Neuromodulation and ablation with focused ultrasound-toward the future of noninvasive brain therapy

摘要

With an aging patient population and an increased burden of neurological disease,the demand for noninvasive alternatives to open neurosurgical procedures is imperative.Noninvasive or minimally invasive approaches to targeting brain regions include transcranial magnetic stimulation(TMS),transcranial direct current stimulation,temporally interfering electric fields,and focused ultrasound(FUS).Among these modalities,FUS offers a unique combination of target specificity,deep brain penetration,and compatibility with real-time structural and thermal monitoring using magnetic resonance imaging(MRI)and MR thermometry.Depending on the intensity and frequency used,ultrasound can have either modulating or ablative effects on brain tissue.High-intensity MR-guided FUS(MRgFUS)is a noninvasive and effective alternative to conventional deep-brain stimulation and radiofrequency lesioning for essential tremor(ET),and is being investigated for other movement disorders,particularly Parkinson’s disease.Wider clinical implementation of high-intensity ultrasound is challenged by limitations in target selection precision,technical barriers(such as variable penetration and heat deposition)and the possibility of lesion-related adverse effects(Schwartz et al.,2018).Emerging studies,including those from our group(Boutet et al.,2018)are striving to refine targeting of MRgFUS to improve safety and patient clinical outcomes.At the same time,low-intensity FUS(LIFUS)has been found to safely modulate brain activity in rodents,primates,and healthy human subjects(Fomenko et al.,2018).Clinical translation of LIFUS has been hampered however,by a poor understanding of the mechanisms of action,uncertainty over effective sonication parameters and intensities,and conflicting study results due to heterogeneous experimental protocols.In this perspective,the current state of both MRgFUS ablation and LIFUS neuromodulation will be presented.Ongoing technical challenges to delivering ultrasound to the brain,recent innovations in target and parameter selection,and future directions for this emerging nonsurgical alternative are also discussed.