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OBJECTIVE: Tractography-based targeting of the thalamic ventral intermediate nucleus (T-VIM) is a novel method conferring patient-specific selection of VIM coordinates for tremor surgery; however, its accuracy and clinical utility in magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy compared to conventional indirect targeting has not been specifically addressed. This retrospective study sought to compare the treatment locations and potential adverse effect profiles of T-VIM with indirect targeting in a large cohort of MRgFUS thalamotomy patients. METHODS: T-VIM was performed using diffusion tractography outlining the pyramidal and medial lemniscus tracts in 43 MRgFUS thalamotomy patients. T-VIM coordinates were compared with the indirect treatment coordinates used in the procedure. Thalamotomy lesions were delineated on postoperative T1-weighted images and displaced ("translated") by the anteroposterior and mediolateral difference between T-VIM and treatment coordinates. Both translated and actual lesions were normalized to standard space and subsequently overlaid with areas previously reported to be associated with an increased risk of motor and sensory adverse effects when lesioned during MRgFUS thalamotomy. RESULTS: T-VIM coordinates were 2.18 mm anterior and 1.82 mm medial to the "final" indirect treatment coordinates. Translated lesions lay more squarely within the boundaries of the VIM compared to nontranslated lesions and showed significantly less overlap with areas associated with sensory adverse effects. Translated lesions overlapped less with areas associated with motor adverse effects; however, this difference was not significant. CONCLUSIONS: T-VIM leads to the selection of more anterior and medial coordinates than the conventional indirect methods. Lesions moved toward these anteromedial coordinates avoid areas associated with an increased risk of motor and sensory adverse effects, suggesting that T-VIM may improve clinical outcomes.

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OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in patients with Parkinson's disease (PD). However, the underlying mechanism of tremor suppression is not well understood. Stimulation of white matter tracts, such as the dentatorubrothalamic tract (DRT), might be involved. Also, side effects, including dysarthria, might result from (unwanted) stimulation of white matter tracts in proximity to the STN. The aim of this study was to establish an association between stimulation effect on tremor and dysarthria and stimulation location relative to relevant white matter tracts. METHODS: In 35 PD patients in whom a bilateral STN DBS system was implanted, the authors established clinical outcome measures per electrode contact. The distance from each stimulation location to the center of the DRT, corticopontocerebellar tract, pyramidal tract (PT), and medial lemniscus was determined using diffusion-weighted MRI data. Clinical outcome measures were subsequently related to the distances to the white matter tracts. RESULTS: Patients with activated contacts closer to the DRT showed increased tremor improvement. Proximity of activated contacts to the PT was associated with dysarthria. CONCLUSIONS: Proximity to specific white matter tracts is associated with tremor outcome and side effects in DBS. This knowledge can help to optimize both electrode placement and postsurgical electrode contact selection. Presurgical white matter tract visualization may improve targeting and DBS outcome. These findings are of interest not only for treatment in PD, but potentially also for other (movement) disorders.

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OBJECTIVE The dentatorubrothalamic tract (DRTT) has been suggested as the anatomical substrate for deep brain stimulation (DBS)-induced tremor alleviation. So far, little is known about how accurately and reliably tracking results correspond to the anatomical DRTT. The objective of this study was to systematically investigate and validate the results of different tractography approaches for surgical planning. METHODS The authors retrospectively analyzed 4 methodological approaches for diffusion tensor imaging (DTI)-based fiber tracking using different regions of interest in 6 patients with essential tremor. Tracking results were analyzed and validated with reference to MRI-based anatomical landmarks, were projected onto the stereotactic atlas of Morel at 3 predetermined levels (vertical levels -3.6, -1.8, and 0 mm below the anterior commissure-posterior commissure line), and were correlated to clinical outcome. RESULTS The 4 different methodologies for tracking the DRTT led to divergent results with respect to the MRI-based anatomical landmarks and when projected onto the stereotactic atlas of Morel. There was a statistically significant difference in the lateral and anteroposterior coordinates at the 3 vertical levels (p < 0.001, 2-way ANOVA). Different fractional anisotropy values ranging from 0.1 to 0.46 were required for anatomically plausible tracking results and led to varying degrees of success. Tracking results were not correlated to postoperative tremor reduction. CONCLUSIONS Different tracking methods can yield results with good anatomical approximation. The authors recommend using 3 regions of interest including the dentate nucleus of the cerebellum, the posterior subthalamic area, and the precentral gyrus to visualize the DRTT. Tracking results must be cautiously evaluated for anatomical plausibility and accuracy in each patient.

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OBJECTIVE: Surgical management of brainstem lesions is challenging due to the highly compact, eloquent anatomy of the brainstem. This study aimed to evaluate the safety and efficacy of preoperative diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in brainstem cavernous malformations (CMs). METHODS: A prospective randomized controlled clinical trial was performed by using stratified blocked randomization. The primary eligibility criterion of the study was being a surgical candidate for brainstem CMs (with informed consent). The study enrolled 23 patients who underwent preoperative DTI/DTT and 24 patients who did not (the control group). The pre- and postoperative muscle strength of both limbs and modified Rankin Scale (mRS) scores were evaluated. Muscle strength of any limb at 12 months after surgery at the clinic visit was the primary outcome; worsened muscle strength was considered to be a poor outcome. Outcome assessors were blinded to patient management. This study reports the preliminary results of the interim analysis. RESULTS: The cohort included 47 patients (22 women) with a mean age of 35.7 years. The clinical baselines between these 2 groups were not significantly different. In the DTI/DTT group, the corticospinal tract was affected in 17 patients (73.9%): it was displaced, deformed/partially interrupted, or completely interrupted in 6, 7, and 4 patients, respectively. The surgical approach and brainstem entry point were adjusted in 3 patients (13.0%) based on DTI/DTT data. The surgical morbidity of the DTI/DTT group (7/23, 30.4%) was significantly lower than that of the control group (19/24, 79.2%, p = 0.001). At 12 months, the mean mRS score (1.1, p = 0.034) and percentage of patients with worsened motor deficits (4.3%, p = 0.006) were significantly lower in the DTI/DTT group than in the control group (1.7% and 37.5%). Multivariate logistic regression identified the absence of preoperative DTI/DTT (OR 0.06, 95% CI 0.01-0.73, p = 0.028) and use of the 2-point method (OR 4.15, 95% CI 1.38-12.49, p = 0.011) as independent adverse factors for a worsened motor deficit. The multivariate model found a significant correlation between poor mRS score and both an increased preoperative mRS score (t = 3.559, p = 0.001) and absence of preoperative DTI/DTT (t = -2.747, p = 0.009). CONCLUSIONS: DTI/DTT noninvasively allowed for visualization of the anatomical relationship between vital tracts and pathologies as well as facilitated the brainstem surgical approach and entry-point decision making. The technique was valuable for complex neurosurgical planning to reduce morbidity. Nonetheless, DTI/DTT data should be interpreted cautiously.■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized controlled trial; evidence: class I. Clinical trial registration no.: NCT01758211 (ClinicalTrials.gov).

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OBJECTIVE The objective of this study was to evaluate the utility of diffusion tensor imaging (DTI) tractography-based targeting of the dentatorubrothalamic tract (DRT) for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in patients with essential tremor (ET) and correlate postprocedural tract disruption with clinical outcomes. METHODS Four patients received preprocedural and immediate postprocedural DTI in addition to traditional anatomical MRI sequences for MRgFUS thalamotomy. Optimal ablation sites were selected based on the patient-specific location of the DRT as demonstrated by DTI (direct targeting) and correlated with traditional atlas-based measurements for thalamic ventral intermediate nucleus (Vim) lesioning (indirect targeting). Fiber tracts were displayed three-dimensionally during the procedure and used in conjunction with clinical signs of tremor control for fine correction of the ablation site. Immediately following the conclusion of the procedure, the MRgFUS head frame was removed and patients were placed in a 32-channel MRI head coil for follow-up DTI and anatomical MRI sequences. RESULTS All patients had excellent postoperative tremor control and successful pre- and postprocedural DTI fiber tracking of the corticospinal tract, medial lemniscus, and DRT. Immediate postprocedure DTI failed to track the DRT ipsilateral to the lesion site with a preserved contralateral DRT, coincident with substantial resolution of contralateral tremor. CONCLUSIONS DTI can reliably identify the optimal ablation target and demonstrates tract disruption on immediate postprocedural imaging. A clinical improvement of ET was observed immediately following the procedure, correlating with DRT disruption and suggesting that interruption of the DRT is a consequence of clinically successful MRgFUS thalamotomy. These findings may have utility for both MRgFUS procedure planning in surgically naive patients and retreatment of patients who have previously undergone unsuccessful thalamic Vim lesioning.

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OBJECTIVE The ventral intermediate nucleus (VIM) of the thalamus is not visible on structural MRI. Therefore, direct VIM targeting methods for stereotactic tremor surgery are desirable. The authors previously described a direct targeting method for visualizing the VIM and its structural connectivity using deterministic tractography. In this combined electrophysiology and imaging study, the authors investigated the electrophysiology within this tractography-defined VIM (T-VIM). METHODS Thalamic neurons were classified based on their relative location to the T-VIM: dorsal, within, and ventral to the T-VIM. The authors identified the movement-responsive cells (kinesthetic and tremor cells), performed spike analysis (firing rate and burst index), and local field potential analysis (area under the curve for 13-30 Hz). Tremor efficacy in response to microstimulation along the electrode trajectory was also assessed in relation to the T-VIM. RESULTS Seventy-three cells from a total of 9 microelectrode tracks were included for this analysis. Movement-responsive cells (20 kinesthetic cells and 26 tremor cells) were identified throughout the electrode trajectories. The mean firing rate and burst index of cells (n = 27) within the T-VIM are 18.8 ± 9.8 Hz and 4.5 ± 5.4, respectively. Significant local field potential beta power was identified within the T-VIM (area under the curve for 13-30 Hz = 6.6 ± 7.7) with a trend toward higher beta power in the dorsal T-VIM. The most significant reduction in tremor was also observed in the dorsal T-VIM. CONCLUSIONS The electrophysiological findings within the VIM thalamus defined by tractography, or T-VIM, correspond with the known microelectrode recording characteristics of the VIM in patients with tremor.

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OBJECT: Resection of brainstem cavernous malformations (BSCMs) may reduce the risk of stepwise neurological deterioration secondary to hemorrhage, but the morbidity of surgery remains high. Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are neuroimaging techniques that may assist in the complex surgical planning necessary for these lesions. The authors evaluate the utility of preoperative DTI and DTT in the surgical management of BSCMs and their correlation with functional outcome. METHODS: A retrospective review was conducted to identify patients who underwent resection of a BSCM between 2007 and 2012. All patients had preoperative DTI/DTT studies and a minimum of 6 months of clinical and radiographic follow-up. Five major fiber tracts were evaluated preoperatively using the DTI/DTT protocol: 1) corticospinal tract, 2) medial lemniscus and medial longitudinal fasciculus, 3) inferior cerebellar peduncle, 4) middle cerebellar peduncle, and 5) superior cerebellar peduncle. Scores were applied according to the degree of distortion seen, and the sum of scores was used for analysis. Functional outcomes were measured at hospital admission, discharge, and last clinic visit using modified Rankin Scale (mRS) scores. RESULTS: Eleven patients who underwent resection of a BSCM and preoperative DTI were identified. The mean age at presentation was 49 years, with a male-to-female ratio of 1.75:1. Cranial nerve deficit was the most common presenting symptom (81.8%), followed by cerebellar signs or gait/balance difficulties (54.5%) and hemibody anesthesia (27.2%). The majority of the lesions were located within the pons (54.5%). The mean diameter and estimated volume of lesions were 1.21 cm and 1.93 cm(3), respectively. Using DTI and DTT, 9 patients (82%) were found to have involvement of 2 or more major fiber tracts; the corticospinal tract and medial lemniscus/medial longitudinal fasciculus were the most commonly affected. In 2 patients with BSCMs without pial presentation, DTI/DTT findings were important in the selection of the surgical approach. In 2 other patients, the results from preoperative DTI/DTT were important for selection of brainstem entry zones. All 11 patients underwent gross-total resection of their BSCMs. After a mean postoperative follow-up duration of 32.04 months, all 11 patients had excellent or good outcome (mRS Score 0-3) at the time of last outpatient clinic evaluation. DTI score did not correlate with long-term outcome. CONCLUSIONS: Preoperative DTI and DTT should be considered in the resection of symptomatic BSCMs. These imaging studies may influence the selection of surgical approach or brainstem entry zones, especially in deep-seated lesions without pial or ependymal presentation. DTI/DTT findings may allow for more aggressive management of lesions previously considered surgically inaccessible. Preoperative DTI/DTT changes do not appear to correlate with functional postoperative outcome in long-term follow-up.

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