Safety and Efficacy of Magnetic Resonance-Guided Focused Ultrasound Surgery With Autofocusing Echo Imaging.
Authors: Chang KW, Rachmilevitch I, Chang WS, Jung HH, Zadicario E, Prus O, Chang JW
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. 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. 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 cm<sup>3</sup> (range: 227-319 cm<sup>3</sup>), while that of the patients with PD was 287.13 cm<sup>3</sup> (range: 271-303 cm<sup>3</sup>). 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 (<i>p</i> > 0.05, autofocusing score showed a <i>p</i>-value of 0.071). 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. clinicaltrials.gov, identifier: NCT03935581.
Introduction
Purpose
Thermal ablation
Study Objective
To evaluate the safety and efficacy of autofocusing echo imaging–guided MRgFUS lesioning, particularly in patients with low skull density ratio (SDR) whose prior focusing methods have failed.
Animal model / Human subject
Homo sapiens (human patients); strain: N/A; age: None; sex: None
Disease model
Essential tremor and Parkinson's disease
MRI or image guidance method
MR-guided focused ultrasound (MRgFUS) using the Exablate 4000 in a 3-T MRI with autofocusing echo imaging (microbubble/US contrast agent DEFINITY) to measure and correct phase/amplitude aberrations; CT was used preprocedurally for skull density ratio and as an initial CT-based correction reference.
Targeted brain region(s)
Thalamus
Outcomes and Safety
Summary of Outcomes
Autofocusing echo imaging MRgFUS produced immediate clinical improvement (reduced dominant-hand CRST in essential tremor and reduced UPDRS Part 3 in Parkinson’s disease) with MRI-confirmed target lesions and no serious adverse events. Successful sonication parameters were the autofocusing echo imaging correction (mean 5.63 autofocusing sonications of ~15 total), Tmax 52–59°C (mean 55.9°C), energy 20–42 kJ (mean 34.8 kJ), with high AF/AF similarity (mean 0.95) and moderate AF/CT similarity (mean ~0.58).
Duration of biological effect
1 month
Safety-related matter
No serious adverse events occurred during or after treatment; no adverse effects of microbubbles were observed and patients reported no headache or nausea. The authors note that prior MRgFUS techniques have been associated with adverse events (e.g., skull marrow necrosis, abnormal thermal or cavitation effects), but none were seen in this small series.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Exablate 4000 / ExAblate Neuro Type 1.0 (InSightec); 1,024-element phased-array transducer; aperture/diameter: None
FUS Frequency
650 kHz
FUS Mode
pulsed
Pulse duration
0.05 ms
Focal Characteristics
Focal depth: None, Focal length: None, Aperture size: None
Treatment frequency
single
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