Two molecular types of lesions via MRI

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Two molecular types of lesions via MRI

Post by frodo » Mon Sep 14, 2020 1:34 am

Characterization of multiple sclerosis lesions with distinct clinical correlates through quantitative diffusion MRI ... 8220302485


• Macroscopic and microscopic diffusion properties discriminate between MS lesion types.
• The number and volume of lesions with larger diffusion changes are associated with worse clinical outcomes.
• Diffusion MRI provides useful information of the pathological heterogeneity in plaques.


Diffusion magnetic resonance imaging can reveal quantitative information about the tissue changes in multiple sclerosis.

The recently developed multi-compartment spherical mean technique can map different microscopic properties based only on local diffusion signals, and it may provide specific information on the underlying microstructural modifications that arise in multiple sclerosis.

Given that the lesions in multiple sclerosis may reflect different degrees of damage, we hypothesized that quantitative diffusion maps may help characterize the severity of lesions “in vivo” and correlate these to an individual’s clinical profile.

We evaluated this in a cohort of 59 multiple sclerosis patients (62% female, mean age 44.7 years), for whom demographic and disease information was obtained, and who underwent a comprehensive physical and cognitive evaluation.

The magnetic resonance imaging protocol included conventional sequences to define focal lesions, and multi-shell diffusion imaging was used with b-values of 1000, 2000 and 3000 s/mm2 in 180 encoding directions. Quantitative diffusion properties on a macro- and micro-scale were used to discriminate distinct types of lesions through a k-means clustering algorithm, and the number and volume of those lesion types were correlated with parameters of the disease.

The combination of diffusion tensor imaging metrics (fractional anisotropy and radial diffusivity) and multi-compartment spherical mean technique values (microscopic fractional anisotropy and intra-neurite volume fraction) differentiated two type of lesions, with a prediction strength of 0.931.

The B-type lesions had larger diffusion changes compared to the A-type lesions, irrespective of their location (P <0.001). The number of A and B type lesions was similar, although in juxtacortical areas B-type lesions predominated (60%, P <0.001). Also, the percentage of B-type lesion volume was higher (60%, P <0.001), indicating that these lesions were larger. The number and volume of B-type lesions was related to the severity of disease evolution, clinical disability and cognitive decline (P =0.004, Bonferroni correction). Specifically, more and larger B-type lesions were correlated with a worse Multiple Sclerosis Severity Score, cerebellar function and cognitive performance.

Thus, by combining several microscopic and macroscopic diffusion properties, the severity of damage within focal lesions can be characterized, further contributing to our understanding of the mechanisms that drive disease evolution. Accordingly, the classification of lesion types has the potential to permit more specific and better-targeted treatment of patients with multiple sclerosis.

4 - Discussion

In this study, we demonstrate that MS lesions can be classified into two types based on the severity of the changes in terms of macroscopic DTI parameters and microscopic diffusion properties. We found that most patients had both types of lesions, although in nearly a quarter of the cohort there was a clear predominance towards a given lesion type. B-type lesions are thought to present more severe tissue damage, and the study demonstrates that their presence is related to a worse clinical evolution.

Specifically, a larger number of B-type lesions in the juxtacortical, cerebellar and deep WM areas was more strongly associated with disability, as was a larger volume of these lesions in periventricular regions. All in all, the results support the usefulness of diffusion MRI to obtain information in vivo on the heterogeneity of the pathological changes in MS plaques.

Our findings indicate that the combination of two diffusion-based models, DTI (FA and RD) and MC-SMT (μFA and ƒin), which can capture how water moves in the tissue over distinct timescales, enables two distinct types of MS lesions to be classified with high predictive value. Lesions with larger modifications in diffusion imaging properties are crucial to characterize the two MS lesion types (A-type lesions show higher FA, μFA and ƒin, and smaller RD values; while B-type lesions display lower FA, μFA and ƒin, and higher RD values on Supplementary Fig. 3). B-type lesions are thought to be associated with more severe demyelination and axonal damage (Yu et al., 2019). Therefore, the classification proposed would provide information regarding inflammatory destruction or the ability for neurorepair in a given patient, potentially representing a useful biomarker for phase II clinical trials.


The proportion of A and B type lesions was similar across the brain, except in juxtacortical areas where B-type lesions predominate. In periventricular regions, most of the lesion volume corresponds to B-type lesions, and such regional differences could reflect the nature of MS lesions in terms of their formation and evolution. This hypothesis is supported by the predominance of B-type lesions in SPMS patients (mean= 90%). Nevertheless, further longitudinal studies will be required to decipher the chronicity of those lesions and to assess whether they are related to slowly expanding plaques.

Previous studies showed that focal MS lesions, a hallmark of the disease, are weakly correlated with clinical disability (Barkhof, 2002) and disease severity (Mostert et al., 2010). However, our findings demonstrate that the number and volume of specific B-type lesions were strongly associated with a more severe disease evolution (correlation coefficients between 0.4 and 0.67), with a worse physical (mainly related to cerebellar functions) and cognitive disability. [...]

5. Conclusions

Microscopic features of the intracellular water domain (μFA and ƒin) and macroscopic DTI-derived metrics (FA, RD) together contribute to define the amount of damage within MS lesions. In turn, these features provide a specific pattern of lesion severity that helps understand the mechanisms underlying clinical disability and cognitive impairment in MS patients. Accordingly, the classification of lesion types has the potential to ensure MS patients receive more specific and better-targeted therapies.

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