Related Experiment Video
Updated: Jun 27, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
MRI as an outcome in multiple sclerosis clinical trials
M Daumer1, A Neuhaus, S Morrissey
1Sylvia Lawry Centre for Multiple Sclerosis Research, Munich, Germany.
Introduction:
T2-weighted and gadolinium enhanced T1-weighted MRI scans measure plaque burden and breakdown of the blood-brain barrier, respectively, in multiple sclerosis (MS) lesions. These have become widely used outcome measures for monitoring disease activity in clinical trials and clinical practice. However, their use as surrogates or biomarkers for disability and relapses, key clinical outcome measures, has remained incompletely validated.
Methods:
In a clinical trial database comprised of 31 relapsing-remitting and secondary progressive MS trial placebo groups, we assessed relationships between 1) T2 lesion load (TLL) change and disability change and 2) gadolinium enhancement of MS lesions and on-study relapses with univariate and multivariate analyses.
Results:
In relapsing-remitting MS, TLL change (n = 223) made no independent contribution to predicting change in disability from baseline to trials' end. Similarly, inclusion of gadolinium enhancing lesions (n = 170) into multivariate models did not independently contribute to the predictive value for on-trial relapses. In secondary progressive MS, a small effect of TLL was found for disability change (n = 355) but in multivariate analysis this accounted for less than 5% of the variance in end-of-trial disability. Results were replicated in independent datasets, more than doubling effective sample sizes.
Conclusions:
MRI measures widely used in trials of relapsing-remitting and progressive multiple sclerosis add little if anything independently to the clinically relevant relapse and disability outcomes. These results reemphasize the importance of validating potential surrogate markers against clinical measures and highlight the need for better MRI markers of disease activity and progression.
Insights
In multiple sclerosis (MS) clinical trials, MRI measures of plaque burden and blood-brain barrier breakdown do not reliably predict disability or relapses. Further validation and improved MRI markers are needed for accurate disease monitoring.
Area of Science:
- Neurology
- Radiology
- Biomarker Research
Background:
- T2-weighted and gadolinium-enhanced T1-weighted MRI scans are standard for assessing multiple sclerosis (MS) lesion activity.
- These MRI metrics are frequently used in clinical trials and practice to monitor disease progression.
- However, their validation as reliable surrogates for clinical outcomes like disability and relapses remains incomplete.
Purpose of the Study:
- To assess the predictive value of T2 lesion load and gadolinium-enhancing lesions for disability and relapse outcomes in MS.
- To determine if MRI measures independently contribute to predicting key clinical endpoints in relapsing-remitting and secondary progressive MS.
Main Methods:
- Analysis of a clinical trial database including placebo groups from 31 relapsing-remitting and secondary progressive MS trials.
- Univariate and multivariate analyses were used to examine relationships between T2 lesion load (TLL) change and disability change.
- The association between gadolinium-enhancing lesions and on-study relapses was also evaluated.
Main Results:
- In relapsing-remitting MS, T2 lesion load change did not independently predict disability change.
- Gadolinium-enhancing lesions did not independently contribute to predicting on-trial relapses in relapsing-remitting MS.
- In secondary progressive MS, T2 lesion load had a minor effect on disability, explaining less than 5% of the variance.
Conclusions:
- Current MRI measures of lesion load and enhancement offer limited independent predictive value for disability and relapse outcomes in MS clinical trials.
- These findings underscore the critical need for rigorous validation of surrogate markers against clinical endpoints.
- Development of more accurate MRI markers for MS disease activity and progression is essential.
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These technologies include computerized axial tomography (CAT or CT scans), positron-emission tomography (PET scans), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and Transcranial Magnetic Stimulation (TMS).