment of Brain Disorders.

Focused ultrasound holds great promise in therapy for its ability to target non-invasively deep seated tissues with non-ionizing therapeutic beams. Nevertheless, brain applications have been hampered for decades by the presence of the skull. The skull indeed strongly reflects, refracts and absorbs ultrasound, which defocuses the therapeutic ultrasound beams. In this chapter, we will first show how the structure of the skull impacts the ultrasound beams and how it narrows the frequency range that can be envisioned for transcranial therapy. We will then introduce different methods that have been developed and optimized to compensate the defocusing effect of the bone. Finally, we will provide an overview of past, current and future treatments of brain disorders.

Comparison Between Ray-Tracing and Full-Wave Simulation for Transcranial Ultrasound Focusing on a Clinical System Using the Transfer Matrix Formalism.

Only one high-intensity focused ultrasound device has been clinically approved for transcranial brain surgery at the time of writing. The device operates within 650 and 720 kHz and corrects the phase distortions induced by the skull of each patient using a multielement phased array. Phase correction is estimated adaptively using a proprietary algorithm based on computed-tomography (CT) images of the patient's skull. In this article, we assess the performance of the phase correction computed by the clinical device and compare it to: 1) the correction obtained with a previously validated full-wave simulation algorithm using an open-source pseudo-spectral toolbox and 2) a hydrophone-based correction performed invasively to measure the aberrations induced by the skull at 650 kHz. For the full-wave simulation, three different mappings between CT Hounsfield units and the longitudinal speed of sound inside the skull were tested. All methods are compared with the exact same setup due to transfer matrices acquired with the clinical system for N = 5 skulls and T = 2 different targets for each skull. We show that the clinical ray-tracing software and the full-wave simulation restore, respectively, 84% ± 5% and 86% ± 5% of the pressure obtained with hydrophone-based correction for targets located in central brain regions. On the second target (off-center), we also report that the performance of both algorithms degrades when the average incident angles of the acoustic beam at the skull surface increase. When incident angles are higher than 20°, the restored pressure drops below 75% of the pressure restored with hydrophone-based correction.

Computationally Efficient Transcranial Ultrasonic Focusing: Taking Advantage of the High Correlation Length of the Human Skull.

The phase correction necessary for transcranial ultrasound therapy requires numerical simulation to noninvasively assess the phase shift induced by the skull bone. Ideally, the numerical simulations need to be fast enough for clinical implementation in a brain therapy protocol and to provide accurate estimation of the phase shift to optimize the refocusing through the skull. In this article, we experimentally performed transcranial ultrasound focusing at 900 kHz on N = 5 human skulls. To reduce the computation time, we propose here to perform the numerical simulation at 450 kHz and use the corresponding phase shifts experimentally at 900 kHz. We demonstrate that a 450-kHz simulation restores 94.2% of the pressure when compared with a simulation performed at 900 kHz and 85.0% of the gold standard pressure obtained by an invasive time reversal procedure based on the signal recorded by a hydrophone placed at the target. From a 900- to 450-kHz simulation, the grid size is divided by 8, and the computation time is divided by 10.