Synopsis
Lead-DBS toolbox is used to segment globus pallidus internal,
globus pallidus external, subthalamic nucleus and red nucleus, all of which are
structures not automatically segmented by popular toolboxes such as FSL and
Freesurfer. In addition, FSL's diffusion toolbox was used to generate
probabilistic tractography between each segmented structure as well as compare
the level of connectivity between each segmented structure.
Introduction
Deep brain structures have shown to be effective targets of
deep brain stimulation (DBS) in treatment for Parkinson's Disease1. Therefore,
segmentation of deep brain structures is important in observing the effects of
Parkinson's, as well as providing accurate location of deep brain stimulation
targets. However, common automatic segmentation toolboxes such as the FMRIB
Software Library (FSL) and Freesurfer are unable to segment certain deep brain
structures involved in Parkinson's disease and treatment. In this study, we
utilize Lead-DBS toolbox2 to segment globus pallidus internal (GPi),
globus pallidus external (GPe),
subthalamic nucleus (STN) and red nucleus (RN). In addition, we use PROBTRACKX from the
FMRIB software library (FSL) diffusion toolkit to generate and compare
probabilistic tractography between each segmented structure3.Methods
For Lead-DBS structural segmentation, we used 3T MRI 3D-T1
weighted (TR = 2400 ms, TE = 2.14 ms, Flip Angle = 8 deg, Voxel Size = 0.7 mm
isotropic, BW = 210 Hz/Px, Acquisition Time = 7 min 40 sec), 3D-T2 weighted (TR
= 3200 ms, TE = 565 ms, Voxel Size = 0.7 mm isotropic, BW = 744 Hz/Px,
Acquisition Time = 8 min 24 sec) and diffusion MRI images (TR = 5520 ms, TE = 89.5
ms, Flip Angle = 78 deg, Slice Thickness = 1.25 mm, 111 slices, Multiband = 3,
Echo Spacing = 0.78 ms, BW = 1488 Hz/Px, b-values = 1000, 2000, and 3000 s/mm2)
of 4 females with the age range 26~35,
mean age 30.5 years (std = 3.2 years), obtained from Human Connectome Project
(HCP), 'WU-Minn HCP Data – 1200 subjects'4. All T1, T2 and diffusion
data were preprocessed using the HCP preprocessing pipeline5. Lead-DBS
segmentation was done using MAGeT Brain-like segmentation approach6,
which began with the segmentation of STN, GPi, GPe, RN in each subject using ANTs7.
Subsequently, each warps and segmentations generated from previous segmentation
were aggregated to provide additional information on the anatomical variance of
segmented subjects, which were used to re-segment each subject. The segmented
structures were overlaid on top of T2 images, where intensities of segmentation
targets are visible, to check for accuracy as shown in Figure 1A. Each segmented
structure was registered to its respective subject's diffusion MRI data, which were already preprocessed using eddy correction8 and BEDPOSTX9.
Then probabilistic tractography of each registered structure and between
registered structures were generated through PROBTRACKX10. The
number of fiber tracks generated by each subject were averaged, and percentages
were generated by dividing the totals of fibers that stemmed from each seed
structure. Results
Figure 1B
shows the 4 regions segmented by Lead-DBS. Each segmented structure that were
overlaid on top of T2 images for validation matched the intensities of
segmentation targets, confirming that segmentation was mainly successful. Table
1 shows the mean volumes of the segmented structures (A) and the results of waypoint
connectivity mapping between registered structures (B and C). We found that most of the fibers
that were generated were between GPe and GPi, with the least amount being
generated between GPi and RN. The number of fibers generated between left and
left, left and right, right and left, right and right segmented structures were
used to generate a connectivity matrix as shown in Figure 2. 3D and 2D representations of
fibers generated by PROBTRACKX are shown in Figure 3 and Figure 4. Discussion
Using Lead-DBS, we were able to successfully segment globus
pallidus internal, globus pallidus external, subthalamic nucleus and red
nucleus, and validate each segmentation through visual inspection. As such, we
predict that there will be an improved consistency when preparing DBS treatment
or comparing results of DBS treatment on the segmented structures by using
Lead-DBS to segment structures. Previous studies have shown that deep brain
stimulation of subthalamic nucleus had an increase in connectivity strength of
surrounding white matter tracts11. Other studies have shown that
direct deep brain stimulation of the tractography linking the basal ganglia
have shown improvements in treatment of Parkinson's disease12.
Therefore, we believe that the use of Lead-DBS to generate masks needed to
study the effects of DBS on tractography that pass through target structures should
improve the consistency of results. Conclusion
Our study shows that Lead-DBS was able to accurately segment
the four structures in each one of our HCP patients. In addition, we showed
that we can successfully generate probabilistic tractography between each
segmented structure using FSL's PROBTRACKX. Results show that there is
potential in using Lead-DBS to study effects of Parkinson's and Parkinson's
treatment on GPe, GPi, RN and STN, as well as the white matter tracts that pass
through them. Acknowledgements
This research was supported by
Brain Research Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Science and ICT (NRF-2017M3C7A1044367).References
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