Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease‐related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders

The neuropathology of the social cognitive network in autism

Potential differences in developmental trajectory were investigated in autism at both the macro- and micro-scopic scale, using regional volumetric measurements from in-vivo scans and measurements of minicolumnar organisation of the cortex in post-mortem tissue. In addition, a study was carried out to investigate the sensitivity of measures of cortical diffusion to cortical architecture. Three key regions of interest were studied throughout this thesis, orbital frontal cortex (BA11), primary auditory cortex (BA41) and part of the inferior parietal lobe (BA40). Subjects with ASD showed increases in grey matter in left parietal cortex and decreases in left BA11 compared to controls. In addition, subjects with ASD showed increased grey matter volume with age in both BA41 and the inferior parietal lobe, whereas controls only showed a negative correlation between grey matter volume in BA41 and age. Wider minicolumns were found in ASD in all regions, suggesting pathology is not restricted to higher order association areas. Differences seemed more pronounced at younger ages suggesting an altered developmental trajectory in ASD. Such an increase in minicolumnar width arguably underlies the feature-based processing style seen in ASD. A pilot study using post-mortem DTI scans of MS brains revealed a relationship between measures of the directionality of diffusion and the width of axonal bundles in the cortex, an aspect of the minicolumnar arrangement. When extending this investigation to a set of ASD and control brains, evidence was found for different relationships between axon bundle width and measures of the directionality of diffusion in the cortex, suggesting that although differences in axon bundle width were not seen between groups, there may be differences in the composition of the axon bundles between ASD and control groups.</p

The neuropathology of the social cognitive network in autism

Potential differences in developmental trajectory were investigated in autism at both the macro- and micro-scopic scale, using regional volumetric measurements from in-vivo scans and measurements of minicolumnar organisation of the cortex in post-mortem tissue. In addition, a study was carried out to investigate the sensitivity of measures of cortical diffusion to cortical architecture. Three key regions of interest were studied throughout this thesis, orbital frontal cortex (BA11), primary auditory cortex (BA41) and part of the inferior parietal lobe (BA40). Subjects with ASD showed increases in grey matter in left parietal cortex and decreases in left BA11 compared to controls. In addition, subjects with ASD showed increased grey matter volume with age in both BA41 and the inferior parietal lobe, whereas controls only showed a negative correlation between grey matter volume in BA41 and age. Wider minicolumns were found in ASD in all regions, suggesting pathology is not restricted to higher order association areas. Differences seemed more pronounced at younger ages suggesting an altered developmental trajectory in ASD. Such an increase in minicolumnar width arguably underlies the feature-based processing style seen in ASD. A pilot study using post-mortem DTI scans of MS brains revealed a relationship between measures of the directionality of diffusion and the width of axonal bundles in the cortex, an aspect of the minicolumnar arrangement. When extending this investigation to a set of ASD and control brains, evidence was found for different relationships between axon bundle width and measures of the directionality of diffusion in the cortex, suggesting that although differences in axon bundle width were not seen between groups, there may be differences in the composition of the axon bundles between ASD and control groups.This thesis is not currently available in OR

Wider minicolumns in autism: a neural basis for altered processing?

Previous studies have found alterations in the columnar organization of the cortex in autism spectrum disorders. Such changes have been suggested to be limited to higher order association areas and to spare primary sensory areas. In addition, evidence from gene-expression studies have suggested that there may be an attenuation of cortical differentiation in autism spectrum disorders. The present study specifically assessed the minicolumns of cells that span the depth of the cortex in a larger sample of autism spectrum disorder cases than have been studied previously, and across a broad age range. The cortical regions to be investigated were carefully chosen to enable hypotheses about cortical differentiation and the vulnerability of association cortex to be tested. Measures of the minicolumnar arrangement of the cortex (minicolumn width, spacing and width of the associated axon bundles) were made in four regions of cortex (primary auditory cortex, auditory association cortex, orbital frontal cortex and inferior parietal lobe) for 28 subjects with autism spectrum disorder and 25 typically developing control subjects. The present study found wider minicolumns in autism spectrum disorder [F(1,28) = 8.098, P = 0.008], which was particularly pronounced at younger ages, providing evidence for an altered developmental trajectory at the microstructural level. In addition, altered minicolumn width was not restricted to higher order association areas, but was also seen in the primary sensory region investigated. Finally, this study found evidence that cortical regional differentiation was still present in autism spectrum disorder [F(3,39) = 5.486, P = 0.003], although attenuated compared to typically developing subjects [F(3,45) = 18.615, P < 0.001]. It is suggested that wider spacing of the minicolumns may relate to the enhanced discrimination seen in some individuals with autism spectrum disorder

Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease‐related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders

Implementing a nurse-enabled, integrated, shared-care model involving specialists and general practitioners in breast cancer post-treatment follow-up: a study protocol for a phase II randomised controlled trial (the EMINENT trial)

Background: Due to advances in early detection and cancer treatment, 5-year relative survival rates for early breast cancer surpass 90% in developed nations. There is increasing focus on promotion of wellness in survivorship and active approaches to reducing morbidity related to treatment; however, current models of follow-up care are heavily reliant on hospital-based specialist-led care. This study aims to test the feasibility of the EMINENT intervention for implementing an integrated, shared-care model involving both cancer centre specialists and community-based general practitioners for early breast cancer post-treatment follow-up. Methods: We describe a protocol for a phase II, randomised controlled trial with two parallel arms and 1:1 allocation. A total of 60 patients with early-stage breast cancer will be randomised to usual, specialist-led, follow-up care (as determined by the treating surgeons, medical oncologists, and radiation oncologists) or shared follow-up care intervention (i.e. EMINENT). EMINENT is a nurse-enabled, pre-specified shared-care pathway with follow-up responsibilities divided between cancer centre specialists (i.e. surgeons and oncologists) and general practitioners. The primary outcome is health-related quality of life as measured by the Functional Assessment of Cancer Therapy—Breast Cancer. Secondary outcomes include patient experience, acceptance, and satisfaction of care; dietary, physical activity, and sedentary behaviours; financial toxicity; adherence; health resource utilisation; and adverse events. Discussion: The trial is designed to identify the barriers to implementing a shared-care model for breast cancer survivors following treatment. Results of this study will inform a definitive trial testing the effects of shared-care model on health-related quality of life of breast cancer survivors, as well as its ability to alleviate the growing demands on the healthcare system. Trial registration: Australia and New Zealand Clinical Trials Registry ACTRN12619001594112. Registered on 19 November 201