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ArticleEuropean radiology2026

Rule-based semi-automated method to segment black hole multiple sclerosis lesions on post-gadolinium 2D T1-weighted brain images.

Rozemarijn M Mattiesing, Fleur A Groeneveld, Iman Brouwer, Ronald A van Schijndel, Frederik Barkhof, Henk J M M Mutsaerts, Hugo Vrenken

Registry-linked trialAbstract readMulticenter Study
In one paragraph

Article in European radiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00813709 (Double-blind Extension of the Study 27025), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00813709 phase3completednot on this map

Double-blind Extension of the Study 27025 (REFLEX) to Obtain Long-term Follow-up Data in Patients With Clinically Definite MS and Patients With a First Demyelinating Event at High Risk of Converting to MS, Treated With Rebif® New Formulation (REFLEXION)

TypeinterventionalSponsorMerck KGaA, Darmstadt, GermanyRan2008 to 2013Enrolled402ConditionsMultiple Sclerosis, Clinically Isolated SyndromeArmsRNF, Placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Rozemarijn M MattiesingMS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands. r.mattiesing@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-5876-4260
Fleur A GroeneveldMS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
Iman BrouwerMS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
Ronald A van SchijndelMS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
Frederik BarkhofMS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
Henk J M M Mutsaerts *MS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
Hugo Vrenken *MS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.

Funding

Merck (CrossRef Funder ID: 10.13039/100009945) NA
6 · The paper itself

Abstract

objectivesTo develop a semi-automated method to segment "black hole" lesions on post-gadolinium 2D T1-weighted images (GdT1) in multiple sclerosis (MS) that follows radiological intensity rules and perform multi-center validation. MATERIALS AND

methodsMulti-center spin-echo GdT1 images and accompanying proton-density (PD)/T2-weighted images and manual T2 lesion masks of the REFLEXION study (NCT00813709) of suspected/early MS were used. Briefly, the proposed method segments cortical gray matter (GM) to derive a T1-weighted intensity threshold, which is applied inside co-registered T2 lesion masks to segment black hole lesion voxels. It was optimized on a training set (N = 40, 57.5% female, mean age 31.4 ± 8.7 (standard deviation) years), and 274 patients formed the test set (61.3% female, age 31.8 ± 8.4 years). Performance was quantified by the Dice similarity coefficient (DSC) and the intraclass correlation coefficient (ICC) for absolute agreement with manual segmentations. Lesion-wise sensitivity and specificity were calculated.

resultsOptimization resulted in: (1) GM selection as minimally 0.8 total WM plus GM partial volume, masked by MNI cortex; (2) normalized mutual information-driven linear co-registration of T2 to GdT1 images, interpolating T2 lesion masks using trilinear interpolation and 0.6 threshold; (3) mean intensity inside GM mask used as upper intensity threshold. The optimized method had acceptable spatial accuracy (DSC: 0.39 ± 0.26) and good volumetric accuracy (ICC: 0.84, 95% CI [0.72, 0.90]. Lesion-wise sensitivity was 0.91 ± 0.19, and lesion-wise specificity was 0.62 ± 0.22.

conclusionThe proposed method to semi-automatically segment black holes from post-gadolinium T1-weighted images shows acceptable performance. As a potential aid to radiologists, the method is not recommended to be used entirely without human intervention. KEY POINTS: Question T1-hypointense "black hole" lesions reflect disease severity in multiple sclerosis but are not routinely quantified due to a lack of reliable analysis methods. Findings A rule-based semi-automated method for GdT1 "black hole" lesion segmentation was developed and optimized, and then validated in a large unseen multi-center test set. Clinical relevance This method adds quantitative information about GdT1 "black hole" lesions to the radiological assessment of multiple sclerosis disease severity, when false positives are manually removed. This can enhance the characterization of individual patients and advance the understanding of the disease.

Indexed as

BrainGadoliniumImage Interpretation, Computer-AssistedMagnetic Resonance ImagingMultiple SclerosisAdultAlgorithmsContrast MediaFemaleHumansMaleReproducibility of ResultsSensitivity and SpecificityContrast MediaGadoliniumBrainComputer-assistedImage processingMagnetic resonance imagingMultiple sclerosis

Identifiers

PMID42069957
PMCPMC13451240

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.