Advances in Diffusion Magnetic Resonance Imaging with Application to Multiple Sclerosis

• Author / Creator

  Valdés Cabrera, Diana

• Multiple Sclerosis (MS) is a chronic neurodegenerative disease which is mainly characterized by inflammation, demyelination, and axonal loss. Conventional Magnetic Resonance Imaging (MRI) has become the most established imaging tool in the diagnosis and follow-up of MS in clinical practice. However, the high sensitivity of these standard MRI techniques is mainly restricted to the detection of focal demyelinating MS lesions, mainly in white matter (WM), as they fail to depict further damage in normal appearing WM (NAWM) and grey matter (GM) involvement. More advanced quantitative MRI methods, including diffusion MRI, have been applied in MS research and they have improved the detection and interpretation of heterogeneous MS pathologic features in lesions and in normal-appearing brain tissue. Abnormal diffusion tensor imaging (DTI) metrics, although not fully pathologically specific, have helped characterize the disease burden with progression and they have shown correlations with several disability and cognitive measures in MS. So far, MS DTI studies with consistent results and interpretations are still uncommon in the clinical practice. Furthermore, research diffusion MRI studies properly targeting small brain structures such as the limbic system WM and deep GM, or even areas with crossing fibers in MS are also rare and show conflicting results. This is largely because these experiments require careful considerations regarding acquisition protocols (e.g., high spatial resolution, imaging artifacts) and post-processing strategies (e.g., eddy currents correction, tensor fitting, higher order models).
  This thesis aims to address these MS literature gaps and limitations by using advanced diffusion MRI methods in two cross sectional datasets of individuals diagnosed with MS over four chapters, the first in cohort 1 at 4.7 T and the final three in cohort 2 at 3 T: (i) high resolution DTI tractography of limbic WM tracts, (ii) CSF-suppressed DTI tractography of the fornix, (iii) high
  iii
  resolution DTI of the hippocampus, and (iv) novel b-tensor encoding diffusion MRI in lesions and NAWM. Data presented here reveal new information on how small WM and GM structures such as the fornix and the hippocampus, which are linked to cognitive and mood disorders in several neurodegenerative diseases, appear to be affected early and consistently in MS regardless of the patient’s phenotypic classification and disability status. Cross sectional analyses in the two MS cohorts studied here reveal robust reductions of fornix volume and abnormal diffusion metrics such as low fractional anisotropy (FA) and higher mean (MD), axial (AD), and radial (RD) diffusivities when compared to controls. Other affected limbic areas in terms of atrophy or microstructure include the uncinate fasciculus, thalamus and hippocampus, with fornix RD and thalamus atrophy standing out as predictors of cognitive impairment in MS. Hippocampus atrophy, abnormal diffusion metrics and long T2 values are reported in MS patients with cognitive impairment (CI), while greater regional mean diffusivity (MD), potentially indicative of demyelination, is evident in MS subjects independent of their CI status when compared to controls. This regional hippocampus analysis shows elevated MD and T2 relaxometry values, which are variable and widespread in MS, greater in patients with CI and high lesion volume, and linked with disability in the case of T2 relaxometry. In addition, b-tensor diffusion metrics complement standard metrics, and they differ between lesions and NAWM and between different WM fiber configurations in MS and controls. In conclusion, this thesis outlines a repertoire of advanced diffusion MRI methods, which has shown important insight about the limbic system microstructural changes as well as lesion and NAWM alterations in MS and their relationships with memory and behaviour.

• Subjects / Keywords

  • MRI
  • diffusion
  • DTI
  • multiple sclerosis
  • demyelination
  • memory

• Graduation date

  Fall 2022

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-cq79-mb21

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.