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Published on: April 14, 2014
Imaging outcomes for neuroprotection and repair in multiple sclerosis trials
Frederik Barkhof1, Peter A Calabresi, David H Miller
1Department of Radiology and Amsterdam MS Center, VU University Medical Center, Amsterdam, The Netherlands. f.barkhof@vumc.nl
Abstract:
Multiple sclerosis (MS) is commonly regarded as an inflammatory disease, but it also has a neurodegenerative component, which represents an additional target for treatment. The use of MRI to evaluate the inflammatory disease component in 'proof-of concept' clinical trials is well established, but no systematic assessment of imaging outcomes to evaluate neuroprotection or repair in MS has been performed. In this Review, we examine the potential of traditional and novel imaging parameters to serve as primary outcomes in phase II clinical trials of neuroprotective and reparative strategies in MS. We present the conclusions of an international meeting of imaging, clinical and statistical experts, as well as a review of relevant literature. The available imaging techniques are appraised in five categories of performance: pathological specificity, reproducibility, sensitivity to change, clinical relevance, and response to treatment. At present, the three most promising primary outcomes in phase II trials of neuroprotective and/or reparative strategies in MS are: changes in whole-brain volume to gauge general cerebral atrophy; T1 hypointensity and magnetization transfer ratio to monitor the evolution of lesion damage; and optical coherence tomography findings to evaluate the anterior visual pathway. Power calculations show that these outcome measures can be applied with attainable sample sizes.
Insights
Multiple sclerosis (MS) research is exploring neuroprotection and repair beyond inflammation. This review identifies key imaging outcomes like brain volume and lesion changes for clinical trials, offering new treatment targets.
Area of Science:
- Neurology
- Radiology
- Clinical Trials
Background:
- Multiple sclerosis (MS) is characterized by both inflammation and neurodegeneration.
- While MRI effectively tracks inflammation in MS trials, validated imaging outcomes for neuroprotection and repair are lacking.
- Neurodegenerative aspects of MS present a crucial target for novel therapeutic strategies.
Purpose of the Study:
- To systematically assess imaging parameters for evaluating neuroprotection and repair in MS clinical trials.
- To identify optimal primary outcomes for phase II trials investigating neuroprotective and reparative therapies in MS.
- To synthesize expert consensus and literature review on the utility of imaging in MS neuroprotection studies.
Main Methods:
- Review of relevant scientific literature on MS imaging outcomes.
- Appraisal of imaging techniques based on pathological specificity, reproducibility, sensitivity to change, clinical relevance, and treatment response.
- Analysis of conclusions from an international expert meeting comprising imaging, clinical, and statistical specialists.
Main Results:
- Whole-brain volume changes are promising for assessing general cerebral atrophy.
- T1 hypointensity and magnetization transfer ratio effectively monitor lesion evolution and damage.
- Optical coherence tomography provides valuable insights into the anterior visual pathway in MS.
Conclusions:
- Whole-brain volume, T1 hypointensity, magnetization transfer ratio, and optical coherence tomography are identified as key imaging outcomes for MS neuroprotection trials.
- These selected imaging measures demonstrate feasibility with attainable sample sizes for phase II clinical trials.
- The findings provide a framework for advancing the evaluation of neuroprotective and reparative strategies in multiple sclerosis.
