Journal Article

A novel imaging marker of cortical “cellularity” in multiple sclerosis patients

Weigel, Matthias, Chen, Xinjie, Kuhle, Jens, Ocampo-Pineda, Mario, Lu, Po-Jui, Stadelmann, Christine, Kappos, Ludwig, Magon, Stefano, Palombo, Marco, Melie-Garcia, Lester, Cagol, Alessandro, Bahn, Erik, Barakovic, Muhamed, Schaedelin, Sabine, Granziera, Cristina, Galbusera, Riccardo

2024

Overview

Pathological data showed focal inflammation and regions of diffuse neuronal loss in the cortex of people with multiple sclerosis (MS). In this work, we applied a novel model (“soma and neurite density imaging (SANDI)”) to multishell diffusion-weighted MRI data acquired in healthy subjects and people with multiple sclerosis (pwMS), in order to investigate inflammation and degeneration-related changes in the cortical tissue of pwMS. We aimed to (i) establish whether SANDI is applicable in vivo clinical data; (ii) investigate inflammatory and degenerative changes using SANDI soma fraction ( f soma )—a marker of cellularity—in both cortical lesions and in the normal-appearing-cortex and (iii) correlate SANDI f soma with clinical and biological measures in pwMS. We applied a simplified version of SANDI to a clinical scanners. We then provided evidence that pwMS exhibited an overall decrease in cortical SANDI f soma compared to healthy subjects, suggesting global degenerative processes compatible with neuronal loss. On the other hand, we have found that progressive pwMS showed a higher SANDI f soma in the outer part of the cortex compared to relapsing–remitting pwMS, possibly supporting current pathological knowledge of increased innate inflammatory cells in these regions. A similar finding was obtained in subpial lesions in relapsing–remitting patients, reflecting existing pathological data in these lesion types. A significant correlation was found between SANDI f soma and serum neurofilament light chain—a biomarker of inflammatory axonal damage—suggesting a relationship between SANDI soma fraction and inflammatory processes in pwMS again. Overall, our data show that SANDI f soma is a promising biomarker to monitor changes in cellularity compatible with neurodegeneration and neuroinflammation in the cortex of MS patients.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114/116/2392 / 692/308/575 / 692/617/375/1666 / Adult / Biomarkers / Cerebral Cortex - diagnostic imaging / Cerebral Cortex - pathology / Cortex / Diffusion Magnetic Resonance Imaging - methods / Female / Humanities and Social Sciences / Humans / Inflammation / Inflammation - diagnostic imaging / Inflammation - pathology / Lesions / Male / Middle Aged / multidisciplinary / Multiple sclerosis / Multiple Sclerosis - diagnostic imaging / Multiple Sclerosis - pathology / Neurites - pathology / Neurodegeneration / Neuroimaging / Science / Science (multidisciplinary)