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

Abstract 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‐ma...

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Main Authors: Eva A. Krijnen, Hansol Lee, Samantha Noteboom, Florence L. Chiang, Martijn D. Steenwijk, Menno M. Schoonheim, Eric C. Klawiter, Susie Y. Huang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Annals of Clinical and Translational Neurology
Online Access:https://doi.org/10.1002/acn3.52237
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author Eva A. Krijnen
Hansol Lee
Samantha Noteboom
Florence L. Chiang
Martijn D. Steenwijk
Menno M. Schoonheim
Eric C. Klawiter
Susie Y. Huang
author_facet Eva A. Krijnen
Hansol Lee
Samantha Noteboom
Florence L. Chiang
Martijn D. Steenwijk
Menno M. Schoonheim
Eric C. Klawiter
Susie Y. Huang
author_sort Eva A. Krijnen
collection DOAJ
description Abstract 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.
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spelling doaj-art-30c0f9faf7344828a17b1bccf4b924b82025-01-21T05:41:42ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-01-0112141610.1002/acn3.52237In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosisEva A. Krijnen0Hansol Lee1Samantha Noteboom2Florence L. Chiang3Martijn D. Steenwijk4Menno M. Schoonheim5Eric C. Klawiter6Susie Y. Huang7Department of Neurology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114 USAAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts 02129 USAMS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience Amsterdam UMC location VUmc 1007 MB Amsterdam The NetherlandsAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts 02129 USAMS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience Amsterdam UMC location VUmc 1007 MB Amsterdam The NetherlandsMS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience Amsterdam UMC location VUmc 1007 MB Amsterdam The NetherlandsDepartment of Neurology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114 USAAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital Harvard Medical School Charlestown Massachusetts 02129 USAAbstract 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.https://doi.org/10.1002/acn3.52237
spellingShingle Eva A. Krijnen
Hansol Lee
Samantha Noteboom
Florence L. Chiang
Martijn D. Steenwijk
Menno M. Schoonheim
Eric C. Klawiter
Susie Y. Huang
In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis
Annals of Clinical and Translational Neurology
title In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis
title_full In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis
title_fullStr In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis
title_full_unstemmed In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis
title_short In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis
title_sort in vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis
url https://doi.org/10.1002/acn3.52237
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