Multi-Modal Microstructural Imaging of Brain White Matter

Mariam Andersson

Research output: Book/ReportPh.D. thesis

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Abstract

The diameters of axons, the communication cables of the brain, determine the conduction velocity at which signals are communicated within the brain network. Some neurodegenerative diseases manifest as damage to axons of a particular size, and axon diameter is thus an indicator of brain health and a potential biomarker of disease. Diffusion magnetic resonance imaging (MRI) methods can non-invasively provide estimates of axon diameter in the living brain, but many rely on the assumption that axons can be described as cylindrical. Imaging white matter regions of the vervet monkey brain with synchrotron XRay Nano-Holotomography reveals how blood vessels, cell clusters and vacuoles modulate the three-dimensional morphologies of axons. The findings challenge current knowledge of the signal conduction process in axons and shed light on the validity of enforcing a cylindrical axon shape in biophysical models. Axonal connections could be traced with structure tensor tractography on X-ray nanotomography images of healthy and diseased tissue from the mouse brain, providing a characterisation of the macroscopic organisation of axonal bundles. Experiments using x-ray nanotomography on the hydrated genu of the vervet monkey brain revealed features that were difficult to distinguish in samples treated with conventional sample processing techniques involving dehydration, indicating a need to image the hydrated white matter environment. Lastly, powder average approaches to axon diameter estimation with diffusion
MRI were validated using segmented axons from a crossing fibre and splenium region of the vervet monkey brain. Even in extremely complex white matter architectures, accurate estimates of axon diameter could be obtained for different sequence parameters and diffusion times. At sufficiently low b-values, the acquisition was sensitive to axonal microdispersion and the intra-axonal parallel
diffusivity showed time dependence, which could be an interesting biomarker of white matter health and pathology. Ultimately, the signal-to-noise ratio determined the range of measurable axon diameter.
Original languageEnglish
PublisherTechnical University of Denmark
Number of pages211
Publication statusPublished - 2021

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