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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Soma and neurite density abnormalities of paramagnetic rim lesions and core-sign lesions in multiple sclerosis
Paolo Preziosa1,2,3, Elisabetta Pagani4, Alessandro Meani4
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. preziosa.paolo@hsr.it.
Background:
In multiple sclerosis (MS), susceptibility-weighted imaging (SWI) may reveal white matter lesions (WML) with a paramagnetic rim ("paramagnetic rim lesions" [PRLs]) or diffuse hypointensity ("core-sign lesions"), reflecting different stages of WML evolution.
Objective:
Using the soma and neurite density imaging (SANDI) model on diffusion-weighted magnetic resonance imaging (MRI), we characterized microstructural abnormalities of MS PRLs and core-sign lesions and their clinical relevance.
Methods:
Forty MS patients and 20 healthy controls (HC) underwent a 3 T brain MRI. Using SANDI, the fractions of neurite (fneurite) and soma (fsoma) and size of soma (rsoma) were quantified in PRLs (including their core and rim separately), and core-sign lesions identified on SWI-phase.
Results:
Among 1811 WMLs, 122 (6.7%) core-sign lesions and 97 (5.4%) PRLs were identified. Compared to HC and MS normal-appearing white matter, all MS WML showed significantly lower fneurite and fsoma and higher rsoma (FDR-p < 0.001). Compared to SWI-isointense WML, core-sign lesions showed a significantly higher fneurite, and lower fsoma and rsoma (FDR-p ≤ 0.005). Compared to SWI-isointense WML and core-sign lesions, PRLs showed a significantly lower fneurite, higher fsoma, and higher rsoma (FDR-p ≤ 0.001). The PRL-core showed significantly lower fneurite, and higher rsoma than PRL-rim (FDR-p < 0.001). Lower PRL fneurite (β ≤ -0.006, FDR-p ≤ 0.015) and higher rsoma (β ≥ 0.032, FDR-p ≤ 0.024) were significantly associated with a longer disease duration and more severe disability.
Conclusions:
In PRLs, the significant and clinically relevant neurite loss and increased soma fraction and size possibly reflect increased astrogliosis and activated microglia. Core-sign lesions exhibit milder axonal loss, microglia density and astrogliosis, supporting their less destructive nature.
Insights
Multiple sclerosis white matter lesions show distinct microstructural changes. Paramagnetic rim lesions indicate more severe neurite loss and astrogliosis than core-sign lesions, correlating with disease progression.
Area of Science:
- Neuroimaging
- Neuroinflammation
- Multiple Sclerosis Pathophysiology
Background:
- Susceptibility-weighted imaging (SWI) identifies white matter lesions (WML) in multiple sclerosis (MS) as paramagnetic rim lesions (PRLs) or core-sign lesions, indicating different stages of WML evolution.
- These SWI findings suggest distinct underlying pathological processes within MS lesions.
Purpose of the Study:
- To characterize the microstructural abnormalities in MS PRLs and core-sign lesions using the soma and neurite density imaging (SANDI) model.
- To investigate the clinical relevance of these microstructural differences in MS patients.
Main Methods:
- Diffusion-weighted magnetic resonance imaging (MRI) was performed on 40 MS patients and 20 healthy controls (HC).
- The SANDI model quantified neurite fraction (fneurite), soma fraction (fsoma), and soma size (rsoma) in WMLs, including PRL cores and rims, and core-sign lesions.
- Statistical analyses compared microstructural parameters between lesion types and with normal-appearing white matter, and correlated them with clinical data.
Main Results:
- All MS WMLs exhibited reduced fneurite, fsoma, and increased rsoma compared to HC.
- Core-sign lesions showed higher fneurite and lower fsoma and rsoma than SWI-isointense WMLs.
- PRLs demonstrated significantly lower fneurite, higher fsoma, and higher rsoma than both SWI-isointense WMLs and core-sign lesions.
- PRL cores had lower fneurite and higher rsoma than PRL rims.
- Lower PRL fneurite and higher rsoma correlated with longer disease duration and greater disability.
Conclusions:
- PRLs are characterized by significant neurite loss and increased soma fraction/size, suggesting astrogliosis and activated microglia.
- Core-sign lesions display milder axonal loss and glial activation, indicating a less destructive process.
- SANDI model provides insights into the microstructural heterogeneity and clinical impact of different MS WML types.
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