Huan Wang1, Youqiu Xie2, Ling Weng1, Qing Ma2, Ling Zhao1, Ronghao Yu2, Miao Zhong1, Xiaoyan Wu1, and Ruiwang Huang1
1Center for the Study of Applied Psychology, Guangdong Key Laboratory of Mental Health and Cognitive Science, School of Psychology, South China Normal University, GuangZhou, China, People's Republic of, 2Coma research group and coma recovery unit, neuroscience institute, guangzhou general hospital of Guangzhou command, GuangZhou, China, People's Republic of
Synopsis
What we did was to use the tract-based spatial
statistics (TBSS) approach to examine the changes of diffusion parameters in whole
brain white matter of DOC patients relative to healthy controls, and to detect
the correlation between the diffusion parameters of white matters and clinical
variables.Introduction
The patients
with disorders of consciousness (DOC) can be divided
into vegetable state (VS), minimally conscious state (MCS). The aetiology of
these clinical outcomes was varied and there were high rate of misdiagnosis. Diffusion
tensor imaging (DTI) is a non-invasive technique to characterize the
microstructures of brain tissue and brain white matter distributions[1, 2]. Previous DTI studies
suggested that white matter microstructures in subcortical, thalamus, and
brainstem were impaired in VS patients[3, 4]. However, few
studies reported changes of brain white matter skeleton in DOC patients. In
this study, we attempted to use the tract-based spatial statistics (TBSS)
approach to examine the changes of diffusion parameters in whole brain white
matter of DOC patients relative to healthy controls, and to detect the
correlation between the diffusion parameters of white matters and clinical
variables.
Methods
Eighteen DOC patients (9VS/ 9MCS) of varying
aetiology (11M/ 7F) were recruited from the Coma Recovery
Unit, Centre for Hyperbaric Oxygen and Neurorehabilitaiton, Guangzhou
Liuhuaqiao Hospital. The VS and MCS patients were diagnosed using the Coma
Recovery Scale-Revised (CRS-R). We also enrolled 18 age- and gender-matched
healthy subjects (10M/ 8F) as the controls. The protocols were approved by the
Institutional Review Board of Guangzhou Liuhuaqiao Hospital. Written informed consent
was obtained from each patient.
All MR data were acquired on a 3T GE MRI scanner.
DTI data were obtained using a spin-echo diffusion-weighted EPI sequence: 30
volumes, b=1000s/mm2 and 3
b0, TR/TE=17000/85.9ms, matrix
= 256×256, FOV = 240mm×240mm, slice thickness = 2.4mm without gap, and 60 axial slices
covering the whole brain. The T1-weighted 3D images were acquired using 3D
FSPGR sequence: TR/TE=8.8/3.5ms, FOV=240mm×240mm,
matrix size=256×256, thickness=1mm,
176 sagittal slices.
DTI data were
processed with FSL package. First, all images underwent eddy current distortion
correction and then fitted a tensor model. Thus, we obtained the brain maps of
fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial
diffusivity (RD) for each subject. Second, we performed TBSS analysis on the
whole brain FA maps across all subjects with the FSL/FDT[5]. For example,
all FA images across subjects were co-registered to the FMRIB-58 FA template,
and were averaged to generate a study-specific FA map with nonlinear
coregistration. We created the mean FA skeleton for the present study. Third, the
FA map of each subject was projected onto the mean FA skeleton. We conducted
voxel-wised analysis with FA>0.2, removed covariates with GLM and carried
out a non-parametric permutation test (5,000 repetitions). The same procedures
were also conducted on the brain maps of MD, AD, and RD, respectively. The
voxel-based threshold (p<0.05) was
applied with multi-comparison correction (TFCE). Meanwhile, the ROI-based
calculation was carried out to extract FA values that show differences in the
white matters of each subject. Last, FA values of all 18 patients were used to
carry out correlation analyses with the scores of CRS-R.
Results
Fig. 1 shows brain white
matter with significant differences in FA, MD, AD, and RD maps between the DOC
and HC groups (p<0.001, TFCE-corrected).
We found the DOC group showed significantly decreased FA and AD, but increased
MD and RD, in the tracts of corpus callosum, forceps minor and bilateral
fronto-occipital fasciculus (Table 1). Meanwhile, we also detected no
difference in FA values between MCS and VS (p = 0.0761). The results
from the ROI-based correlation analyses revealed significant correlation (p < 0.05, corrected) between CRS-R
scores of auditory, vision, motor and FA values of each DOC patients’ different
white matters (Fig. 2).
Conclusion
Our study
revealed the alteration of brain white matter in the projection fibers,
association fibers, and commissural fibers were correlated with the onset of
DOC patients.Our findings may be useful for studying the pathophysiology,
progression and treatment of DOC patients.
Acknowledgements
This work was partly supported by the funding from the National Natural Science Foundation of China (Grant numbers: 81371535 and 81271548), and Guangdong Provincial Natural Science Foundation of China (Program No. 2014A030313233).References
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