Abstract
Normal appearing white matter (NAWM) damage develops early in multiple sclerosis (MS) and continues in the absence of new lesions. The ratio of T1w and T2w (T1w/T2w ratio), a measure of white matter integrity, has previously shown reduced intensity values in MS NAWM. We evaluate the validity of a standardized T1w/T2w ratio (sT1w/T2w ratio) in MS and whether this method is sensitive in detecting MS-related differences in NAWM. T1w and T2w scans were acquired at 3 Tesla in 47 patients with relapsing-remitting MS and 47 matched controls (HC). T1w/T2w and sT1w/T2w ratios were then calculated. We compared between-group variability between T1w/T2w and sT1w/T2w ratio in HC and MS and assessed for group differences. We also evaluated the relationship between the T1w/T2w and sT1w/T2w ratios and clinically relevant variables. Compared to the classic T1w/T2w ratio, the between-subject variability in sT1w/T2w ratio showed a significant reduction in MS patients (p < 0.001) and HC (p < 0.001). However, only sT1w/T2w ratio values were reduced in patients compared to HC (p < 0.001). The sT1w/T2w ratio intensity values were significantly influenced by age, T2 lesion volume and group status (MS vs. HC) (adjusted R2 = 0.30, p < 0.001). We demonstrate the validity of the sT1w/T2w ratio in MS and that it is more sensitive to MS-related differences in NAWM compared to T1w/T2w ratio. The sT1w/T2w ratio shows promise as an easily-implemented measure of NAWM in MS using readily available scans and simple post-processing methods.
Highlights
Multiple sclerosis (MS) is an inflammatory and neurodegenerative CNS disease characterized by focal lesions with demyelination, axonal loss, and reactive gliosis in white matter (WM) and gray matter (GM) [1,2,3,4,5]
The coefficient of variation (CoV) of Normal appearing white matter (NAWM) intensity values was significantly reduced in sT1w/T2w compared to T1w/T2w in both patients and controls (Table 2)
We showed that [1] CoV of NAWM was reduced in the sT1w/T2w ratio compared to the T1w/T2w ratio, and [2] that NAWM group differences were more pronounced between healthy controls (HC) and multiple sclerosis (MS) using the sT1w/T2w ratio
Summary
Multiple sclerosis (MS) is an inflammatory and neurodegenerative CNS disease characterized by focal lesions with demyelination, axonal loss, and reactive gliosis in white matter (WM) and gray matter (GM) [1,2,3,4,5]. Tissue damage in the WM beyond lesions is frequently found in neuropathological examinations of MS, it is not detectable in routine clinical MRI scans. NAWM damage can be demonstrated using advanced MRI techniques such as diffusion tensor imaging [7,8,9] or other quantitative approaches [10]. Using these approaches, it has been shown that NAWM alone can discriminate MS patients from healthy subjects [10], indicating the high prevalence and sensitivity of NAWM in MS. Reduced T1w/T2w ratio intensity values have been found in the cortex and NAWM of MS patients compared to HC [15, 17]
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