Clinical trials in multiple sclerosis (MS) have long been challenged by high rates of patient misdiagnosis and heterogeneous study populations. However, the landscape is changing. The MS diagnostic journey has hit a pivotal turning point in the path to more precise patient recruitment and stronger regulatory submissions. For decades, the McDonald criteria have been the cornerstone of MS diagnosis. Whispers of their next iteration became a definitive announcement at ECTRIMS 2024. Now, one year later, in the wake of the 2025 edition of ECTRIMS in Barcelona, the highly anticipated new criteria are finally here.
The 2024 McDonald criteria represent a monumental shift in MS diagnosis, introducing advanced MRI biomarkers for the first time. While previous criteria partly relied on MRI - specifically, white matter hyperintensities detected by conventional sequences - the non-specificity of these imaging markers were a contributing factor in the high rates of MS misdiagnosis. The incorporation of two new MRI biomarkers are set to bring an unprecedented level of diagnostic specificity that moves the field from guesswork towards biological precision.
The Next Iteration of the McDonald Criteria for MS
Specificity in Numbers
Central Vein Sign (CVS): A Window into MS Pathology
The in vivo visualization of the hypothesized foundational - and highly pathognomonic - pathological event in MS: the infiltration of inflammatory cells from a small central vein into the adjacent white matter. The CVS appears as a small hypointense line within the hyperintense lesion when imaged using susceptibility-sensitive MRI sequences.
Meta-analyses highlight the high sensitivity (91%) and specificity (96%) of the CVS and therefore its utility in distinguishing MS from mimicking diseases. Studies show that it is capable of achieving similar diagnostic performance to CSF markers.
Paramagnetic Rim Lesions (PRL): An Emerging Biomarker
An MRI marker representative of chronic, smoldering inflammatory activity and generally ongoing demyelination at the lesion edge. An iron-rich infiltrate is visualized as a ‘paramagnetic rim’ coincident with the white matter lesion on susceptibility-sensitive MRI.
PRLs associate well with greater disease severity and are thought to be a possible driver of disease progression. A recent study places their specificity for discriminating MS from other inflammatory and non-inflammatory neurological diseases as high as 98%.
What The New Reality of MS Imaging Means For You
For Academic and Clinical Researchers - the high-speed translation of CVS and PRLs from research to clinical practice are an encouraging and powerful example of biomarker discovery. Through collaboration with neuroradiologists, researchers must continue to integrate these markers into their work to homogenize study cohorts and better understand disease processes, ultimately fostering further discovery.
For Sponsors and CROs - more precise biomarkers offer direct improvements in patient recruitment and stratification, elevating the chances of trial success. PRLs in particular hold the promise of high value as a therapeutic endpoint. Early adoption of these biomarkers will be crucial to not only ensure regulatory efficiency but also to position your organization as a leader in the field.
QMENTA Are Ready to Help You Get Started, Fast
QMENTA isn’t just another biomarker company selling a new tool - we actually helped develop the science behind them.
QMENTA engineered the foundation that powered CAVS-MS, the first-of-its-kind, landmark multi-site trial that validated CVS biomarkers for real-world MS diagnosis. When leading researchers Dr. Daniel Ontaneda (Cleveland Clinic) and Dr. Pascal Sati (Cedars-Sinai) needed to prove these biomarkers could work across multiple institutions and diverse patient populations, they chose QMENTA.
Our platform solved the operational problems that derail most multi-site imaging studies: seamless data integration across institutions, automated quality control that catches issues before they impact timelines, and regulatory-ready documentation from the start. The result? The first successful validation of CVS biomarkers that regulatory bodies now recognize - and the only platform with proven experience deploying them at scale.
QMENTA’s data management solution ensured the success of the CAVS-MS study through:
- Centralized Data Management & Quality Control: A unified data repository with built-in quality control metrics, automated protocol adherence rules, and comprehensive audit trails addressing the chaos of managing imaging data across multiple sites while ensuring regulatory compliance and data integrity for trial submissions.
- Custom CVS Detection Workflow: Our team worked with leading academics to build an image analysis pipeline from the ground up - suitable for the specialized, non-standard MRI sequences required. Through the success of the study, this pipeline was validated by KOLs and is now available in the QMENTA Platform.
- AI-Powered Lesion Segmentation: Our proprietary deep learning-based algorithm automatically identifies and maps white matter lesions, reducing the time radiologists spend on manual segmentation while maintaining accuracy. The output can then be reviewed and refined manually, combining efficiency with expert oversight.
- Electronic Data Capture & Export: All findings, including lesion counts, volume, and separate assessments for dissemination in space/time (DIS/DIT), were automatically captured in standardized formats and exported as trial-ready metadata.
- Regulatory-Ready Documentation & Validation: Pre-validated workflows with complete validation packages, immutable audit trails, and standardized documentation that meet regulatory requirements from day one - eliminating the tedious processes that delay regulatory submissions when using legacy imaging approaches.
Read about our end-to-end CVS solution in more detail here.
QMENTA Are The Expert’s Choice
Thanks to this collaboration, QMENTA’s infrastructure is already poised to drive the widespread adoption of these biomarkers fast. We understand the challenges and solutions, because we’ve already overcome them. This deep experience is coupled with our broader mission to provide:
- Centralized data management for multi-center studies, with decentralized central reading capabilities.
- Web browser access with the possibility of a subscription-based model.
- Results transparency - we produce more than just a PDF report, meaning your results will never be a black box.
- Flexibility & adaptability for testing and validating novel and proof-of-concept methodologies, such as ‘the next CVS or PRL’.
- Ease of integration with other imaging endpoints, such as volumetric measures.
- Unrivalled support from our team of experts.
The Time to Leverage Advanced MRI in MS is Now
The new 2024 McDonald criteria herald a new era in MS diagnosis and clinical trials, one defined by biological precision and technological enablement. By embracing these advancements, the clinical and research communities can work to reduce misdiagnosis and improve outcomes for people living with MS.
As the field shifts from discovery to implementation, the question no longer remains whether advanced markers can improve specificity, but how to integrate them consistently across centers and trials. QMENTA can provide the validated infrastructure to make that happen for your study right now.
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