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Quantitative Magnetic Resonance Imaging in Multiple Sclerosis: Neuropathology and Genetics Correlates

Rahmanzadeh, Reza. Quantitative Magnetic Resonance Imaging in Multiple Sclerosis: Neuropathology and Genetics Correlates. 2022, Doctoral Thesis, University of Basel, Faculty of Medicine.

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Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterized by multifocal inflammatory infiltrates, microglial activation and degradation of oligodendrocytes, myelin and axons. The imbalance between the damage to the myelin/axonal structure and axonal repair is considered to be one of the drivers of disability in MS patients. MS patients exhibit a high heterogeneity in disease progression and in the extent of myelin/axonal damage and the underlying mechanisms are currently poorly understood. Hence, the overall goals & findings of this doctoral thesis were:
i) to study the interplay between myelin and axonal damage/repair in various MS lesion types and different brain regions using myelin water imaging for myelin water fraction (MWF) and multi-shell diffusion imaging. Our findings showed that particular lesion types (e.g. paramagnetic rim lesions & periventricular lesions) exhibit more damage to myelin and axons, and myelin and axon pathology in lesions is related to MS disability and global measures of neuroaxonal damage.
ii) to propose a new approach to distinguish MS lesion types using clinically-compatible qMRI techniques. In a cross-sectional/longitudinal in vivo study with post-mortem verification, we have shown that quantitative susceptibility mapping (QSM) could identify remyelinated, chronic active and chronic inactive MS lesions with high accuracy.
iii) to evaluate the reproducibility of MWF, QSM, quantitative T1 mapping (qT1), magnetization transfer saturation imaging (MTsat). and their relative sensitivity to MS pathology. Our findings showed that quantitative magnetic resonance imaging (qMRIs) exhibit differential sensitivity to focal and diffuse WM and GM pathology in MS patients and are highly reproducible.
iv) to study the relationship between genetic risk factors and myelin/axonal damage/repair in MS. Our study identified novel genetic loci that might be associated with myelin and axonal pathology in MS Patients.
Advisors:Granziera, Cristina
Committee Members:Cichon, Sven and Inglese, Matilde
Faculties and Departments:03 Faculty of Medicine
UniBasel Contributors:Cichon, Sven
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14684
Thesis status:Complete
Number of Pages:142
Language:English
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss146842
edoc DOI:
Last Modified:01 Jan 2024 02:30
Deposited On:18 May 2022 08:12

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