Consensus for clinical applications of transcranial magnetic resonance-guided focused ultrasound

Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) is an advanced neuromodulation technique that leverages the power of magnetic resonance imaging (MRI) for guidance and temperature monitoring and focused ultrasound waves to perform noninvasive brain modulation.[1] This revolutionary method opens new avenues for treating various brain disorders, including essential tremor (ET), Parkinson’s disease (PD), and some psychiatric conditions, without requiring open surgery.[2–4] However, there is a lack of consensus on standardized protocols, particularly those tailored to Asian demographics. To promote the standardized application of MRgFUS and to facilitate informed decision-making in clinical practice, specialists in the field collaborated to establish a comprehensive consensus following extensive discussions. The consensus centers on the ExAblate Neuro devices (InSightec, Tirat Carmel, Israel) because these devices are currently the only Food and Drug Administration (FDA)-approved focused ultrasound (FUS) system for brain thermoablation, and the majority of accumulated clinical expertise in the field largely stems from their utilization. This consensus comprehensively elucidates indications, contraindications, procedures, and clinical management. The recommendations in Table 1 aim to enhance MRgFUS-centered patient care and clinical protocols. The full-length version of the consensus is shown in the Supplementary Materials, https://links.lww.com/CM9/C153. Table 1 - Summary of the recommendation for the application of MRgFUS. Items Recommendation Indications Current indications ETPD potential indications NPOCDMDDEpilepsyDystonia Contraindications Absolute MRI contraindicationAbnormal bleeding and/or coagulopathyPoorly controlled medical conditionsLack of cooperation Relative Currently pregnant or lactatingLow skull density ratioAnatomical variations affecting target accessibility Preprocedural System preparation DQA Patient preparation Planning scans and target selectionHair shaveHead frame placementIntravenous access Intraprocedural Alignment of the ultrasound focus Low-energy sonications (Temperature: between 40°C and 45°C)Target correction Confirmation of the target Increase energy (Temperature: between 46°C and 52°C)Physical exam Therapeutic ablation High-energy sonications (Temperature: between 54°C and 60°C)Physical exam and target correctionIntraprocedural scans Postprocedural Post procedure MRI (within 24 hours)Post procedure physical exam Complications Surgical complications Head frame and procedure-related complicationsMRI environment effects Target-related Complications Neurological deficits associated with the adjacent areas DQA: Daily quality assurance; ET: Essential tremor; MDD: Major depressive disorder; MRgFUS: Magnetic resonance-guided focused ultrasound; MRI: Magnetic resonance imaging; NP: Neuropathic pain; OCD: Obsessive-compulsive disorder; PD: Parkinson’s disease. Recommendations Indications for MRgFUS (1) Medication-refractory tremors (ET and tremor-dominant PD) can be addressed by unilateral MRgFUS thalamotomy. This technique involves MRgFUS-mediated thermoablation of the ventral intermediate nucleus of the thalamus and has been validated as a safe and efficacious approach for managing ET.[5] It is a viable alternative, particularly for patients who are not candidates for deep brain stimulation (DBS) due to contraindications or unfavorable risk-to-benefit profiles. MRgFUS thalamotomy is also deemed suitable for tremor-dominant PD cases.[6] Nonetheless, tremors should be acknowledged as merely one facet of the complex spectrum of PD symptoms. The progressive course of the disease and its implications must be meticulously evaluated when determining patient eligibility. The treatment of ET and tremor-dominant PD using MRgFUS thalamotomy has been approved by the FDA and the National Medical Products Administration (NMPA). (2) Medication-refractory PD: Unilateral subthalamotomy and pallidotomy have shown encouraging prospects for improving motor functionality in patients with PD, as inferred from the preliminary results of randomized controlled trials.[7,8] Notably, unilateral pallidotomy has been proven effective in reducing dyskinesia, a common complication associated with PD treatment. The FDA has officially approved the unilateral pallidotomy procedure for managing medication-refractory moderate-to-severe motor symptoms in patients with PD, recognizing its therapeutic value. Additionally, the exploration of MRgFUS-guided pallidothalamic tractotomy not only holds promise for alleviating motor impairments but also suggests potential benefits for non-motor symptoms. (3) Neuropathic pain (NP): Bilateral MRgFUS central lateral thalamotomy, which targets the central lateral nucleus of the thalamus (CLT), exhibits early signs of therapeutic potential for managing NP. This optimism is grounded in the findings of initial pilot observational studies. Despite the encouraging preliminary outcomes, it is essential to underscore that the existing body of evidence remains at a nascent stage and lacks robustness. Therefore, although this procedure suggests a novel avenue for NP relief, it has not yet been endorsed for routine clinical deployment. (4) Bilateral MRgFUS anterior capsulotomy, targeting the anterior limb of the internal capsule (ALIC), has emerged as a potential intervention for obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Preliminary findings suggest that this innovative, noninvasive approach may offer symptomatic relief by modulating the neural circuits implicated in these psychiatric conditions. While the evidence is still evolving and is primarily based on case reports and small studies, the safety and efficacy of the technique are encouraging, stimulating interest among experts in the field. (5) Epilepsy: While MRgFUS presents as a potential novel therapy for epilepsy, clinical adoption is premature without sufficient evidence. Further research is required in this area. (6) Dystonia: Pilot research suggests that MRgFUS thalamotomy targeting the ventrooral nucleus may have the potential to treat focal hand dystonia. However, clinical implementation is not advisable without robust evidence. (7) Blood-brain barrier opening (BBBO): MRgFUS, when employed at low intensity, facilitates a BBBO, overcoming the inherent restriction posed by the intact BBB. MRgFUS-induced BBBO is a highly promising strategy for treating a wide array of neurological conditions such as Alzheimer’s disease, PD, and brain tumors. However, to fully harness this potential, large-scale studies are imperative to establish standardized and safe treatment protocols and further elucidate their therapeutic effect. MRgFUS can induce small thermal lesions in the thalamic and subthalamic regions. While larger or deeper seated targets, as well as those situated in more peripheral locations, are theoretically accessible via this modality, they may entail protracted treatment sessions or necessitate modified patient positioning to counteract the increased anatomical challenges and ensure therapeutic efficacy. Consequently, the patient populations primarily suitable for MRgFUS interventions are those diagnosed with conditions that are traditionally managed invasively, specifically those for which DBS constitutes the standard therapeutic intervention. This approach resonates with the advancing paradigm shift favoring noninvasive alternatives such as MRgFUS for conditions historically addressed by DBS, highlighting its potential as a refined and minimally invasive strategy in the modern neurosurgical repertoire. Contraindications Absolute contraindication: (1) MRI contraindications. (2) Abnormal bleeding and/or coagulopathy. (3) Poorly controlled medical conditions, including severe neuropsychiatric disorders, cognitive impairment, serious neurological diseases, severe systemic diseases, and surgical contraindications. (4) Lack of cooperation. (5) Currently pregnant or lactating. Relative contraindication: (1) Head lesions affecting target accessibility and ultrasound transmission. (2) Low skull density ratio. Preoperative assessment (1) A comprehensive evaluation of MRgFUS treatment, including indications, contraindications, medications, and cost-effectiveness. (2) Coagulopathies should be corrected to achieve an international normalized ratio of less than 1.2 and a platelet count of more than 100,000/μL. Process of MRgFUS MRgFUS system preparation: Daily quality assurance (DQA) of the MRgFUS system procedure should be conducted the day before surgery to ensure that the system works well. Patient preparation: (1) Preoperative head magnetic resonance (MR) and computerized tomography (CT) images should be obtained to localize the target and mark the “no-pass zones”. (2) Meticulous hair shaving is important to avoid air bubbles trapped in the hair. (3) The stereotactic frame can be placed under local anesthesia only, with a position as inferior as possible on the head to optimize the utilization of active transducer elements. Intraprocedural: (1) Three procedural planes of anatomical T2 sequences can be acquired for co-registration of the procedural imaging with pre-procedure MRI, CT, and target localization. (2) Low-energy sonication is initiated to calibrate the ultrasound focus and target. Initial heating between 40°C and 45°C is ideal to align the ultrasound focus, as these temperatures are unlikely to damage tissue or cause neurological effects. The accuracy of the thermal rise should be assessed only in the phase orthogonal to the encoding direction due to a known thermal shift in the frequency-encoding direction of MR thermography. The accuracy should be confirmed in all three directions. (3) Sonications producing temperatures between 46°C and 52°C that can then be performed to confirm the target by eliciting reversible neurological and/or sensory changes and tremor improvement. (4) High-energy sonication can then be performed to achieve higher temperatures (between 54°C and 60°C) to ablate the target until tremor suppression occurs. (5) An intraprocedural T2 sequence is performed after a group of sonications between 56°C and 60°C. If the patient experiences significant clinical improvement and intraprocedural T2-weighted imaging demonstrates a hyperintense lesion with a diameter exceeding 4–5 mm immediately after treatment, the procedure may be completed. Postprocedural: A brain MRI should be repeated within 24 h after the operation to evaluate the ablation area, check for cerebral hemorrhage, and assess for cerebral edema. Complications (1) A key concern is the potential for injury to nontargeted brain tissues. Despite the high precision of this technique, there remains a risk of unintended heating and damage to adjacent areas, which could lead to neurological deficits such as numbness, weakness, or speech difficulties. These adverse effects are closely monitored and mitigated through real-time thermometry and careful dosing with ultrasound energy; however, this possibility cannot be entirely eliminated. (2) Another complication involves adverse reactions to the procedure itself, such as headaches, scalp discomfort from the fixation device, and nausea due to the extended period spent in the MRI environment. These symptoms are usually transient and manageable with supportive care. Additionally, given the use of anesthesia or sedation in some cases, there is a small risk associated with these medications, including allergic reactions or respiratory depression. MRgFUS is recognized for its minimally invasive approach; however, similar to other medical procedures, it is not devoid of potential complications. While the risk profile is generally favorable compared with conventional surgery, complications can arise and should be carefully considered. Funding This work was supported by the grants from the National Natural Science Foundation of China (Nos. 82151309 and 82302146). Conflicts of interest None.