What drives MRI-measured cortical atrophy in multiple sclerosis?

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.