Myelin is a protein complex which plays an integral role in developing and maintaining proper brain function. Due to the plasticity of the brain, and the dynamic nature of myelin, it is critical to develop methods that allow for the investigation of changes in myelin in vivo, to further our understanding of the brain. A substantial amount of myelin is found in the grey matter (GM) of the cerebral cortex – the outermost structure of the brain that supports higher order functions including cognition and more fundamental functions, such as sensation and motor control. While in vivo investigations have traditionally used imaging to focus on myelin in the deep white matter (WM) tracts in the brain, advances in magnetic resonance imaging (MRI) are now allowing investigations of intracortical myelin (ICM). The research in this thesis presents methodology for investigating intracortical myelin levels using magnetic resonance imaging (MRI) in humans, with the aim of developing a better understanding of how myelin contributes to healthy cortical function, and how it may be disrupted in disease.
To characterize intracortical myelin, a novel MRI analysis technique was developed early in this work to report the thickness of the heavily myelinated and lightly myelinated layers of the cortex. This measure of myelinated cortical thickness uses a clustering algorithm to separate the layers of the cortex based on voxel intensity in a T1- weighted (T1W) MRI with strong intracortical contrast. The resulting myelinated thickness maps match known myelin profiles of the brain, with cortical regions such as the primary visual and motor cortices displaying proportionally thicker, heavily myelinated layers. The utility of the myelinated cortical thickness for answering clinical questions was tested in bipolar disorder, where a preferential loss of the more myelinated layers in the dorsal lateral prefrontal cortex was found. This study provided the first in vivo evidence of ICM disruptions in bipolar disorder.
Later in the thesis work, after surface-based analysis techniques became available, an alternative approach to investigate intracortical myelin was developed that sampled the T1W image intensity at a calculated depth of the cortex as a measure of myelin content. This methodology was used for studying the association of ICM with age in healthy adults ranging from late adolescence to middle-adulthood. It was found that three cortical depths followed a similar trajectory through this age-span, reaching their peak between 35 and 40 years of age. This study contributes to a picture of ICM amounts increasing well into middle age in healthy adults and provides a baseline for studies investigating how this may be disrupted in disease
Up to this point, the analysis in the thesis used a specialized T1W MRI that had been optimized to provide strong intracortical contrast, but a question remained of how useful the technique would be if more commonly collected clinical MRIs were used as inputs. This analysis was thus applied to standard T1W and T2-weighted (T2W) anatomical MRIs to test its clinical applicability. 360 participants were investigated from the TRACK-HD dataset to test if intracortical signal analysis could follow the progression of Huntington’s disease. A significant increase in intracortical T1W/T2W signal was found in the most advanced disease group in several cortical regions. This increase in intracortical signal is likely tracking a known increase in iron and/or myelin levels in the Huntington’s disease brain. However, this work suggests that ICM studies would best be conducted with optimized imaging to better be able to characterize the subtle ICM variations within the GM.
Overall, the work in this thesis presents two techniques for whole-brain mapping of the distribution of intracortical myelin using MRI. The clinical applicability of the techniques was demonstrated in examples of mental and neurodegenerative disorders. The future directions of this work include developing imaging specific to either myelin or iron as well as revisiting these problems while imaging at greater resolution to better characterize the laminar profile across the cortex. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23655 |
| Date | January 2018 |
| Creators | Rowley, Christopher |
| Contributors | Bock, Nicholas, Neuroscience |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0015 seconds