Cortical structure: Linking MRI and cytoarchitecture

Change log

MRI provides a powerful tool to investigate brain structure in living humans. However a major challenge is interpreting the biological underpinnings of changes at this scale. This dissertation describes investigations into the problem of linking microscale post mortem cortical cytoarchitecture with millimeter-scale measures of cortical anatomy accessible through in vivo MRI.

Chapter 1 introduces the problem and previous work done to address it. The following two chapters apply classical atlases of cortical cytoarchitecture to understanding morphological changes both in health (Chapter 2) and in disease (Chapter 3). Chapter 2 demonstrates that sensory processing hierarchies exhibit increasing gradients of cortical thickness, related to changes in cortical cytoarchitecture. In Chapter 3, cytoarchitectonically described differences in gyral and sulcal laminar structure were used to create markers of laminar change from MRI changes in schizophrenia.

Classical measurements of histology have limitations; they are observer dependent, two-dimensional with limited coverage of the cortex. To address these issues, Chapters 4-6 document work carried on BigBrain, a 3D 20μm resolution histological dataset. I created a high-resolution 3D atlas of laminar cytoarchitecture, which was mapped to MRI-compatible cortical surface reconstructions. Chapter 4 records the development of an automated 1D profile-based approach to laminar analysis, revealing basic principles of cortical cytoarchitecture. In Chapter 5 this approach was extended to identify 6 cortical layers throughout the isocortex. These tools can be used to segment 1D cortical intensity profiles derived from any modality. In Chapter 6, the analysis of cortical gradients initially identified using MRI cortical thickness in Chapter 2 was replicated and extended using novel histological data. First histological cortical thicknesses were tested for the same patterns organization measured on in vivo MRI in Chapter 2. These analyses were extended to test which layers contributed most to overall thickness. High-resolution, complete maps of cortical cytoarchitecture mapped to MRI-template cortical surface reconstructions, are a powerful tool and dataset for the neuroimaging community. They offer new possibilities for linking cortical microstructure to in vivo neuroimaging.

Fletcher, Paul
MRI, Cytoarchitecture, Cortex
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge