Related Experiment Video
Updated: Jul 3, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Persistent T1 hypointensity as an MRI marker for treatment efficacy in multiple sclerosis
I J van den Elskamp1, J Lembcke, V Dattola
1Department of Radiology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. vandenelskamp@vume.nl
Background:
MRI is often used as primary outcome measure in phase II clinical trials in multiple sclerosis (MS). Since persistent T1 hypointense lesions are a surrogate parameter for axonal damage and demyelination, they may serve as a marker for monitoring the efficacy of neuroprotective drugs. At present, a power analysis using black hole (BH) evolution as primary outcome measure has not been performed.
Objective:
To assess the feasibility of using BH evolution on serial brain MR images as primary outcome measure in proof of concept studies in MS.
Methods:
MRI-data obtained from 169 active RRMS patients were analysed for BH evolution by determining the cumulative number of contrast enhancing lesions (CEL) evolving into a persistent black hole (PBH) after 3 months. With a parametric simulation procedure, based on a statistical distribution fitting the data, sample sizes were calculated.
Results:
21.2% of the total number of CELs observed during the study period evolved into a PBH. Ring enhancing lesions evolved most frequently into a PBH (59.4%), followed by lesions larger than 10 mm (57.4%) and periventricular CELs (30.6%). The simulation procedure, based on the statistical negative binomial (NB) model resulted in a sample sizes between 200 subjects and 30 subjects per arm, for treatment effects ranging from 50% to 90% reduction of the number of CELs evolving into a PBH, respectively.
Conclusion:
To perform a MRI monitored phase II clinical trial with a feasible sample size, using the evolution of CELs into PBHs as primary outcome parameter, a potent drug is required to obtain sufficient power.
Insights
Assessing black hole evolution in multiple sclerosis (MS) MRI scans is feasible for clinical trials. However, a potent drug is needed to achieve sufficient statistical power with a manageable sample size.
Area of Science:
- Neuroimaging
- Clinical Trials
- Neuroscience
Background:
- Magnetic Resonance Imaging (MRI) is crucial for Phase II multiple sclerosis (MS) trials.
- Persistent T1 hypointense lesions (black holes) indicate axonal damage and demyelination.
- Black hole evolution has not been previously analyzed for power in MS trials.
Purpose of the Study:
- To evaluate the feasibility of using black hole evolution on serial brain MR images as a primary outcome measure in MS proof-of-concept studies.
- To determine sample size requirements for such trials.
Main Methods:
- Analyzed MRI data from 169 active relapsing-remitting MS (RRMS) patients.
- Determined cumulative contrast-enhancing lesions (CELs) evolving into persistent black holes (PBHs) over 3 months.
- Calculated sample sizes using a parametric simulation procedure based on statistical distribution fitting.
Main Results:
- 21.2% of observed CELs evolved into PBHs.
- Ring-enhancing lesions (59.4%) and large lesions (>10mm, 57.4%) were most likely to become PBHs.
- Sample sizes ranged from 30 to 200 subjects per arm, depending on the desired treatment effect (50-90% reduction in PBH evolution).
Conclusions:
- Using CEL evolution into PBHs as a primary outcome in MRI-monitored Phase II MS trials is feasible.
- A potent drug is necessary to achieve adequate statistical power with a feasible sample size.
- This outcome measure can potentially monitor neuroprotective drug efficacy.
