Magnetic resonance guided focused ultrasound thalamotomy for essential tremor
Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain
The post-treatment effectiveness was evaluated using the clinical rating scale for tremors. Thalamic MRgHIFU had substantial therapeutic effects on patients, based on MRgHIFU-mediated improvements in movement control and significant changes in brain mu rhythms. Ultrasonic thalamotomy may reduce hyper-excitable activity in the motor cortex, resulting in normalized behavioral activity after sonication treatment. Thus, non-invasive and spatially accurate MRgHIFU technology can serve as a potent therapeutic tool with broad clinical applications 1).
Magnetic resonance guided focused ultrasound (MRgFUS) for thalamotomy is a safe, effective and less-invasive surgical method for treating medication-refractory essential tremor (ET). However, several issues must be resolved before clinical application of MRgFUS, including optimal patient selection and management of patients during treatment 2).
Jung et al. found different MRI pattern evolution after MRgFUS for white matter and gray matter. Their results suggest that skull characteristics, such as low skull density, should be evaluated prior to MRgFUS to successfully achieve thermal rise 3).
With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a Health Insurance Portability and Accountability Act (HIPAA)-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. Diffusion tensor imaging (DTI) (DT MR imaging) studies at 3 Tesla were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation.
Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the semioval center, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P < .001).
DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor 4).
If larger trials validate the safety and ascertain the efficacy and durability of this new approach, it might change the way that patients with essential tremor and potentially other disorders are treated 5).
In a pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized controlled trials will be required to assess the procedure’s efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.) 6).
MR examinations were performed before and 2 days after the ultrasound functional neurosurgical treatment to visualize the targets on T2-weighted images and determine their coordinates. Thirty consecutive targets were reconstructed: 18 were in the central lateral nucleus of the medial thalamus (central lateral thalamotomies against neurogenic pain), 1 in the centrum medianum thalamic nucleus (centrum medianum thalamotomy against essential tremor), 10 on the pallido-thalamic tract (pallido-thalamic tractotomies against Parkinson’s disease), and 1 on the cerebello-thalamic tract (cerebello-thalamic tractotomy against essential tremor). We describe a method for reconstruction of the lesion coordinates on post-treatment MR images, which were compared with the desired atlas target coordinates. We also calculated the accuracy of the intra-operative target placement, thus allowing to determine the global, planning, and device accuracies. We also estimated the target lesion volume.
Moser et al. found mean absolute global targeting accuracies of 0.44 mm for the medio-lateral dimension (standard deviation 0.35 mm), 0.38 mm for the antero-posterior dimension (standard deviation 0.33 mm), and 0.66 mm for the dorso-ventral dimension (standard deviation 0.37 mm). Out of the 90 measured coordinates, 83 (92.2%) were inside the millimeter domain. The mean three-dimensional (3D) global accuracy was 0.99 mm (standard deviation 0.39 mm). The mean target volumes, reconstructed from surface measurements on 3D T1 series, were 68.5 mm(3) (standard deviation 39.7 mm(3)), and 68.9 mm(3) (standard deviation 40 mm(3)) using an ellipsoidal approximation 7).