In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis

Objective

To quantify alterations in soma and neurite density imaging measures within and surrounding cortical lesions in people with multiple sclerosis using in vivo high-gradient diffusion MRI.

Methods

In this cross-sectional study, 41 people with multiple sclerosis and 34 age- and sex-matched healthy controls underwent 3 T high-gradient diffusion MRI. Cortical lesions were segmented on artificial intelligence-enabled double inversion recovery images. “Inner” and “outer” perilesional layers were segmented as two expanding shells of 2 mm surrounding a cortical lesion. Intracellular, intra-neurite, and extracellular signal fractions and apparent soma radius were estimated in (peri)lesional and normal-appearing cortex.

Results

Cortical lesions were present in all people with multiple sclerosis with a median count of 8 [IQR 5–18] and total volume of 0.16 [0.09–0.46 mL]. People with multiple sclerosis (mean 0.27 ± 0.03) showed lower normalized cortical volumes compared to healthy controls (0.30 ± 0.02). Compared to healthy controls (mean 0.58 ± 0.028), normal-appearing cortex in multiple sclerosis (0.57 ± 0.034) showed lower intra-cellular signal fraction. Cortical lesions (0.49 ± 0.089) exhibited lower intra-cellular signal fractions compared to perilesional (“inner”: 0.55 ± 0.049, “outer”: 0.55 ± 0.039) and normal-appearing cortex, demonstrating a gradation of change. The soma radius varied significantly across cortices, becoming smaller when moving outward from cortical lesions (cortical lesions: 10.38 ± 0.209 μm, “inner” layer: 10.19 ± 0.140 μm, “outer” layer: 10.07 ± 0.149 μm, normal-appearing cortex: 9.99 ± 0.127 μm).

Interpretation

Cortical cell body loss in multiple sclerosis is most pronounced in cortical lesions and also present in normal-appearing cortex. Gradients of diffusion microstructural alterations moving outward from cortical lesions toward normal-appearing cortex highlight the potential of high-gradient diffusion MRI to identify both focal and diffuse cortical pathology.