Nguyen Thanh Thao1, Chih-Chien Tsai2, Yao-Liang Chen3, Jur-Shan Cheng4, Chin-Song Lu5, Yi-Hsin Weng5, Sung-han Lin4, Po-Yuan Chen4, and Jiun-Jie Wang6
1Department of Radiology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam, 2Healthy Aging Research Center, Chang-Gung University, TaoYuan, Taiwan, 3Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan, 4Chang-Gung University, TaoYuan, Taiwan, 5Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital, Linkou Branch, TaoYuan, Taiwan, 6Department of Medical Imaging and Radiological Sciences, Chang-Gung University, TaoYuan, Taiwan
Synopsis
White matter degeneration have been
attributed to the motor and non-motor symptoms of Parkinson’s disease and
atypical parkinsonism. Our study shows different pattern of white matter
changes in multiple system atrophy and progressive supranuclear palsy compared
to Parkinson’s disease. Furthermore, different affected areas of white matter changes
were found among atypical parkinsonism. The
involved regions are consistent with the understanding of the pathogenesis of
the diseases. Our result proves that fixel based
analysis is a robust technique to study white matter degeneration in PD and atypical
parkinsonism.
Introduction
Parkinsonism is a neurological
disorder characterized by the presence of resting tremor, rigidity,
bradykinesia/akinesia and postural instability1. The most common
cause of Parkinsonism is the neurodegenerative
Parkinson's disease (PD). However, parkinsonism can be
caused by various conditions, including at least multiple
system atrophy (MSA) and progressive supranuclear palsy (PSP)2. These atypical parkinsonism usually show more rapid functional deterioration
than the neurodegenerative PD2. In addition, white matter degeneration might have been involved in the
motor and non-motor symptoms of the disorders3–7.
Fixel-based analysis is a new
approach using higher order
diffusion model to compute fiber orientation density function8. It allows the characterization of
the micro- and macrostructural environment from single fiber population within each
voxel, even with more than one fiber bundles. The aim of this
study was to investigate the white matter changes in a cohort of PD, MSA and PSP
patients by using fixel-based approach.Materials and Methods
Patients
The study has been
approved by the institutional review board. 53 patients diagnosed with PD
(Male/Female = 29/24, mean age = 65.06±5.51 year old), 47 with MSA (Male/Female
= 20/27, mean age = 63.00±7.19 year old) and 50 with PSP (Male/Female = 20/30,
mean age = 65.96±3.14 year old) were recruited. The diagnosis was made
according to established criteria for
PD9, MSA10 and PSP11. All patients were
evaluated using Modified Hoehn and Yahr Staging12
and the motor subscale of Unifed
Parkinson Disease Rating Scale13.
Data
acquisition
Diffusion
weighted images were acquired at a 3.0 Tesla
scanner (Trio
Magnetom; Siemens, Erlangen, Germany) using a
12-channel head coil with a diffusion-sensitive
spin-echo EPI sequence. Images of
diffusion weighting of b = 1,000 s/mm2 were acquired along 61 non-collinear directions and with a voxel size of 2x2x2 mm3 (89 participants), or alternatively along 30 directions with 2x2x3 mm3 (65 participants).
Image
Processing
Fixel-based analysis was performed
using MRtrix3 following the procedures by Raffelt et al8,14. Preprocessing steps include
Marchenko-Pastur principal component analysis, denoising15, Gibbs ringing removal16, motion and distortion correction17, bias field correction18. Fiber orientations distribution
(FOD) in each voxel was estimated using multi-tissue constrained spherical deconvolution19.
A study-specific template was created by spatial
normalization in all subjects using symmetric
diffeomorphic non-linear transformation FOD-based registration. Fiber
density and cross section (FDC) within each voxel was created by multiplying two
fixel derived index: Fiber density (FD)8 and fiber
bundle cross-section (FC).
Statistical
Analysis
Statistical
analysis for demographic differences was done by using SPSS (IBM, Armonk, NY,
USA). Differences in FDC between groups were calculated using non-parametric permutation testing and
connectivity-based fixel enhancement as implemented in
MRTrix3, with age, sex, and imaging parameters as covatiates14. A threshold of family-wise error -corrected p < 0.05 and a cluster-extent of 10
or more voxels was considered as statistically significant20.Results
Figure 1 showed the changes in FDC from PSP when compared to that in
patients with PD. In PSP group, reduced FDC was identified in centrum
semiovale, corona radiata, commissural fibers of the body of corpus callosum,
corticospinal tract, posterior limbs of internal capsule, cerebral peduncles,
midbrain and superior cerebellar peduncles. The white matter changes were
symmetrical both in the supratentorial and infratentorial compartments. Figure 2 highlighted the changes in bilateral corona radiata
(dashed arrows), commissural fibers (arrow head) and superior cerebellar
peduncles (black arrows).
Figure 3 showed the changes in FDC from MSA group
when compared to that in patients with PD. Reduced FDC was noticed in centrum
semiovale, corona radiata, corticospinal tract, posterior limbs of internal
capsule, cerebral peduncles, midbrain, pons, superior and middle cerebellar
peduncles and the arbor viate. It was noticed that the left part of centrum
semiovale, corona radiata and middle cerebellar peduncles were more affected
than the right side.
Figure 4
highlighted the reduction in
posterior limbs of internal capsule (black arrows), cerebral peduncles (dash
arrows), middle cerebellar peduncles (white arrow head).
The difference of FDC between
MSA and PSP was shown in Figure 5. Reduced
FDC in patients with PSP was found in bilateral corona radiata and body of the
corpus callosum (Upper Row). In contrast, reduced FDC in
MSA group was identified in bilateral medial lemniscus and in the left middle
cerebellar peduncles (Bottom Row).Discussions
The study proposed to
assess the white matter changes in three different types of patients with
parkinsonism by using fixel based analysis. The result showed profound white
matter damage in patients with MSA and PSP when compared to that in PD21. The involved
regions are consistent with the current understanding of the disease’s pathogenesis.
Noticeably, the white matter degeneration was significant in the middle
cerebellar peduncles in MSA patients when compared to that in PSP. In contrast,
fixel based analysis identified profound alteration in centrum semiovale in PSP
patients.
Our study showed that fixel-based analysis can provide a
comprehensive characterization of the white matter changes in patients with PD,
MSA and PSP. It is a robust technique to study which can be sensitive to the underlying
changes occurred in the microenvironment of white matter in Parkinson’s disease
and in atypical Parkinsonism.Acknowledgements
No acknowledgement found.References
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