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Serial magnetization transfer imaging to characterize the early evolution of new MS lesions
1NMR Research Unit, Institute of Neurology, London, UK.
Objective:
To explore the temporal relation of demyelination and blood-brain barrier breakdown during new lesion formation.
Background:
Conventional MRI appears sensitive for detecting changes due to MS, but may be limited by poor pathologic specificity. By indirectly assessing protons bound to rigid macromolecules, magnetization transfer (MT) imaging may provide information relating to tissue structure and, by inference, myelin integrity.
Methods:
Gadolinium contrast-enhanced MRI and MT imaging were performed at weekly intervals for 3 months in three patients with MS. For each enhancing lesion, the largest corresponding area of proton density hyperintensity seen during the study was outlined and magnetization transfer ratio (MTR) calculated at each time point from coregistered calculated MTR images. Lesions greater than 20 mm2, not affected by partial volume effects, and first enhancing after the baseline study were analyzed. Two-dimensional registration software allowed accurate evaluation of MTR in regions both before and after the initial appearance of MS lesions.
Results:
Mean lesion MTR decreased significantly during the first week of enhancement (29.6 percent units [pu] immediately pre-enhancement versus 28.2 pu at first documented stage of enhancement). No significant MTR reduction was noted before this.
Conclusion:
The lack of observable change in MTR before the first detectable gadolinium enhancement within MS lesions suggests that blood-brain barrier disruption is closely related to, but not preceded by, demyelination.
Insights
Blood-brain barrier breakdown in multiple sclerosis (MS) lesions closely follows demyelination. Magnetization transfer ratio (MTR) changes indicating myelin damage were not observed before gadolinium enhancement, suggesting BBB disruption is not preceded by demyelination.
Area of Science:
- Neuroimaging
- Multiple Sclerosis Pathophysiology
Background:
- Conventional MRI has limitations in pathological specificity for MS.
- Magnetization transfer (MT) imaging may offer insights into myelin integrity by assessing proton interactions.
Purpose of the Study:
- To investigate the temporal relationship between demyelination and blood-brain barrier (BBB) breakdown in new MS lesion formation.
Main Methods:
- Utilized Gadolinium-enhanced MRI and MT imaging over 3 months in three MS patients.
- Calculated Magnetization Transfer Ratio (MTR) in enhancing lesions before and after BBB breakdown.
- Analyzed lesions >20 mm² first enhancing after baseline, excluding partial volume effects.
Main Results:
- Mean MTR significantly decreased within the first week of lesion enhancement.
- No significant MTR reduction was observed prior to the initial detectable gadolinium enhancement.
Conclusions:
- BBB disruption in MS lesions is closely linked to demyelination.
- Demyelination does not appear to precede detectable BBB breakdown in new MS lesions.