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Updated: Jul 6, 2025
Magnetic Resonance Elastography Methodology for the Evaluation of Tissue Engineered Construct Growth
Published on: February 9, 2012
Cortical matrix remodeling as a hallmark of relapsing-remitting neuroinflammation in MR elastography and quantitative
Rafaela V Silva1,2,3,4, Anna S Morr5, Helge Herthum6
1Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.
Abstract:
Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE). However, it needs to be established if changes of the spatiotemporal patterns of brain tissue mechanics constitute a marker of neuroinflammation. Here, we use advanced multifrequency MRE with tomoelastography postprocessing to investigate longitudinal and regional inflammation-induced tissue changes in EAE and in a small group of MS patients. Surprisingly, we found reversible softening in synchrony with the EAE disease course predominantly in the cortex of the mouse brain. This cortical softening was associated neither with a shift of tissue water compartments as quantified by T2-mapping and diffusion-weighted MRI, nor with leukocyte infiltration as seen by histopathology. Instead, cortical softening correlated with transient structural remodeling of perineuronal nets (PNNs), which involved abnormal chondroitin sulfate expression and microgliosis. These mechanisms also appear to be critical in humans with MS, where tomoelastography for the first time demonstrated marked cortical softening. Taken together, our study shows that neuroinflammation (i) critically affects the integrity of PNNs in cortical brain tissue, in a reversible process that correlates with disease disability in EAE, (ii) reduces the mechanical integrity of brain tissue rather than leading to water accumulation, and (iii) shows similar spatial patterns in humans and mice. These results raise the prospect of leveraging MRE and quantitative MRI for MS staging and monitoring treatment in affected patients.
Insights
Neuroinflammation in multiple sclerosis (MS) causes reversible brain softening, particularly in the cortex, linked to perineuronal net remodeling, not water changes. This finding may aid MS monitoring.
Area of Science:
- Neuroscience
- Biophysics
- Medical Imaging
Background:
- Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting brain white and gray matter, with gray matter pathology significantly contributing to patient disability.
- Conventional magnetic resonance imaging (MRI) struggles to accurately detect gray matter pathology and correlate it with clinical symptoms in MS.
- Previous studies using magnetic resonance elastography (MRE) indicated global brain softening in MS and experimental autoimmune encephalomyelitis (EAE), but the link between spatiotemporal mechanical changes and neuroinflammation needed clarification.
Purpose of the Study:
- To investigate longitudinal and regional inflammation-induced tissue changes in EAE and MS using advanced multifrequency MRE with tomoelastography.
- To determine if changes in brain tissue mechanics, specifically cortical softening, serve as a marker for neuroinflammation.
- To explore the underlying mechanisms of cortical softening, including tissue water content, leukocyte infiltration, and perineuronal net (PNN) integrity.
Main Methods:
- Advanced multifrequency MRE with tomoelastography postprocessing was employed to analyze tissue mechanics in EAE mice and a small cohort of MS patients.
- T2-mapping and diffusion-weighted MRI were used to quantify tissue water compartments.
- Histopathology was performed to assess leukocyte infiltration, and PNNs were examined for structural remodeling and chondroitin sulfate expression.
Main Results:
- Reversible cortical softening was observed in synchrony with the EAE disease course, predominantly in the mouse cortex.
- Cortical softening was not associated with changes in tissue water compartments or leukocyte infiltration.
- Softening correlated with transient structural remodeling of PNNs, abnormal chondroitin sulfate expression, and microgliosis, mechanisms also implicated in MS patients showing marked cortical softening via tomoelastography.
Conclusions:
- Neuroinflammation critically affects PNN integrity in cortical brain tissue, leading to reversible softening that correlates with disease disability in EAE.
- Inflammation reduces brain tissue's mechanical integrity through mechanisms other than water accumulation.
- The observed spatial patterns of inflammation-induced cortical softening are similar in humans with MS and in the EAE model, suggesting MRE's potential for MS staging and treatment monitoring.
