Myelin and axon pathology in multiple sclerosis assessed by myelin water and multi-shell diffusion imaging

Autor: Matthias Weigel, Sabine Schaedelin, Thanh D. Nguyen, M. Absinta, Po Jui Lu, Ludwig Kappos, Jens Kuhle, Meritxell Bach Cuadra, Francesco La Rosa, Simona Schiavi, Pascal Sati, Pietro Maggi, Alessandro Daducci, Cristina Granziera, Daniel S. Reich, Muhamed Barakovic, Yi Wang, Ernst Wilhelm Radue, Reza Rahmanzadeh
Přispěvatelé: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie
Rok vydání: 2021
Předmět:
Male
Pathology
Adult
Axons/pathology
Brain/diagnostic imaging
Brain/pathology
Diffusion Magnetic Resonance Imaging/methods
Female
Humans
Image Interpretation
Computer-Assisted/methods
Middle Aged
Multiple Sclerosis/diagnostic imaging
Multiple Sclerosis/pathology
Myelin Sheath/pathology
Neuroimaging/methods
Water
demyelination
diffusion microstructural modelling
multiple sclerosis
myelin water imaging
neurodegeneration
lesions
030218 nuclear medicine & medical imaging
Myelin
Computer-Assisted
gray-matter
0302 clinical medicine
Axon
Myelin Sheath
AcademicSubjects/SCI01870
Brain
3. Good health
medicine.anatomical_structure
medicine.medical_specialty
Multiple Sclerosis
Neurite
injury
Neuroimaging
Grey matter
White matter
03 medical and health sciences
Image Interpretation
Computer-Assisted
normal-appearing white
medicine
magnetization-transfer ratio
Remyelination
Image Interpretation
disease
business.industry
Multiple sclerosis
Original Articles
medicine.disease
Axons
Hyperintensity
remyelination
Diffusion Magnetic Resonance Imaging
disability
nervous system
AcademicSubjects/MED00310
Neurology (clinical)
business
neurite orientation dispersion
030217 neurology & neurosurgery
Zdroj: Brain
Brain, vol. 144, no. 6, pp. 1684-1696
Brain, Vol. 144, no. 6, p. 1684-1696 (2021)
ISSN: 1460-2156
0006-8950
DOI: 10.1093/brain/awab088
Popis: Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging.
We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage. Ninety-one multiple sclerosis patients (62 relapsing-remitting, 29 progressive) and 72 healthy controls were enrolled in the study.
Differences in myelin water fraction and neurite density index were substantial when lesions were compared to healthy control subjects and normal-appearing multiple sclerosis tissue: both white matter and cortical lesions exhibited a decreased myelin water fraction and neurite density index compared with healthy (P < 0.0001) and peri-plaque white matter (P < 0.0001). Periventricular lesions showed decreased myelin water fraction and neurite density index compared with lesions in the juxtacortical region ( P < 0.0001 and P < 0.05). Similarly, lesions with paramagnetic rims showed decreased myelin water fraction and neurite density index relative to lesions without a rim (P < 0.0001). Also, in 75% of white matter lesions, the reduction in neurite density index was higher than the reduction in the myelin water fraction. Besides, normal-appearing white and grey matter revealed diffuse reduction of myelin water fraction and neurite density index in multiple sclerosis compared to healthy controls (P < 0.01). Further, a more extensive reduction in myelin water fraction and neurite density index in normalappearing cortex was observed in progressive versus relapsing-remitting participants. Neurite density index in white matter lesions correlated with disability in patients with clinical deficits (P < 0.01, beta = -10.00); and neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patient cohort (P < 0.01, beta = -3.60 and P < 0.01, beta = 0.13, respectively).
These findings suggest that (i) myelin and axon pathology in multiple sclerosis is extensive in both lesions and normal-appearing tissue; (ii) particular types of lesions exhibit more damage to myelin and axons than others; (iii) progressive patients differ from relapsing-remitting patients because of more extensive axon/myelin damage in the cortex; and (iv) myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage.
Databáze: OpenAIRE
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