Tractography-based targeting of the ventral intermediate nucleus: accuracy and clinical utility in MRgFUS thalamotomy

Manish Ranjan University Health Network, Toronto;
Krembil Brain Institute, Toronto;

Search for other papers by Manish Ranjan in
Current site
Google Scholar
PubMed
Close
 MBBS, MCh
,
Gavin J. B. Elias University Health Network, Toronto;
Krembil Brain Institute, Toronto;

Search for other papers by Gavin J. B. Elias in
Current site
Google Scholar
PubMed
Close
 BA
,
Alexandre Boutet University Health Network, Toronto;
Joint Department of Medical Imaging, University of Toronto, Ontario;

Search for other papers by Alexandre Boutet in
Current site
Google Scholar
PubMed
Close
 MD, MSc
,
Jidan Zhong Krembil Brain Institute, Toronto;

Search for other papers by Jidan Zhong in
Current site
Google Scholar
PubMed
Close
 PhD
,
Powell Chu Krembil Brain Institute, Toronto;

Search for other papers by Powell Chu in
Current site
Google Scholar
PubMed
Close
 MSc
,
Jurgen Germann University Health Network, Toronto;

Search for other papers by Jurgen Germann in
Current site
Google Scholar
PubMed
Close
 PhD
,
Gabriel A. Devenyi Cerebral Imaging Center, Douglas Mental Health University, McGill University; Departments of
Psychiatry and

Search for other papers by Gabriel A. Devenyi in
Current site
Google Scholar
PubMed
Close
 PhD
,
M. Mallar Chakravarty Cerebral Imaging Center, Douglas Mental Health University, McGill University; Departments of
Psychiatry and
Biological and Biomedical Engineering, McGill University, Montreal, Quebec;

Search for other papers by M. Mallar Chakravarty in
Current site
Google Scholar
PubMed
Close
 PhD
,
Alfonso Fasano University Health Network, Toronto;
Krembil Brain Institute, Toronto;
The Edmond J. Safra Program in Parkinson’s Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto;

Search for other papers by Alfonso Fasano in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Kullervo Hynynen Sunnybrook Research Institute, Sunnybrook Health Sciences Center, University of Toronto;
Department of Medical Biophysics, University of Toronto;
Institute of Biomaterials and Biomedical Engineering, University of Toronto;

Search for other papers by Kullervo Hynynen in
Current site
Google Scholar
PubMed
Close
 PhD
,
Nir Lipsman Division of Neurosurgery, Sunnybrook Health Sciences Center, University of Toronto; and
Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Center, University of Toronto, Ontario, Canada

Search for other papers by Nir Lipsman in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Clement Hamani Division of Neurosurgery, Sunnybrook Health Sciences Center, University of Toronto; and
Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Center, University of Toronto, Ontario, Canada

Search for other papers by Clement Hamani in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Walter Kucharczyk University Health Network, Toronto;
Joint Department of Medical Imaging, University of Toronto, Ontario;

Search for other papers by Walter Kucharczyk in
Current site
Google Scholar
PubMed
Close
 MD
,
Michael L. Schwartz Division of Neurosurgery, Sunnybrook Health Sciences Center, University of Toronto; and

Search for other papers by Michael L. Schwartz in
Current site
Google Scholar
PubMed
Close
 MD, MSc
,
Andres M. Lozano University Health Network, Toronto;
Krembil Brain Institute, Toronto;

Search for other papers by Andres M. Lozano in
Current site
Google Scholar
PubMed
Close
 MD, PhD
, and
Mojgan Hodaie University Health Network, Toronto;
Krembil Brain Institute, Toronto;

Search for other papers by Mojgan Hodaie in
Current site
Google Scholar
PubMed
Close
 MD, MSc
Full access

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.

ABBREVIATIONS

AC-PC = anterior commissure–posterior commissure; AP = anteroposterior; DBS = deep brain stimulation; DWI = diffusion-weighted imaging; MER = microelectrode recording; M-L = mediolateral; ML = medial lemniscus; MRgFUS = magnetic resonance imaging–guided focused ultrasound; PT = pyramidal tract; ROI = region of interest; SHSC = Sunnybrook Health Science Centre; VIM = ventral intermediate nucleus; T-VIM = tractography-based targeting of the VIM; TWH = Toronto Western Hospital; Voa = ventro-oralis anterior nucleus; Vop = ventro-oralis posterior nucleus.

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.

In Brief

The authors studied a novel tractography method to target the ventral intermediate nucleus (T-VIM) for MRI-guided focused ultrasound (MRgFUS) thalamotomy and compared it with the conventional targeting method to assess its clinical utility and accuracy. The T-VIM coordinates were statistically different from coordinates obtained with the conventional indirect method. The spatial location of the MRgFUS thalamotomy lesion moves away favorably from the adverse effect zone, with T-VIM predicting a favorable clinical profile.

Magnetic resonance imaging–guided focused ultrasound (MRgFUS) is a novel, minimally invasive, and recently FDA-approved transcranial procedure for the treatment of essential tremor.4,5,16 As with other surgical treatments such as deep brain stimulation (DBS) and radiofrequency thalamotomy, MRgFUS for tremor typically targets the ventral intermediate nucleus (VIM) of the thalamus, a structure that comprises a key hub in the brain’s cerebello-thalamo-cortical network.7 However, it is difficult to target the VIM directly because of its indiscernibility on routinely acquired MRI sequences and subtle interindividual variation with respect to its location within the thalamus.1 Historically, the VIM has been targeted indirectly using atlas-derived measurements that reference common stereotactic landmarks such as the anterior and posterior commissures, with invasive microelectrode recording (MER) employed to refine the final target intraoperatively. While indirect approaches are still used with great frequency, they offer only generalized estimates of the VIM’s location and thus often fail to account for interindividual anatomical variation and may contribute to imprecise target selection and suboptimal clinical outcomes.1,8,11,21 This is problematic since there is consensus that precise and accurate targeting is crucial for achieving good therapeutic outcomes and avoiding adverse effects.17,18 And this is particularly important for MRgFUS because of its noninvasive approach, absence of MER, and irreversible ablative nature.

We have previously described a tractography-based targeting method that delineates the VIM (T-VIM) according to its position relative to neighboring tracts of interest—specifically, the pyramidal tract (PT) and medial lemniscus (ML).12,19 While prior studies have provided preliminary accounts of T-VIM for DBS and radiofrequency procedures,12,19 the technique’s clinical relevance and validity in MRgFUS thalamotomy as compared to conventional targeting methods have not been thoroughly investigated. We have recently shown, through topographic analysis of thalamotomy lesions, that the most common postprocedural adverse effects (i.e., motor and sensory complications) in MRgFUS are associated with specific brain regions that partially encircle the typical VIM target.2 The areas at increased risk of motor and sensory adverse effects were found to roughly overlap with the PT and ML tracts, respectively. Given this putative relationship between tracts and adverse effects, one important potential benefit of T-VIM for MRgFUS may be to lower the incidence of adverse effects, which previous clinical trials have found to be fairly high.5

Using retrospective data from a large patient cohort with medically refractory tremors treated with MRgFUS thalamotomy, we sought to compare T-VIM coordinates with indirect targeting coordinates and to explore the probable clinical utility of the tractography-based targeting method through the lens of lesion overlap with previously identified adverse effect zones.2 Specifically, we sought to understand whether target adjustment during MRgFUS away from the indirect target and instead toward the T-VIM target might be associated with a more favorable adverse effect profile.

Methods

Patient Selection and Treatment

After obtaining institutional research ethics board approval (principal investigators: A.M.L. and M.L.S.), we retrospectively studied 43 patients with essential tremor or tremor-dominant Parkinson’s disease who had undergone MRgFUS thalamotomy at the Sunnybrook Health Science Centre (SHSC) or Toronto Western Hospital (TWH) between 2012 and 2017. All treated patients had been assessed by a multidisciplinary team and had been judged to be excellent candidates for VIM MRgFUS thalamotomy. Patients with inadequate diffusion-weighted imaging (DWI), a clinical follow-up less than 3 months, or sham procedures (as part of a clinical trial) were excluded.

The MRgFUS thalamotomy procedure was performed as described previously,16 with treatment coordinates for each case first derived from indirect stereotactic algorithms. Briefly, VIM thalamotomy coordinates were selected in the anterior commissure–posterior commissure (AC-PC) plane 15 mm from the midline or 11 mm from the lateral wall of the third ventricle and one-fourth of the AC-PC length anterior to the PC (approximately 7 mm anterior to the PC). This planned target was initially sonicated at a lower acoustic power with a test sonication; subsequent sonications with an incrementally increasing temperature or duration were then delivered in order to produce the desired ablative lesion. The initial target was refined as necessary based on intraprocedural clinical feedback and observations relating to adverse effects or lack of tremor improvement. In the event that the target was refined, a smaller tentative lesion at the new location was created, and this lesion was progressively enlarged depending on the individual clinical response.16 Both the “planned” (i.e., conventional atlas-derived stereotactic coordinates) and the “final” (i.e., coordinates after any intraprocedural adjustments) indirect targeting coordinates for each MRgFUS procedure were recorded from the sonication machine (Exablate Neuro, Insightec). Patient charts were retrospectively reviewed, and acute motor and sensory adverse effects were tracked.

DWI Preprocessing and Tractography

The processing pipeline utilized to generate tracts of interest (PT and ML tracts) has been described elsewhere.19 Briefly, DWI sequences (SHSC: GE Healthcare Discovery MR650 3-T MRI system, 1 b = 0 image, 60 directions at b = 1000 s/mm2, TR 9000 msec, TE 83 msec, voxel size: isotropic 2 mm; TWH: GE Healthcare HDx 3-T scanner, 3 b = 0 images, 30 directions at b = 1000 s/mm2, TR 11700 msec, TE 108 msec, voxel size: isotropic 2 mm) were eddy-current and movement-artifact corrected in FSL (FMRIB Software Library) with corresponding rotational correction of b-vectors.15 The mean DW image was generated based on averaging the DW images. PT and ML fiber tracking was conducted in MRtrix3 (http://www.brain.org.au/software/) using a deterministic (or probabilistic in cases in which the PT or ML could not be traced deterministically) tractography algorithm. For the PT, a seed region of interest (ROI) was placed in the cerebral peduncle and an inclusion ROI was placed in the ipsilateral precentral gyrus. For the ML, the seed ROI was located in the dorsal column of the brainstem and the inclusion ROI was placed in the ipsilateral postcentral gyrus. The algorithm generated up to 1000 tracts with a minimum length of 10 mm and maximum length of 200 mm. Tracking parameters included a step size of 1 mm, minimum radius of curvature of 1 mm, fractional anisotropy (FA) cutoff of 0.2, and tracking angles at 45°.

T-VIM

Preoperative T1-weighted images (SHSC: GE Healthcare Discovery MR650 3-T MRI system, TR 8 msec, TE 3 msec, flip angle 12°, voxel size: isotropic 1 mm; TWH: GE Healthcare HDx 3-T scanner, TR 8 msec, TE 3 msec, flip angle 12°, voxel size: isotropic 1 mm) were first manually aligned to the AC-PC line in Slicer (https://www.slicer.org/). Subsequently, the mean DW image was nonlinearly registered to corresponding aligned T1-weighted images using ANTs (http://stnava.github.io/ANTs/). With this transformation applied, binarized deterministic fiber tracking maps of the PT and ML were overlaid on the AC-PC–aligned T1-weighted scan. Intersecting perpendicular lines were drawn in the AC-PC plane to mark the anterior border of the ML and medial border of the PT, as previously described.19 To generate a T-VIM coordinate, a fiducial was placed so that it was 3 mm equidistant from the borders of both the ML and PT (i.e., the ML defined the posterior boundary of the VIM, while the PT defined its lateral boundary; Fig. 1).19 Differences among T-VIM coordinates, planned indirect coordinates, and final indirect coordinates were statistically assessed using two-tailed paired sample t-tests.

FIG. 1.
FIG. 1.

T-VIM localization method. A: Representative PT (red) and ML (blue) fiber tracts are overlaid on a preoperative sagittal DW image in subject space. B: The same fiber tracts are visualized on a preoperative axial T1-weighted image in subject space at the level of the AC-PC. Inset: Intersecting perpendicular lines were placed along the anterior boundary of the ML and the medial boundary of the PT; subsequently, target coordinates for T-VIM were selected by placing a fiducial 3 mm equidistant from each line. Figure is available in color online only.

Tractography-Based Translation of Lesions

Thalamotomy lesions were manually delineated on axial 3D T1-weighted fast-spoiled gradient recalled (FSPGR) images obtained 1 day after the MRgFUS treatment.24,25 Right-sided lesion masks were flipped in the X-Y plane so that all lesions were left-lateralized. To compare spatial positioning of the final indirect target coordinates and the tractography-based target coordinates, each lesion was translated in subject space by the anteroposterior (AP) and mediolateral (M-L) difference between these two sets of coordinates for each patient (Fig. 2): AP translation = APtractography − APindirect, M-L translation = M-Ltractography − M-Lindirect. Thus, in this experimental model, each patient had two lesions: a nontranslated treatment lesion derived from final indirect targeting and a translated lesion that reflected the displacement of the treatment lesion toward the T-VIM. Nontranslated and translated lesion masks were nonlinearly transformed to Montreal Neurological Institute (MNI; Colin27) space using the ANIMAL algorithm.22 To assess for spatial differences, summation maps for both lesion groups were subsequently obtained using the MINC toolkit (http://bic-mni.github.io). Subsequently, these maps were overlaid on a computerized histology-derived thalamic atlas to visually compare their spatial distribution in relation to relevant thalamic nuclei.3 A Wilcoxon signed-rank test with continuity correction was also performed to statistically compare the location of the translated and nontranslated summation maps. The RMINC package (https://mouse-imaging-centre.github.io/RMINC/authors.html) was used for this analysis.

FIG. 2.
FIG. 2.

Lesion translation method. The process of displacing indirectly targeted treatment lesions toward T-VIM is visually depicted in consecutive axial images at the level of the AC-PC. Planned indirect targeting coordinates are calculated with reference to the PC and midcommissural point; these are subsequently adjusted based on intraoperative observations to give final indirect targeting coordinates, which are used to create a treatment lesion. Retrospective T-VIM is conducted with reference to the PT and ML. The AP and M-L difference between T-VIM coordinates and final indirectly targeted VIM coordinates is calculated and subsequently applied to the treatment lesion to “translate” it toward T-VIM. Xf = x-axis coordinate of final lesion; Xp = x-axis coordinate of planned lesion; Xt = x-axis coordinate of translated lesion; Xtv = x-axis coordinate of tractography-defined VIM target; Yf = y-axis coordinate of final lesion; Yp = y-axis coordinate of planned lesion; Yt = y-axis coordinate of translated lesion; Ytv = y-axis coordinate of tractography-defined VIM target. Figure is available in color online only.

Clinical Relevance of Tractography-Based Targeting: Overlap Analysis With Adverse Effect Areas

To explore the putative clinical relevance of the tractography-based targeting method, we compared translated and nontranslated lesion masks with respect to their overlap with previously published “adverse effects areas” in patients with sensory and motor adverse effects.2 We set a threshold value of 5, so that the resultant areas were 5 times more likely to be associated with an adverse effect if lesioned with MRgFUS. In patients who experienced either of these adverse events posttreatment, both translated and nontranslated lesion masks were assessed for overlap with the symptom-appropriate adverse effect map: lesions of patients with motor and/or sensory adverse effects were assessed for overlap with the motor and sensory adverse effect maps, respectively. Finally, we calculated the percentage overlap of each lesion with its corresponding adverse effect map, comparing the extent of overall overlap between the translated and nontranslated conditions using Wilcoxon signed-rank tests.

Results

Forty-three patients (36 males, 7 females; mean age 71.1 ± 8.9 years; age range 42–85 years) fulfilled the inclusion criteria and were thus included in the study. Of these patients, 39 had essential tremor and 4 had tremor-dominant Parkinson’s disease. Mean disease duration was 29.9 ± 17.9 years (range 5–61 years). Thirty-eight patients received left-sided FUS lesions, while 5 patients received right-sided lesions. In this cohort, 14 patients experienced acute posttreatment adverse effects; 5 of these patients had only sensory adverse effects, 6 had only motor adverse effects, and 3 had both sensory and motor adverse effects.

Tractography-Based Translation of Lesions and Overlap With Adverse Effects Areas

Overall, the summation map of the translated lesions was located more anterior and medial to that of the nontranslated lesions (Fig. 3). Specifically, T-VIM was found to be significantly anterior (by 2.18 mm, t = 7.2873, p < 0.01) and medial (by 1.82 mm, t = 4.5549, p < 0.01) to the final VIM coordinates (Table 1). Final target coordinates also significantly differed from planned indirect targeting coordinates in terms of anterior displacement (t = 2.1826, p = 0.0347), placing the T-VIM coordinates closer to the final than the planned indirect targeting coordinates. The summation maps of the nontranslated and translated lesions were also spatially distinct (V = 277130, p < 0.01, Wilcoxon signed-rank test). The translated summation map overlapped less with the ventral caudal thalamic nucleus and was further from the internal capsule than the nontranslated summation map. The maxima of the translated summation map also lay more squarely within the histology-derived VIM compared to the nontranslated summation map, whose maxima were situated posterior to the boundary of this nucleus (Fig. 3).

FIG. 3.
FIG. 3.

T-VIM–translated thalamotomy lesions are located anterior and medial to indirectly targeted lesions. Points of maximal value from thalamotomy lesion summation maps (A and B) are overlaid on a computerized histology-derived thalamic atlas3 displaying the ventro-oralis posterior nucleus (Vop; pink), VIM (yellow), and ventral caudal nucleus (VC; blue) in MNI (Colin27) space. The summation map of lesions displaced toward the T-VIM (green crosshairs) is anterior and medial compared with the summation map of the nontranslated lesions (red crosshairs), falling within the VIM. Figure is available in color online only.

TABLE 1.

VIM coordinates

CoordinatePlanned IndirectFinal IndirectT-VIM
Ant coordinates (distance from PC in mm)6.60 ± 0.746.90 ± 1.169.08 ± 1.96
Lat coordinates (distance from midline in mm)15.03 ± 0.7214.93 ± 1.2113.11 ± 2.23

Ant = anterior.

Values are expressed as the mean ± standard deviation.

Lesions translated toward the T-VIM were located further from the adverse effect areas and overlapped less with these areas (Figs. 4 and 5). In the sensory adverse effects cohort (n = 8), all 8 (100%) patients’ nontranslated lesion masks overlapped with the thresholded sensory adverse effect map, while only 4 (50%) patients’ lesions overlapped after they had been translated according to the tractography-based targeting. Percentage overlap was significantly lower for translated lesion masks (mean 6.1% ± 10.7%) than for nontranslated masks (mean 32.8% ± 28.3%; V = 36, p = 0.01; Fig. 4). In the cohort of patients with motor adverse effects, 4 (44.4%) of 9 patients’ lesion masks overlapped with the thresholded motor adverse effect map in both nontranslated and translated form. While the percentage overlap for translated lesion masks (mean 2.4 ± 4.9%) was decreased relative to that for nontranslated masks (mean 24.2 ± 34.1%), the difference was not statistically significant (V = 14, p = 0.11; Fig. 5).

FIG. 4.
FIG. 4.

Displacement of lesions toward the T-VIM decreases lesion overlap with areas associated with sensory adverse effects. A: An odds ratio map (red) displaying voxels associated with ≥ 5 times greater risk of sensory adverse effects is overlaid on a computerized histology-derived thalamic atlas.3 B: A representative thalamotomy lesion (blue) in a patient with postprocedural sensory adverse effects overlaps with this sensory adverse effect odds-ratio map (area of overlap: orange). C: Following displacement of the lesion toward patient-specific T-VIM coordinates (translated lesion: green), overlap with the sensory adverse effect odds ratio map (area of overlap: orange) is decreased. Figure is available in color online only.

FIG. 5.
FIG. 5.

Displacement of lesions toward the T-VIM decreases lesion overlap with areas associated with motor adverse effects. A: An odds ratio map (red) displaying voxels associated with ≥ 5 times greater risk of motor adverse effects is overlaid on a computerized histology-derived thalamic atlas.3 B: A representative thalamotomy lesion (blue) in a patient with postprocedural motor adverse effects overlaps with this motor adverse effect odds ratio map (area of overlap: orange). C: Following displacement of the lesion toward patient-specific T-VIM coordinates (translated lesion: green), overlap with the motor adverse effect odds ratio map is decreased. Figure is available in color online only.

Discussion

This study yielded two major findings: 1) the T-VIM coordinate is located anteromedial to the VIM as targeted by the indirect method, and 2) displacement of MRgFUS lesions toward the T-VIM shifts them away from—and decreases overlap with—zones shown to correspond to adverse effects. This latter result suggests that our tractography-based targeting method would lower the incidence of adverse effects and lead to an improved clinical outcome, reinforcing the relevance of the PT and ML to motor and sensory disturbances following MRgFUS thalamotomy, respectively.

We found that the T-VIM coordinates were significantly different from the conventional indirect coordinates. T-VIM coordinates were located more anterior and medial to VIM coordinates selected with conventional indirect targeting. The more anterior location of the T-VIM coordinates is consistent with earlier studies utilizing T-VIM,10,14,19 while its comparatively medial position has been previously (though not unanimously) observed.12 Although we were unable to directly compare T-VIM lesions with the actual, indirectly targeted lesions in terms of tremor suppression here, converging lines of evidence suggest that a more anterior location may constitute the preferable VIM target for tremor surgery. Consistent with prior MER validation of T-VIM,12 our translated lesion summation map lay within the VIM, as specified by a computerized histology-derived thalamic atlas, whereas the nontranslated summation map derived from indirectly targeted lesions fell posterior to the histological VIM on this atlas.3 Recent VIM DBS mapping work from our group revealed that the optimal zone of VIM stimulation for tremor lay in the anterior aspect of the VIM, close to the ventro-oralis posterior nucleus (Vop) border.13 A more anterior target may be superior given its close relationship with the location of the dentatorubrothalamic (DRT) tract,19 which is thought to play a key role in the cerebello-thalamo-cortical network. Additionally, a more anterior target could encompass a nexus between tremor-generating targets within the thalamus (VIM, ventro-oralis anterior nucleus [Voa], and Vop). This is in keeping with a previous finding that tremor cells are not only widespread within the VIM, but are also distributed more anteriorly in the Voa and Vop.9 Indeed, the same study reported better tremor control when DBS electrodes were used to stimulate both the VIM and Voa/Vop than when stimulation was applied to the VIM alone.

The T-VIM coordinates appeared to shift the lesions away from adverse effect zones. This is consistent with prior meta-analytical indications that tractography-based targeting approaches may improve procedure safety and therapeutic outcome in DBS and has potential value in MRgFUS thalamotomy.20,23 It is also concordant with a recent tractography-based MRgFUS targeting study that reported no motor or sensory adverse effects and a good clinical outcome with more anterior targeting.14 Indeed, recent and ongoing research attests to the potential value of tractography in guiding surgical interventions for tremor. These include reports on the clinical utility of diffusion tensor imaging techniques in the lesioning of Vop and VIM,11 Gamma Knife thalomotomy,6 and nonrigid frameless linear accelerator stereotactic radiothalomotomy.10 Given the high rates of sensory and motor complications of MRgFUS, though the majority are temporary, compared to more established forms of VIM thalamotomy and VIM DBS, tractography-guided methods appear to hold particular promise for refining surgical targeting and ameliorating adverse effect profiles for this procedure.5

The variation and relative positioning of planned and final indirect targeting coordinates in this study further strengthens a role for T-VIM. Variability between final and initial/planned coordinates with indirect targeting was previously seen in the MRgFUS randomized controlled trial, wherein final targets were shifted between 1.1 and 5.5 mm in 39 of 56 patients (albeit in an unspecified direction).5 The present study corroborated this observation, showing final indirect coordinates to be, overall, more anterior and medial to the initial planned coordinates and thus closer to T-VIM. This in turn suggests that intraoperative feedback (i.e., the observation of acute adverse effects and tremor improvement) favored an anteromedial displacement, bringing the final coordinates closer to T-VIM coordinates and providing additional support for the validity of this target.

Study Limitations

This study is a retrospective ad hoc analysis. It is limited by the assumption that translated thalamotomy lesions would retain the same basic size and configuration as the nontranslated (i.e., actual) lesions. It should also be acknowledged that the threshold of 5 used for the adverse effect maps in this paper is ultimately arbitrary and does not indicate statistical significance; it was a conservative threshold chosen because a 5-fold increase in the risk of adverse effects was thought to be clinically relevant. Finally, it should be noted that this study makes another assumption by equating less overlap between lesion masks and adverse effect odds ratio maps with the notion of fewer posttreatment adverse effects. While this logically follows from the idea of an adverse effect map, our results ultimately require validation through a prospective and preferably randomized trial that can assess the effectiveness and safety of tractography-based targeting in comparison to the conventional approach.

Conclusions

This study is, to our knowledge, the first imaging analysis of a novel tractography-based targeting method in the context of MRgFUS thalamotomy in a large cohort of tremor patients. Given that MRI is inherent to the MRgFUS procedure, it is logical that new neuroimaging-derived targeting techniques should be explored in an effort to improve clinical outcomes. Here, we demonstrated that delineation of the VIM based on the relative position of key white matter tracts resulted in more anterior and medially placed target coordinates, which appeared to better overlap with histology-derived VIM. Moreover, displacement of indirectly targeted lesions toward T-VIM tended to move them away from previously identified areas at higher risk for motor and sensory adverse effects, suggesting that tractography-based targeting may help to minimize the adverse effects of this procedure.

Acknowledgments

We thank Eugen Hlasny, Ruby Endre, and Maheleth Llinas for their assistance with this study.

Disclosures

Dr. Fasano is a consultant for AbbVie, Medtronic, Boston Scientific, Sunovion, Chiesi Farmaceutici, UCB, and Ipsen; sits on the advisory boards of AbbVie, Boston Scientific, and Ipsen; and has received honoraria from AbbVie, Medtronic, Boston Scientific, Sunovion, Chiesi Farmaceutici, UCB, and Ipsen and grant funding from the University of Toronto, the Weston Foundation, AbbVie, Medtronic, and Boston Scientific. Dr. Devenyi is a consultant for MIAC AG. Dr. Hynynen holds patents with and receives royalties from Brigham and Women’s Hospital. Dr. Lozano is a consultant for Medtronic, St. Jude, Insightec, and Boston Scientific.

Imaging data used in this paper include data from a cohort of patients who have been part of a study funded by Insightec. Dr. Hodaie or other research members have not had any industry support for this study, nor was there any specific funding for this imaging research.

Author Contributions

Conception and design: Hodaie, Ranjan, Elias, Boutet, Chakravarty, Kucharczyk, Schwartz, Lozano. Acquisition of data: Hodaie, Ranjan, Elias, Boutet, Chakravarty. Analysis and interpretation of data: Hodaie, Ranjan, Elias, Boutet, Zhong, Chu, Germann, Devenyi, Fasano, Hynynen, Lipsman, Hamani. Drafting the article: Ranjan, Elias. Critically revising the article: Hodaie, Boutet, Zhong, Chu, Germann, Devenyi, Chakravarty, Fasano, Hynynen, Lipsman, Hamani, Kucharczyk, Schwartz, Lozano. Reviewed submitted version of manuscript: Hodaie. Approved the final version of the manuscript on behalf of all authors: Hodaie. Statistical analysis: Ranjan, Elias. Administrative/technical/material support: Schwartz, Lozano. Study supervision: Hodaie.

References

  • 1

    Anthofer J, Steib K, Fellner C, Lange M, Brawanski A, Schlaier J: The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation. Acta Neurochir (Wien) 156:14971504, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Boutet A, Ranjan M, Zhong J, Germann J, Xu D, Schwartz ML, et al.: Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain 141:34053414, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Chakravarty MM, Bertrand G, Hodge CP, Sadikot AF, Collins DL: The creation of a brain atlas for image guided neurosurgery using serial histological data. Neuroimage 30:359376, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, et al.: A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med 369:640648, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, et al.: A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med 375:730739, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Gomes JG, Gorgulho AA, de Oliveira López A, Saraiva CW, Damiani LP, Pássaro AM, et al.: The role of diffusion tensor imaging tractography for Gamma Knife thalamotomy planning. J Neurosurg 125 (Suppl 1):129138, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Ilinsky IA, Kultas-Ilinsky K: Motor thalamic circuits in primates with emphasis on the area targeted in treatment of movement disorders. Mov Disord 17 (Suppl 3):S9S14, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Johansen-Berg H, Behrens TE, Sillery E, Ciccarelli O, Thompson AJ, Smith SM, et al.: Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. Cereb Cortex 15:3139, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Katayama Y, Kano T, Kobayashi K, Oshima H, Fukaya C, Yamamoto T: Difference in surgical strategies between thalamotomy and thalamic deep brain stimulation for tremor control. J Neurol 252 (Suppl 4):IV17IV22, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Kim W, Sharim J, Tenn S, Kaprealian T, Bordelon Y, Agazaryan N, et al.: Diffusion tractography imaging-guided frameless linear accelerator stereotactic radiosurgical thalamotomy for tremor: case report. J Neurosurg 128:215221, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Kincses ZT, Szabó N, Valálik I, Kopniczky Z, Dézsi L, Klivényi P, et al.: Target identification for stereotactic thalamotomy using diffusion tractography. PLoS One 7:e29969, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    King NKK, Krishna V, Basha D, Elias G, Sammartino F, Hodaie M, et al.: Microelectrode recording findings within the tractography-defined ventral intermediate nucleus. J Neurosurg 126:16691675, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    King NKK, Krishna V, Sammartino F, Bari A, Reddy GD, Hodaie M, et al.: Anatomic targeting of the optimal location for thalamic deep brain stimulation in patients with essential tremor. World Neurosurg 107:168174, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Krishna V, Sammartino F, Agrawal P, Changizi BK, Bourekas E, Knopp MV, et al.: Prospective tractography-based targeting for improved safety of focused ultrasound thalamotomy. Neurosurgery 84:160168, 2019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Leemans A, Jones DK: The B-matrix must be rotated when correcting for subject motion in DTI data. Magn Reson Med 61:13361349, 2009

  • 16

    Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, et al.: MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol 12:462468, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Papavassiliou E, Rau G, Heath S, Abosch A, Barbaro NM, Larson PS, et al.: Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. Neurosurgery 54:11201130, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Pilitsis JG, Metman LV, Toleikis JR, Hughes LE, Sani SB, Bakay RA: Factors involved in long-term efficacy of deep brain stimulation of the thalamus for essential tremor. J Neurosurg 109:640646, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Sammartino F, Krishna V, King NK, Lozano AM, Schwartz ML, Huang Y, et al.: Tractography-based ventral intermediate nucleus targeting: novel methodology and intraoperative validation. Mov Disord 31:12171225, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    See AAQ, King NKK: Improving surgical outcome using diffusion tensor imaging techniques in deep brain stimulation. Front Surg 4:54, 2017

  • 21

    Shih LC, LaFaver K, Lim C, Papavassiliou E, Tarsy D: Loss of benefit in VIM thalamic deep brain stimulation (DBS) for essential tremor (ET): how prevalent is it? Parkinsonism Relat Disord 19:676679, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Sprenger T, Seifert CL, Valet M, Andreou AP, Foerschler A, Zimmer C, et al.: Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping. Brain 135:25362545, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Tsolaki E, Downes A, Speier W, Elias WJ, Pouratian N: The potential value of probabilistic tractography-based for MR-guided focused ultrasound thalamotomy for essential tremor. Neuroimage Clin 17:10191027, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Vincent RD, Buckthought A, MacDonald D: MNI Display—Software for visualization and segmentation of surfaces and volumes. Montreal Neurological Institute (http://www.bic.mni.mcgill.ca/software/Display/Display.html) [Accessed August 1, 2019]

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Wintermark M, Druzgal J, Huss DS, Khaled MA, Monteith S, Raghavan P, et al.: Imaging findings in MR imaging-guided focused ultrasound treatment for patients with essential tremor. AJNR Am J Neuroradiol 35:891896, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand

Artist’s rendering showing the trajectories for the ipsilateral supracerebellar infratentorial (iSCIT), contralateral supracerebellar infratentorial (cSCIT), ipsilateral occipital transtentorial (iOCTT), and contralateral occipital transtentorial/falcine (cOCTF) approaches to the pulvinar. Also shown is a cadaveric view of the pulvinar via the cSCIT approach (inset). Artist: K. Larson. Used with permission from Barrow Neurological Institute, Phoenix, Arizona. See the article by Sun et al. (pp. 1172–1181).

  • FIG. 1.

    T-VIM localization method. A: Representative PT (red) and ML (blue) fiber tracts are overlaid on a preoperative sagittal DW image in subject space. B: The same fiber tracts are visualized on a preoperative axial T1-weighted image in subject space at the level of the AC-PC. Inset: Intersecting perpendicular lines were placed along the anterior boundary of the ML and the medial boundary of the PT; subsequently, target coordinates for T-VIM were selected by placing a fiducial 3 mm equidistant from each line. Figure is available in color online only.

  • FIG. 2.

    Lesion translation method. The process of displacing indirectly targeted treatment lesions toward T-VIM is visually depicted in consecutive axial images at the level of the AC-PC. Planned indirect targeting coordinates are calculated with reference to the PC and midcommissural point; these are subsequently adjusted based on intraoperative observations to give final indirect targeting coordinates, which are used to create a treatment lesion. Retrospective T-VIM is conducted with reference to the PT and ML. The AP and M-L difference between T-VIM coordinates and final indirectly targeted VIM coordinates is calculated and subsequently applied to the treatment lesion to “translate” it toward T-VIM. Xf = x-axis coordinate of final lesion; Xp = x-axis coordinate of planned lesion; Xt = x-axis coordinate of translated lesion; Xtv = x-axis coordinate of tractography-defined VIM target; Yf = y-axis coordinate of final lesion; Yp = y-axis coordinate of planned lesion; Yt = y-axis coordinate of translated lesion; Ytv = y-axis coordinate of tractography-defined VIM target. Figure is available in color online only.

  • FIG. 3.

    T-VIM–translated thalamotomy lesions are located anterior and medial to indirectly targeted lesions. Points of maximal value from thalamotomy lesion summation maps (A and B) are overlaid on a computerized histology-derived thalamic atlas3 displaying the ventro-oralis posterior nucleus (Vop; pink), VIM (yellow), and ventral caudal nucleus (VC; blue) in MNI (Colin27) space. The summation map of lesions displaced toward the T-VIM (green crosshairs) is anterior and medial compared with the summation map of the nontranslated lesions (red crosshairs), falling within the VIM. Figure is available in color online only.

  • FIG. 4.

    Displacement of lesions toward the T-VIM decreases lesion overlap with areas associated with sensory adverse effects. A: An odds ratio map (red) displaying voxels associated with ≥ 5 times greater risk of sensory adverse effects is overlaid on a computerized histology-derived thalamic atlas.3 B: A representative thalamotomy lesion (blue) in a patient with postprocedural sensory adverse effects overlaps with this sensory adverse effect odds-ratio map (area of overlap: orange). C: Following displacement of the lesion toward patient-specific T-VIM coordinates (translated lesion: green), overlap with the sensory adverse effect odds ratio map (area of overlap: orange) is decreased. Figure is available in color online only.

  • FIG. 5.

    Displacement of lesions toward the T-VIM decreases lesion overlap with areas associated with motor adverse effects. A: An odds ratio map (red) displaying voxels associated with ≥ 5 times greater risk of motor adverse effects is overlaid on a computerized histology-derived thalamic atlas.3 B: A representative thalamotomy lesion (blue) in a patient with postprocedural motor adverse effects overlaps with this motor adverse effect odds ratio map (area of overlap: orange). C: Following displacement of the lesion toward patient-specific T-VIM coordinates (translated lesion: green), overlap with the motor adverse effect odds ratio map is decreased. Figure is available in color online only.

  • 1

    Anthofer J, Steib K, Fellner C, Lange M, Brawanski A, Schlaier J: The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation. Acta Neurochir (Wien) 156:14971504, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Boutet A, Ranjan M, Zhong J, Germann J, Xu D, Schwartz ML, et al.: Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain 141:34053414, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Chakravarty MM, Bertrand G, Hodge CP, Sadikot AF, Collins DL: The creation of a brain atlas for image guided neurosurgery using serial histological data. Neuroimage 30:359376, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, et al.: A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med 369:640648, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, et al.: A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med 375:730739, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Gomes JG, Gorgulho AA, de Oliveira López A, Saraiva CW, Damiani LP, Pássaro AM, et al.: The role of diffusion tensor imaging tractography for Gamma Knife thalamotomy planning. J Neurosurg 125 (Suppl 1):129138, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Ilinsky IA, Kultas-Ilinsky K: Motor thalamic circuits in primates with emphasis on the area targeted in treatment of movement disorders. Mov Disord 17 (Suppl 3):S9S14, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Johansen-Berg H, Behrens TE, Sillery E, Ciccarelli O, Thompson AJ, Smith SM, et al.: Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. Cereb Cortex 15:3139, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Katayama Y, Kano T, Kobayashi K, Oshima H, Fukaya C, Yamamoto T: Difference in surgical strategies between thalamotomy and thalamic deep brain stimulation for tremor control. J Neurol 252 (Suppl 4):IV17IV22, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Kim W, Sharim J, Tenn S, Kaprealian T, Bordelon Y, Agazaryan N, et al.: Diffusion tractography imaging-guided frameless linear accelerator stereotactic radiosurgical thalamotomy for tremor: case report. J Neurosurg 128:215221, 2018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Kincses ZT, Szabó N, Valálik I, Kopniczky Z, Dézsi L, Klivényi P, et al.: Target identification for stereotactic thalamotomy using diffusion tractography. PLoS One 7:e29969, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    King NKK, Krishna V, Basha D, Elias G, Sammartino F, Hodaie M, et al.: Microelectrode recording findings within the tractography-defined ventral intermediate nucleus. J Neurosurg 126:16691675, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    King NKK, Krishna V, Sammartino F, Bari A, Reddy GD, Hodaie M, et al.: Anatomic targeting of the optimal location for thalamic deep brain stimulation in patients with essential tremor. World Neurosurg 107:168174, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Krishna V, Sammartino F, Agrawal P, Changizi BK, Bourekas E, Knopp MV, et al.: Prospective tractography-based targeting for improved safety of focused ultrasound thalamotomy. Neurosurgery 84:160168, 2019

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Leemans A, Jones DK: The B-matrix must be rotated when correcting for subject motion in DTI data. Magn Reson Med 61:13361349, 2009

  • 16

    Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, et al.: MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol 12:462468, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Papavassiliou E, Rau G, Heath S, Abosch A, Barbaro NM, Larson PS, et al.: Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. Neurosurgery 54:11201130, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Pilitsis JG, Metman LV, Toleikis JR, Hughes LE, Sani SB, Bakay RA: Factors involved in long-term efficacy of deep brain stimulation of the thalamus for essential tremor. J Neurosurg 109:640646, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Sammartino F, Krishna V, King NK, Lozano AM, Schwartz ML, Huang Y, et al.: Tractography-based ventral intermediate nucleus targeting: novel methodology and intraoperative validation. Mov Disord 31:12171225, 2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    See AAQ, King NKK: Improving surgical outcome using diffusion tensor imaging techniques in deep brain stimulation. Front Surg 4:54, 2017

  • 21

    Shih LC, LaFaver K, Lim C, Papavassiliou E, Tarsy D: Loss of benefit in VIM thalamic deep brain stimulation (DBS) for essential tremor (ET): how prevalent is it? Parkinsonism Relat Disord 19:676679, 2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Sprenger T, Seifert CL, Valet M, Andreou AP, Foerschler A, Zimmer C, et al.: Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping. Brain 135:25362545, 2012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Tsolaki E, Downes A, Speier W, Elias WJ, Pouratian N: The potential value of probabilistic tractography-based for MR-guided focused ultrasound thalamotomy for essential tremor. Neuroimage Clin 17:10191027, 2017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Vincent RD, Buckthought A, MacDonald D: MNI Display—Software for visualization and segmentation of surfaces and volumes. Montreal Neurological Institute (http://www.bic.mni.mcgill.ca/software/Display/Display.html) [Accessed August 1, 2019]

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Wintermark M, Druzgal J, Huss DS, Khaled MA, Monteith S, Raghavan P, et al.: Imaging findings in MR imaging-guided focused ultrasound treatment for patients with essential tremor. AJNR Am J Neuroradiol 35:891896, 2014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 2735 387 0
Full Text Views 544 154 40
PDF Downloads 583 149 28
EPUB Downloads 0 0 0