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Alexey V. Dimov, Ajay Gupta, Brian H. Kopell, and Yi Wang

OBJECTIVE

Faithful depiction of the subthalamic nucleus (STN) is critical for planning deep brain stimulation (DBS) surgery in patients with Parkinson’s disease (PD). Quantitative susceptibility mapping (QSM) has been shown to be superior to traditional T2-weighted spin echo imaging (T2w). The aim of the study was to describe submillimeter QSM for preoperative imaging of the STN in planning of DBS.

METHODS

Seven healthy volunteers were included in this study. T2w and QSM were obtained for all healthy volunteers, and images of different resolutions were reconstructed. Image quality and visibility of STN anatomical features were analyzed by a radiologist using a 5-point scale, and contrast properties of the STN and surrounding tissue were calculated. Additionally, data from 10 retrospectively and randomly selected PD patients who underwent 3-T MRI for DBS were analyzed for STN size and susceptibility gradient measurements.

RESULTS

Higher contrast-to-noise ratio (CNR) values were observed in both high-resolution and low-resolution QSM images. Inter-resolution comparison demonstrated improvement in CNR for QSM, but not for T2w images. QSM provided higher inter-quadrant contrast ratios (CR) within the STN, and depicted a gradient in the distribution of susceptibility sources not visible in T2w images.

CONCLUSIONS

For 3-T MRI, submillimeter QSM provides accurate delineation of the functional and anatomical STN features for DBS targeting.

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Alexander G. Chartrain, Ahmed J. Awad, Jonathan J. Rasouli, Robert J. Rothrock, and Brian H. Kopell

A 59-year-old woman with a 30-year history of essential tremor refractory to medical therapy underwent staged deep brain stimulation of the ventralis intermedius nucleus of the thalamus (VIM). Left-sided lead placement was performed first. Once in the operating room, microelectrode recording (MER) was performed to confirm the appropriate trajectory and identify the VIM border with the ventralis caudalis nucleus. MER was repeated after repositioning 2 mm anteriorly to reduce the likelihood of stimulation-induced paresthesias. Physical examination prior to permanent lead placement demonstrated micro-lesion effect, suggesting optimal trajectory. After implantation of the permanent lead, physical examination showed excellent results.

The video can be found here: https://youtu.be/nn3KRdmRCZ4.

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Weiyuan Huang, Richard Ogbuji, Liangdong Zhou, Lingfei Guo, Yi Wang, and Brian H. Kopell

OBJECTIVE

The objective of this study was to investigate the correlation between the quantitative susceptibility mapping (QSM) signal gradient of the subthalamic nucleus (STN) and motor impairment in patients with Parkinson’s disease (PD).

METHODS

All PD patients who had undergone QSM MRI for presurgical deep brain stimulation (DBS) planning were eligible for inclusion in this study. The entire STN and its three functional subdivisions, as well as the adjacent white matter (WM), were segmented and measured. The QSM value difference between the entire STN and adjacent WM (STN-WM), between the limbic and associative regions of the STN (L-A), and between the associative and motor regions of the STN (A-M) were obtained as measures of gradient and were input into an unsupervised k-means clustering algorithm to automatically categorize the overall boundary distinctness between the STN and adjacent WM and between STN subdivisions (gradient blur [GB] and gradient sharp [GS] groups). Statistical tests were performed to compare clinical and image measurements for discrimination between GB and GS groups.

RESULTS

Of the 39 study patients, 19 were categorized into the GB group and 20 into the GS group, based on quantitative cluster analysis. The GB group had a significantly higher presurgical off-medication Unified Parkinson’s Disease Rating Scale Part III score (51.289 ± 20.741) than the GS group (38.5 ± 16.028; p = 0.037). The GB group had significantly higher QSM values for the STN and its three subdivisions and adjacent WM than those for the GS group (p < 0.01). The GB group also demonstrated a significantly higher STN-WM gradient in the right STN (p = 0.01). The GB group demonstrated a significantly lower L-A gradient in both the left and the right STN (p < 0.02).

CONCLUSIONS

Advancing PD with more severe motor impairment leads to more iron deposition in the STN and adjacent WM, as shown in the QSM signal. Loss of the STN inner QSM signal gradient should be considered as an image marker for more severe motor impairment in PD patients.

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Alexey Dimov, Wahaj Patel, Yihao Yao, Yi Wang, Rafael O’Halloran, and Brian H. Kopell

OBJECTIVE

The objective of this study was to investigate the relationship between iron and white matter connectivity in the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) of the STN for treatment of Parkinson’s disease.

METHODS

Nine Parkinson’s disease patients underwent preoperative 3T MRI imaging which included acquisition of T1-weighted anatomical images along with diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM). MR tractography was performed for the seed voxels located within the STN, and the correlations between normalized QSM values and the STN’s connectivity to a set of a priori chosen regions of interest were assessed.

RESULTS

A strong negative correlation was found between STN connectivity and QSM intensity for the thalamus, premotor, motor, and sensory regions, while a strong positive correlation was found for frontal, putamen, and brain stem areas.

CONCLUSIONS

Quantitative susceptibility mapping not only accurately delineates the STN borders but is also able to provide functional information about the STN functional subdivisions. The observed iron-to-connectivity correlation patterns may aid in planning DBS surgery to avoid unwanted side effects associated with DBS.

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Katherine Leaver, Aaron Viser, Brian H. Kopell, Roberto A. Ortega, Joan Miravite, Michael S. Okun, Sonya Elango, Deborah Raymond, Susan B. Bressman, Rachel Saunders-Pullman, and Marta San Luciano

OBJECTIVE

The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD).

METHODS

The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson’s Disease Rating Scale–part III) and medication usage were also assessed pre- and postoperatively.

RESULTS

Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group.

CONCLUSIONS

The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.