The relationship between lesion and normal appearing brain tissue abnormalities in early relapsing remitting multiple sclerosis
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Updated: Oct 1, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Colette M Griffin1, Declan T Chard, Geoff J M Parker
1NMR Research Unit, Institute of Neurology, London, UK.
Background:
In multiple sclerosis (MS), pathological changes have been found both in macroscopic lesions and normal appearing tissue. Magnetisation transfer ratio (MTR) and T1 relaxation time are abnormal in normal appearing tissues in established MS. This study used these MR techniques in early MS to study normal appearing tissues and lesions. The purpose was to determine whether abnormalities are already detectable in normal appearing tissues in early MS, and if so how they correlate with lesion characteristics.
Methods:
Twenty two patients with early relapsing remitting (RR) MS (median disease duration 2 years, range 7 months-3 years) and 11 age-matched controls were studied. MTR and T1 relaxation times were measured in 9 regions of normal appearing white matter (NAWM) and 7 of normal appearing grey matter (NAGM). Gadolinium enhancing, T1-hypointense and T2 lesion loads were measured in all patients.
Results:
When all regions were combined, there was a significant difference between patient and control NAWM for both T1 and MTR; T1 was abnormal in 6/9 and MTR in 3/9 NAWM regions. Global assessment of NAGM revealed a significant difference between patients and controls for Ti but not for MTR; T1 was significantly abnormal only in frontal NAGM. There was no significant correlation between NAWM T1 or MTR and any of the lesion load measurements.
Conclusions:
This study reveals quantitative MR abnormalities in both NAWM and NAGM in early RR MS, with more extensive changes in the former. The lack of correlation between NAWM and lesion abnormalities suggests that they have developed by at least partly independent mechanisms. T1 may be more sensitive than MTR in detecting subtle pathological changes in NAWM and NAGM.
Insights
Early multiple sclerosis (MS) shows magnetic resonance imaging (MRI) abnormalities in normal-appearing white and grey matter. These changes in T1 relaxation time and Magnetisation Transfer Ratio (MTR) appear independent of lesion load.
Area of Science:
- Neuroimaging
- Neurology
- Biomedical Engineering
Background:
- Pathological changes in multiple sclerosis (MS) affect both visible lesions and normal-appearing brain tissue.
- Established MS exhibits abnormal Magnetisation Transfer Ratio (MTR) and T1 relaxation times in normal-appearing tissues.
Purpose of the Study:
- To investigate if MRI abnormalities are detectable in normal-appearing tissues in early MS.
- To correlate these early abnormalities with lesion characteristics.
Main Methods:
- Studied 22 early relapsing-remitting MS patients and 11 age-matched controls.
- Measured MTR and T1 relaxation times in normal-appearing white matter (NAWM) and normal-appearing grey matter (NAGM).
- Quantified gadolinium-enhancing, T1-hypointense, and T2 lesion loads.
Main Results:
- Significant differences in T1 and MTR between MS patients and controls in NAWM.
- T1 abnormalities were found in 6/9 NAWM regions, and MTR in 3/9.
- T1, but not MTR, was significantly abnormal in frontal NAGM.
- No significant correlation was found between NAWM T1/MTR and lesion load.
Conclusions:
- Early relapsing-remitting MS demonstrates quantitative MRI abnormalities in both NAWM and NAGM.
- Abnormalities in NAWM are more extensive than in NAGM.
- The lack of correlation suggests independent development of tissue abnormalities and lesions.
- T1 relaxation time may be more sensitive than MTR for detecting subtle changes in early MS.
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