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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Spatially heterogeneous T1w/T2w ratio alterations in relapsing-remitting multiple sclerosis: associations with
Xiaoshuang Ru1, Xuesong Li1, Shilong Zhao2
1Department of Radiology, Central Hospital of Dalian University of Technology, No. 826 Xinan Rd, Shahekou District, Dalian, Liaoning, 116033, China.
Objective:
The T1w/T2w ratio has been proposed as a feasible MRI biomarker reflecting tissue microstructural integrity. This study investigated its alterations across brain tissue types and regions in relapsing-remitting MS (RRMS) and its association with cognition and disability.
Methods:
72 RRMS patients and 70 matched healthy controls underwent neuropsychological testing and EDSS assessment. T1w/T2w ratio mapping was performed using MRTool. Mean ratio values were extracted from cortical GM, deep GM, WMH lesions, perilesional WM, and NAWM. Regional analyses used the JHU-ICBM-DTI-81 WM, Desikan-Killiany cortical, and Harvard-Oxford subcortical atlases. Lesion voxels were excluded from ROI averages. Between-group differences were assessed, and multiple linear regressions examined associations with EDSS and cognitive Z-scores, adjusting for demographics, disease covariates, lesion burden, and TIV, with FDR correction.
Results:
Compared to the controls, RRMS patients showed significantly lower T1w/T2w ratios in WMH lesions (p < 0.001), perilesional WM (p = 0.029), bilateral caudate (p = 0.025), fornix, sagittal stratum, and stria terminalis (all FDR-corrected p < 0.01), but higher ratios in the putamen, pallidum, accumbens (p < 0.05), cerebral peduncle, and anterior/posterior limb of internal capsule (p < 0.001). Learning and memory performance (CVLT-III, BVMT-R) was positively associated with T1w/T2w ratio in the left entorhinal cortex, bilateral caudate, and lesional segments of the left posterior thalamic radiation and sagittal stratum (β = 1.397-3.505, all FDR-corrected p < 0.05).
Conclusion:
The T1w/T2w ratio demonstrates spatially heterogeneous alterations across brain regions in RRMS, reflecting underlying pathological complexity and may serve as a promising neuroimaging biomarker for cognitive impairment.
Insights
The T1w/T2w ratio, an MRI biomarker, shows varied changes in brain regions of relapsing-remitting MS (RRMS) patients. These alterations correlate with cognitive function, suggesting its potential for assessing MS-related cognitive impairment.
Area of Science:
- Neuroimaging
- Neurology
- Biomarker Discovery
Background:
- The T1w/T2w ratio is a proposed MRI biomarker for assessing tissue microstructural integrity.
- Relapsing-remitting multiple sclerosis (RRMS) involves complex pathological changes affecting various brain tissues.
- Understanding these changes is crucial for effective disease management and monitoring.
Purpose of the Study:
- To investigate alterations in the T1w/T2w ratio across different brain tissue types and regions in RRMS patients.
- To examine the association between T1w/T2w ratio changes and cognitive function and disability in RRMS.
- To evaluate the T1w/T2w ratio as a potential neuroimaging biomarker for cognitive impairment in MS.
Main Methods:
- 72 RRMS patients and 70 healthy controls underwent MRI, neuropsychological testing, and EDSS assessment.
- T1w/T2w ratio mapping was performed, with mean ratio values extracted from various brain regions and tissue types.
- Statistical analyses included between-group comparisons and multiple linear regressions to assess associations with clinical outcomes, controlling for relevant covariates.
Main Results:
- RRMS patients exhibited significantly lower T1w/T2w ratios in white matter hyperintensity lesions, perilesional white matter, and specific deep gray matter and white matter tracts compared to controls.
- Conversely, higher T1w/T2w ratios were observed in other regions, including the putamen, pallidum, and internal capsule.
- Learning and memory performance positively correlated with T1w/T2w ratios in regions like the entorhinal cortex and caudate nucleus.
Conclusions:
- The T1w/T2w ratio displays spatially heterogeneous alterations in the brain of RRMS patients, reflecting complex underlying pathology.
- These regional variations in the T1w/T2w ratio are associated with cognitive deficits.
- The T1w/T2w ratio shows promise as a neuroimaging biomarker for detecting and understanding cognitive impairment in RRMS.

