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Updated: Apr 18, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
What drives MRI-measured cortical atrophy in multiple sclerosis?
V Popescu1, R Klaver2, P Voorn3
1Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, The Netherlands.
Background:
Cortical atrophy, assessed with magnetic resonance imaging (MRI), is an important outcome measure in multiple sclerosis (MS) studies. However, the underlying histopathology of cortical volume measures is unknown.
Objective:
We investigated the histopathological substrate of MRI-measured cortical volume in MS using combined post-mortem imaging and histopathology.
Methods:
MS brain donors underwent post-mortem whole-brain in-situ MRI imaging. After MRI, tissue blocks were systematically sampled from the superior and inferior frontal gyrus, anterior cingulate gyrus, inferior parietal lobule, and superior temporal gyrus. Histopathological markers included neuronal, axonal, synapse, astrocyte, dendrite, myelin, and oligodendrocyte densities. Matched cortical volumes from the aforementioned anatomical regions were measured on the MRI, and used as outcomes in a nested prediction model.
Results:
Forty-five tissue blocks were sampled from 11 MS brain donors. Mean age at death was 68±12 years, post-mortem interval 4±1 hours, and disease duration 35±15 years. MRI-measured regional cortical volumes varied depending on anatomical region. Neuronal density, neuronal size, and axonal density were significant predictors of GM volume.
Conclusions:
In patients with long-standing disease, neuronal and axonal pathology are the predominant pathological substrates of MRI-measured cortical volume in chronic MS.
Insights
In multiple sclerosis (MS), neuronal and axonal damage are key drivers of cortical volume loss seen on MRI, especially in long-standing disease. This study links brain imaging to underlying pathology.
Area of Science:
- Neuroscience
- Neuropathology
- Medical Imaging
Background:
- Cortical atrophy measured by MRI is a key outcome in multiple sclerosis (MS) research.
- The direct histopathological basis of these MRI-derived cortical volume measurements remains unclear.
Purpose of the Study:
- To determine the histopathological underpinnings of MRI-assessed cortical volume in multiple sclerosis.
- Utilizing combined post-mortem MRI and detailed histopathology to investigate cortical changes.
Main Methods:
- Post-mortem in-situ MRI was performed on brains from MS donors.
- Systematic tissue sampling from specific cortical regions (frontal, cingulate, parietal, temporal gyri).
- Histopathological analysis included neuronal, axonal, synaptic, glial, and myelin densities; these were correlated with MRI-measured regional volumes.
Main Results:
- MRI-measured cortical volumes exhibited regional variations across the sampled MS brains.
- Neuronal density, neuronal size, and axonal density were identified as significant predictors of gray matter (GM) volume.
- Data were derived from 11 MS brain donors, with 45 tissue blocks analyzed.
Conclusions:
- Neuronal and axonal pathology are the primary pathological substrates explaining MRI-measured cortical volume in chronic, long-standing multiple sclerosis.
- This research bridges the gap between in-vivo imaging and the microscopic tissue changes in MS.
