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A serial study of new MS lesions and the white matter from which they arise
D E Goodkin1, W D Rooney, R Sloan
1Department of Neurology, University of California, San Francisco 94115, USA.
Objective:
To compare MS normal-appearing white matter (NAWM) where new gadolinium-enhancing (Gd+) lesions do and do not arise.
Methods:
A total of 22 relapsing-remitting MS patients and 11 healthy control subjects completed as many as 12 monthly brain MRI sessions. Quantitative measures of gadolinium enhancement (GDR), water proton density (PDN), water proton T2 relaxation time constants (T2), magnetization transfer ratio (MTR), and T1-weighted signal intensity (T1N) were followed serially in healthy control and MS NAWM.
Results:
A total of 129 new Gd+ lesions were identified in 11 patients. PDN, T2, MTR, and T1N were diffusely abnormal in MS NAWM. NAWM regions in which new Gd+ lesions arose have increased GDR, PDN, and T2, and reduced MTR and T1N compared with contralateral homologous NAWM regions in which no new Gd+ lesions arose. Differences between these NAWM regions preceded lesion appearance for at least several months. After lesions became visible, GDR returned to baseline within 2 months, and PDN and MTR had larger residual abnormalities than T2 or T1N.
Conclusions:
Quantitative MRI measures are diffusely abnormal in MS NAWM. These measures are, on average, more abnormal in NAWM regions in which new Gd+ lesions arise. After the appearance of Gd+ lesions, measures of PDN and MTR may provide more appealing markers of relatively irreversible tissue damage than measures of T2 and T1N.
Insights
In multiple sclerosis (MS), normal-appearing white matter (NAWM) shows diffuse abnormalities. Regions developing new gadolinium-enhancing (Gd+) lesions exhibit more severe changes preceding lesion appearance.
Area of Science:
- Neuroimaging
- Neurology
- Biomedical Engineering
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system.
- Normal-appearing white matter (NAWM) in MS patients exhibits subtle, diffuse abnormalities.
- Understanding the evolution of NAWM is crucial for predicting lesion development.
Purpose of the Study:
- To compare MS normal-appearing white matter (NAWM) where new gadolinium-enhancing (Gd+) lesions do and do not arise.
- To identify early MRI markers predictive of future lesion formation in MS.
- To characterize the longitudinal changes in NAWM properties.
Main Methods:
- Serial monthly brain MRI scans were performed on 22 relapsing-remitting MS patients and 11 healthy controls.
- Quantitative MRI measures including gadolinium enhancement (GDR), proton density (PDN), T2 relaxation time (T2), magnetization transfer ratio (MTR), and T1-weighted signal intensity (T1N) were assessed.
- NAWM regions were analyzed for differences based on the subsequent appearance of Gd+ lesions.
Main Results:
- Diffuse abnormalities in PDN, T2, MTR, and T1N were observed in MS NAWM.
- NAWM regions that later developed Gd+ lesions showed increased GDR, PDN, T2, and decreased MTR and T1N compared to unaffected contralateral NAWM.
- These quantitative MRI differences preceded the visible appearance of Gd+ lesions by several months.
Conclusions:
- Quantitative MRI measures reveal widespread abnormalities in MS NAWM.
- These abnormalities are more pronounced in NAWM regions that subsequently develop Gd+ lesions.
- PDN and MTR may serve as more robust markers of irreversible tissue damage post-lesion formation compared to T2 and T1N.