Chih-Chien Tsai1, Chia-Ling Chen2,3, Yao-Liang Chen4, Jur-Shan Cheng5, Sung-han Lin6, and Jiun-Jie Wang1,6,7
1Healthy Aging Research Center, Chang-Gung University, TaoYuan, Taiwan, 2Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, TaoYuan, Taiwan, 3Graduate Institute of Early Intervention, College of Medicine, Chang Gung University, TaoYuan, Taiwan, 4Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan, 5Clinical Informatics and Medical Statistics Research Center, Chang-Gung University, TaoYuan, Taiwan, 6Department of Medical Imaging and Radiological Sciences, Chang Gung University, TaoYuan, Taiwan, 7Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, TaoYuan, Taiwan
Synopsis
Disruption to white matter pathways is an important
contributor to the pathogenesis of cerebral palsy but fail to delineate white
matter tracts with lesions precisely with conventional magnetic resonance
imaging. Fixel-based analysis, which has recently emerged as a useful
fiber-specific tool for examining white matter structure, was used in this
study. Reductions of fixel-based
metrics in patients with cerebral palsy are represented in the corpus callosum, superior/posterior thalamic
radiation, optic radiation, superior longitudinal fasciculus, and cingulum with
corresponding direction of fiber tract. By using fixel-based analysis, this
study described the white matter differences during development in patients
with cerebral palsy.
INTRODUCTION
Spastic cerebral palsy is the most
common motor disease and affects the movement, posture and life quality in
children1. The
subtype of spastic cerebral palsy, which included unilateral spastic cerebral
palsy (hemiplegia) and bilateral
spastic cerebral palsy
(diplegia and quadriplegia), are observed with white matter lesion in
pathological studies2, 3. The most common patterns of white matter lesion were
periventricular leukomalacia, which exists irregular outlines of the trigone
and body of the lateral ventricle with ventriculomegaly from magnetic resonance
imaging4. However, conventional magnetic resonance imaging had
limitations and often failed to delineate white matter tracts with lesions
precisely 1, 5. Studies also used diffusion tensor imaging to reveal white matter
lesions. The measurement of diffusion tensor
imaging may be potentially
affected by 1)
complex of white matter fiber configurations (e.g., crossing)6, 7, and 2)
an imprecise representations and projections
with inadequate
modeling8 and 3) tensor properties from fractional
anisotropic and mean diffusivity did not provide additional
information about fiber orientation. To circumvent these issues,
fixel-based analysis was proposed to investigate white matter changes7. In this cross-sectional study, we used fixel-based analysis to
investigate white matter differences between patients with cerebral
palsy and typically developing
children.METHODS
The study protocol complied with the tenets of the
Declaration of Helsinki and was approved by the Institutional Review Board. All
participants gave their written informed consent. A total of 34 children with cerebral palsy (19
boys and 15 girls; mean age: 11.5±3.2 years), and 27 sex-balanced typically developing children (14 boys
and 13 girls; mean age: 17.5±3.6 years)
were recruited. Children diagnosed with
cerebral palsy and aged 3-20 years met the inclusion criteria.
MRI was performed with a 3T MR750
scanner using a 12-channel head matrix coil (GE Medical Systems, Milwaukee, WI).
Diffusion-weighted images were acquired using a spin-echo echo-planar-imaging
sequence with repetition time/echo time/slice thickness = 4000 ms/103.5 ms/ mm,
matrix size = 96 × 96, and field of view = 192 × 192 mm2, 40 slices
which covered the whole brain down to the cerebellum. Diffusion-weighted
gradients were applied along 30 non-collinear directions using b-values of 0,
500, 1000, 1500, 2000, and 2500 s/mm2.
FBA was performed by MRtrix3 (https://github.com/MRtrix3/mrtrix3) following the recommended procedures9,
including preprocessing, estimation for distribution of fiber orientations,
study-specific template establishment, and calculation of fixel-based metric,
which included fiber density (FD), fiber bundle cross-section (FC), and combined measure by multiplying FD and FC (FDC). Statistical analyses of the image were performed with the code fixelcfestat in MRtrix3. Using age and sex as covariates, comparisons of
metrics between patients with cerebral palsy and typically developing children
were performed. A FWE-corrected p < 0.05 with a cluster-extent-based threshold of 10 or more
voxels was considered statistically significant10.RESULTS
The difference of white matter development
between children with cerebral palsy and
typically developing children
was shown in Figure 1. Compared to the typically developing children, patients
with cerebral palsy reduced in FC and FDC predominantly in the anterior and
posterior part of the corpus callosum, commissural area, posterior limb of internal
capsule, superior and posterior thalamic radiation, cingulum fiber, optic
radiation, and superior longitudinal fasciculus. In contrast, FD reductions
were identified in the posterior part of the corpus callosum, posterior thalamic
radiation, fornix, and cingulum fiber. To clearly illustrate the differences
between both groups, significant variations along fixels were plotted in axial
slices (Fig. 2).
To shed more light on the
differences between patients with cerebral palsy and typically developing children, significant reduced FDC were displayed in representative slices with
information of tract direction (Fig. 3). The FDC reduced regions were displayed
in an axial view (panels a and b) – including the anterior and posterior of the corpus callosum, optic radiation, posterior thalamic radiation, and posterior
limb of internal capsule. The FDC changes in a representative coronal slice of
the corticospinal tract and commissural area (panel c and d) and in a
representative sagittal view of the superior thalamic radiation, superior
longitudinal fasciculus, cingulum and corpus callosum (panel e-h) are depicted.DISCUSSION
The major
reductions in white matter were observed in the anterior, posterior corpus
callosum, and corticospinal tract, consistent with previous knowledge of the
spatial distribution characteristics of white matter lesions by voxel-based
analysis or tract-based spatial statistics in patients with cerebral
palsy11, 12. Reductions of FC and FDC in the superior,
posterior thalamic radiation and cingulum were also represented, indicated the
importance of thalamus, cingulate gyrus for relaying information between
different subcortical and cerebral cortex13. Besides, reductions of FC and FDC
in optic radiation also were consistent with deficiency of visual-motor
integration in patients with cerebral palsy14. These observations suggested that white matter development might be related to axonal lesions, which was subsequently followed by
fiber bundle atrophy9.CONCLUSION
This study provided a thorough fixel-based metrics
of white matter differences in patients with cerebral palsy and typically
developing children with new evidence of FD, FC, and FDC, which helped to
clarify the influence of cerebral palsy on the development of specific white
matter regions.Acknowledgements
No acknowledgement found.References
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