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.