Safety and Efficacy of Magnetic Resonance-Guided Focused Ultrasound Surgery With Autofocusing Echo Imaging

Abstract

Objective: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) lesioning is a new treatment for brain disorders. However, the skull is a major barrier of ultrasound sonication in MRgFUS because it has an irregular surface and varies its size and shape among individuals. We recently developed the concept of skull density ratio (SDR) to select candidates for MRgFUS from among patients with essential tremor (ET). However, SDR is not the only factor contributing to successful MRgFUS lesioning treatment-refining the target through exact measurement of the ultrasonic echo in the transducer also improves treatment efficacy. In the present study, we carried out MRgFUS lesioning using an autofocusing echo imaging technique. We aimed to evaluate the safety and efficacy of this new approach, especially in patients with low SDR in whom previous focusing methods have failed.

Methods: From December 2019 to March 2020, we recruited 10 patients with ET or Parkinson's disease (PD) who had a low SDR. Two patients dropped out of the trial due to the screening failure of other medical diseases. In total, eight patients were included: six with ET who underwent MRgFUS thalamotomy and two with PD who underwent MRgFUS pallidotomy. The autofocusing echo imaging technique was used in all cases.

Results: The mean SDR of the patients with ET was 0.34 (range: 0.29-0.39), while that of the patients with PD was 0.41 (range: 0.38-0.44). The mean skull volume of patients with ET was 280.57 cm3 (range: 227-319 cm3), while that of the patients with PD was 287.13 cm3 (range: 271-303 cm3). During MRgFUS, a mean of 15 sonications were performed, among which a mean of 5.63 used the autofocusing technique. The mean maximal temperature (Tmax) achieved was 55.88°C (range: 52-59°C), while the mean energy delivered was 34.75 kJ (range: 20-42 kJ) among all patients. No serious adverse events occurred during or after treatment. Tmax or sonication factors (skull volume, SDR, sonication number, autofocusing score, similarity score, energy range, and power) were not correlated with autofocusing technique (p > 0.05, autofocusing score showed a p-value of 0.071).

Conclusion: Using autofocusing echo imaging lesioning, a safe and efficient MRgFUS treatment, is available even for patients with a low SDR. Therefore, the indications for MRgFUS lesioning could be expanded to include patients with ET who have an SDR < 0.4 and those with PD who have an SDR < 0.45.

Clinical trial registration: clinicaltrials.gov, identifier: NCT03935581.

Keywords: Parkinson’s disease; auto-focusing; echo imaging; essential tremor; magnetic resonance-guided focused ultrasound surgery.

Conflict of interest statement

IR, EZ, and OP was employed by company InSightec. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Chang, Rachmilevitch, Chang, Jung, Zadicario, Prus and Chang.

Figures

FIGURE 1

CONSORT flow diagram of patients for the study.

FIGURE 2

Upper: Ultrasound contrast agent microbubbles emit a spherical wave as a point scattering source. Aberration corrections are deduced directly from the measurement. Lower: Typical recorded signal. Different colors represent different channels. Multiple reflections from the skull dominate the signal. The microbubble signal is invisible at this scale.

FIGURE 3

Ex vivo hydrophone focal scans at the 30 mm off-center point in the skull. The left column shows computed tomography-based correction used as an initial guess. The middle column represents microbubble-based correction, while the right column depicts a hydrophone-based result. The same acoustic power was emitted for all scans. Relative peak intensity values can be used as focusing accuracy criteria. Algorithm similarity score: AF/CT = 0.55, AF/hydrophone = 0.85.

FIGURE 4

Upper: In vivo phase correction compared in a clinical experiment. The left side shows computed tomography (CT)-based correction. The right side represents the echo imaging method. The image is projected onto the transducer surface. Echo imaging correction is calculated independently of the CT-based phases. Algorithm similarity score: AF/CT = 0.63. Lower: Transmission signal amplitudes (relative) measured in vivo using echo imaging. Image is projected onto the transducer surface.

FIGURE 5

Upper: Magnetic resonance (MR) images taken immediately after MR-guided focused ultrasound autofocusing echo imaging thalamotomy in a patient with essential tremor. Lower: MR images taken immediately after MR-guided focused ultrasound autofocusing echo imaging pallidotomy in a patient with Parkinson’s disease.