MS Lesion Analytics

Category: Biomarker

  • Evidence of progressive tissue loss in the core of chronic MS lesions: A longitudinal DTI study

    Evidence of progressive tissue loss in the core of chronic MS lesions: A longitudinal DTI study

    Progressive Tissue Loss in Chronic MS Lesions: Mechanisms of Brain Volume Loss

    This longitudinal study reveals how ongoing tissue damage within chronic MS lesions contributes to brain atrophy, offering new insights into disease progression even in treated patients.

    Key Findings:

    • Significant tissue loss occurs within chronic inactive MS lesions, with water diffusion increasing by 3.3% annually in lesion cores
    • Brain volume decreased by approximately 2% over the 5-year study period, showing continued atrophy despite treatment
    • Males showed nearly twice the rate of tissue damage compared to females, suggesting important gender differences in disease progression
    • Tissue damage within chronic lesions strongly correlated with overall brain atrophy, explaining 38% of brain volume changes

    Novel Technical Advances:

    • Used advanced diffusion tensor imaging to track microstructural changes over time
    • Developed methods to precisely analyze lesion cores separate from edges
    • Created techniques to account for brain atrophy when measuring lesion changes
    • Established ways to quantify progressive tissue damage in stable lesions

    Clinical Implications:

    • Explains why current MS treatments may not fully prevent disease progression
    • Suggests need for additional therapeutic approaches targeting chronic lesion damage
    • Highlights importance of considering gender differences in clinical trials
    • Demonstrates value of monitoring lesion changes to predict disease course

    Why It Matters:

    Understanding how chronic lesions continue to cause tissue damage even without new inflammation provides crucial insights into MS progression. The findings suggest that protecting demyelinated axons and promoting remyelination may be critical therapeutic goals, alongside current anti-inflammatory treatments.

    Link to manuscript

  • Expansion of chronic lesions is linked to disease progression in relapsing–remitting multiple sclerosis patients

    Expansion of chronic lesions is linked to disease progression in relapsing–remitting multiple sclerosis patients

    We investigated how chronic inflammatory lesions in multiple sclerosis evolve over time by studying their expansion patterns and relationship to disease progression in patients with relapsing-remitting MS over a 4-year period.

    Key Findings:

    • The expansion of chronic lesions, rather than formation of new lesions, accounts for most (67%) of total brain lesion volume increase in MS patients
    • Nearly half (46%) of chronic lesions showed significant expansion, while only 12% shrank over time
    • Lesion expansion strongly correlated with both brain atrophy and increased disability, suggesting it drives disease progression
    • Older patients showed higher rates of lesion expansion, potentially explaining accelerated disability in aging MS patients

    Novel Technical Advances:

    • Developed sophisticated imaging analysis methods to precisely track individual lesion changes over time
    • Created automated algorithms to distinguish between expanding chronic lesions and new lesion formation
    • Established quantitative measures to assess tissue damage within expanding lesions using diffusion imaging
    • Implemented rigorous controls for brain atrophy effects on lesion measurements

    Clinical Implications:

    • The dominant role of chronic lesion expansion in disease progression suggests new therapeutic targets are needed
    • Treatments focusing only on preventing new lesions may not adequately address ongoing tissue damage
    • Monitoring chronic lesion expansion could help identify patients at higher risk of progression
    • Age-related increases in lesion expansion indicate older patients may need different therapeutic approaches

    Why It Matters:

    This study fundamentally changes our understanding of how MS progresses by showing that the slow expansion of existing lesions, rather than formation of new ones, is the primary driver of accumulating disability. This challenges the traditional focus on preventing new lesion formation and suggests that therapies targeting chronic inflammation at lesion edges could help prevent disease progression. The findings explain why current treatments, while effective at reducing new lesions, may not fully prevent advancing disability, especially in older patients. This work provides crucial evidence for developing new therapeutic strategies aimed at the smoldering inflammation that causes lesion expansion.

    Link to manuscript

  • Expansion of chronic MS lesions is associated with an increase of radial diffusivity in periplaque white matter

    Expansion of chronic MS lesions is associated with an increase of radial diffusivity in periplaque white matter

    Demyelination as a Key Driver in Multiple Sclerosis Lesion Expansion

    Using our in-house single-streamline diffusion tensor imaging analysis, we investigated the relationship between chronic lesion expansion and tissue damage patterns in relapsing-remitting multiple sclerosis (RRMS), focusing on the role of demyelination and axonal injury.

    Key Findings:

    • Sequential Tissue Damage: Our analysis revealed that demyelination likely represents the initial step in chronic lesion expansion, preceding significant axonal damage
    • Differential Impact: We found that the rate of myelin damage in expanding lesions was twice that of axonal injury in surrounding tissue, suggesting demyelination as the primary early mechanism
    • Predictive Markers: Higher levels of myelin damage in periplaque white matter strongly predicted subsequent lesion expansion, while axonal damage markers showed weaker correlation
    • Expanding vs Stable Lesions: Expanding lesions showed significantly higher rates of ongoing demyelination compared to stable lesions, particularly in periplaque areas

    Clinical Implications:

    • These findings suggest that targeting early demyelination could be crucial for preventing lesion expansion
    • The identification of demyelination as an initial step provides a potential window for therapeutic intervention
    • Our results support the development of remyelinating therapies as a strategy to prevent associated neurodegeneration

    Why It Matters:

    Understanding the sequence of tissue damage in expanding MS lesions helps identify optimal timing for therapeutic interventions. By demonstrating that demyelination precedes significant axonal loss, this research suggests that early treatment targeting myelin protection or repair could help prevent the cascade of tissue damage that leads to progressive disability.

    Link to manuscript
  • Examining the Relative Contribution of Slow-Burning Inflammation and Chronic Demyelination to Axonal Damage in Chronic Multiple Sclerosis Lesions

    Examining the Relative Contribution of Slow-Burning Inflammation and Chronic Demyelination to Axonal Damage in Chronic Multiple Sclerosis Lesions

    Our study compared how two different mechanisms – slow-burning inflammation at lesion edges and chronic demyelination – contribute to tissue damage in multiple sclerosis lesions.

    Key Findings:

    • Expanding vs Stable Lesions: Of 361 lesions analyzed, 104 showed expansion while 257 remained stable, demonstrating distinct patterns of tissue damage
    • Inflammation Impact: Expanding lesions showed 5 times higher tissue damage rate compared to stable lesions, indicating slow-burning inflammation’s significant role
    • Demyelination Effects: Analysis of chronically demyelinated optic nerves revealed modest tissue damage similar to stable brain lesions, suggesting limited impact of demyelination alone

    Novel Technical Advances:

    • Developed method to normalize measurements of tissue damage across lesions
    • Created approach to exclude effects of new lesions on chronic lesion analysis
    • Used visual system to validate findings in a different part of the nervous system

    Clinical Implications:

    • Slow-burning inflammation appears more destructive than chronic demyelination
    • Treatments targeting inflammation at lesion edges may be more effective than those focusing on demyelination
    • Findings suggest need for early intervention to prevent lesion expansion

    Why It Matters:

    Understanding the relative impact of these two mechanisms helps guide treatment strategies for MS. Our findings suggest that controlling slow-burning inflammation at lesion edges should be a primary therapeutic target, potentially leading to more effective treatments that could slow disease progression.

    Link to manuscript

  • Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis

    Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis

    We developed an innovative method to analyze how multiple sclerosis lesions evolve over time, allowing us to separately measure and track nerve fiber loss and myelin damage using advanced brain imaging techniques. This new approach provides crucial insights into how MS causes progressive disability.

    Key Findings:

    • Our analysis revealed that nerve fiber loss and myelin damage contribute independently to MS lesion development, with different patterns of change over time
    • Nerve fiber loss shows a direct relationship with lesion severity – as lesions worsen, more nerve fibers are lost in a predictable way
    • Myelin damage has the greatest impact in early lesions when many nerve fibers are still intact, but becomes less prominent as nerve fiber loss increases
    • The rim area around lesions shows distinct patterns from the lesion core, making it potentially useful for monitoring treatment effects

    Novel Technical Advances:

    • Created a new single-fiber tracking method that can analyze MS lesions throughout the brain, not just in specific nerve pathways
    • Developed algorithms to separate and quantify nerve fiber loss from myelin damage within the same lesion
    • Established techniques to control for complex brain anatomy when measuring lesion changes
    • Implemented automated analysis approaches that enable consistent measurement across many patients

    Clinical Implications:

    • Provides a way to identify which lesions may respond best to remyelination therapies
    • Enables better monitoring of treatment effects by separately tracking nerve fiber and myelin changes
    • Suggests the lesion rim may be the optimal target for treatments aimed at protecting nerve fibers
    • Demonstrates why current MS treatments may have limited effects on progressive disability

    Why It Matters:

    This work fundamentally changes our understanding of how MS lesions evolve and cause disability. By showing that nerve fiber loss and myelin damage follow distinct patterns, we can better understand why some treatments work better than others and identify new therapeutic strategies. The ability to separately measure these two processes provides critical tools for developing and testing new treatments, particularly those aimed at protecting nerve fibers or promoting myelin repair. This advance may help explain why some patients progress faster than others and guide more personalized treatment approaches in MS.

    Link to manuscript
  • Quantifying Chronic Lesion Expansion in Multiple Sclerosis: Exploring Imaging Markers for Longitudinal Assessment

    Quantifying Chronic Lesion Expansion in Multiple Sclerosis: Exploring Imaging Markers for Longitudinal Assessment

    Our study investigated methods to accurately measure and predict chronic lesion expansion in multiple sclerosis (MS) using imaging data collected over 1-2 years, focusing on markers that don’t require longitudinal lesion segmentation.

    Key Findings:

    • Central Brain Atrophy (CBA): Measured over 2 years, CBA accurately predicts 4-year lesion expansion with 94% sensitivity and 85% specificity
    • Mean Diffusivity (MD): Changes in MD within chronic lesions strongly correlate with future expansion, providing 81% sensitivity and specificity
    • Progressive Volume/Severity Index: We developed this novel measure combining lesion volume changes and tissue damage severity to standardize assessment across patients

    Clinical Implications:

    • CBA offers a reliable early indicator of future lesion expansion without requiring complex lesion segmentation
    • The combination of multiple markers provides comprehensive assessment of disease progression
    • These findings enable shorter study periods for clinical trials evaluating new treatments

    Why It Matters:

    Early identification of patients likely to develop expanding lesions could inform treatment decisions and improve outcomes. Our markers provide practical tools for monitoring disease activity in clinical settings and trials.

    Link to manuscript
  • Mechanisms of Central Brain Atrophy in Multiple Sclerosis

    Mechanisms of Central Brain Atrophy in Multiple Sclerosis

    This study investigates how inflammation, including chronic and acute lesion activity, contributes to central brain atrophy (CBA) in patients with relapsing-remitting multiple sclerosis (RRMS).

    Key Findings:

    • Ventricular Enlargement: Over 4 years, patients experienced an average 12.6% increase in ventricular volume, driven largely by chronic lesion expansion.
    • Inflammatory Impact: Chronic lesion activity accounted for 69% of total lesion volume increase and emerged as the primary factor driving CBA.
    • Tissue Damage Severity: Incorporating measures of tissue damage significantly improved the understanding of how lesions contribute to atrophy, explaining 90% of CBA variability.

    Clinical Implications:

    • Chronic lesion expansion plays a pivotal role in neurodegeneration, underscoring its importance as a biomarker for MS progression.
    • Ventricular enlargement, a reliable and precise measure of CBA, offers a practical tool for monitoring MS progression and assessing treatment efficacy.

    Why It Matters:

    Understanding the mechanisms behind CBA enhances our ability to monitor MS progression, predict outcomes, and optimise therapeutic strategies.

    Link to manuscript

  • Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy

    Choroid plexus volume in multiple sclerosis predicts expansion of chronic lesions and brain atrophy

    Choroid Plexus Volume Predicts MS Lesion Evolution and Brain Atrophy

    Using our advanced imaging techniques, we investigated how the size of the choroid plexus – a key structure regulating immune cell entry into the brain – relates to the progression of multiple sclerosis. Our findings reveal an important early indicator of disease evolution.

    Key Findings:

    • Predictive Power: Enlarged choroid plexus volume strongly predicts future expansion of chronic MS lesions, particularly those near the brain’s ventricles, with 85% sensitivity and 76% specificity
    • Tissue Impact: Patients with enlarged choroid plexus showed accelerated tissue damage both within lesions and in surrounding brain regions, leading to faster brain atrophy
    • Early Marker: The choroid plexus appears enlarged early in the disease course and remains stable over time, suggesting it may be an early disease indicator rather than just a response to damage

    Clinical Implications:

    • The choroid plexus size could serve as a biomarker to identify patients at higher risk of aggressive disease progression
    • Patients with enlarged choroid plexus (above a specific threshold) have an 8-fold increased risk of lesion expansion
    • This metric could help stratify patients for clinical trials and guide treatment decisions, particularly for therapies targeting chronic inflammation

    Why It Matters:

    This research establishes the choroid plexus as a critical early player in MS progression rather than just a bystander. The strong predictive relationship between choroid plexus size and future tissue damage suggests this structure may actively drive chronic inflammation in MS. Understanding this connection opens new avenues for therapeutic intervention and disease monitoring, potentially enabling earlier identification of patients who may benefit from more aggressive treatment approaches.

    Link to manuscript

  • Evolution of Chronic Lesion Tissue in RRMS patients: An association with disease progression

    Evolution of Chronic Lesion Tissue in RRMS patients: An association with disease progression

    This study delves into the long-term progression of Chronic Lesion Tissue (CLT) in relapsing-remitting multiple sclerosis (RRMS) patients, examining its effects on clinical and radiological indicators of disease progression.

    Key Findings:

    • Consistent Growth: CLT increases at a steady annual rate of 7.75%, significantly impacting brain atrophy and disability.
    • Clinical Impact: Patients with higher CLT expansion exhibit faster central brain atrophy, particularly in deep grey matter, and worsening disability scores.

    Implications for Clinical Trials:

    • CLT expansion provides a promising biomarker for RRMS progression, offering a basis for designing smaller, targeted trials to evaluate therapies aimed at mitigating smouldering inflammation.
    • Calculations show that trials targeting CLT expansion require relatively small cohorts, making them feasible and efficient.

    Why It Matters:

    This research highlights the potential of monitoring CLT dynamics to better understand RRMS progression, tailor interventions, and refine clinical trial design.

    Link to manuscript