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1
Mussie, Ezana. "Dark Matter, White Space." Thesis, Malmö universitet, Fakulteten för kultur och samhälle (KS), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-21571.
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This thesis addresses the ambiguous role of Malmö’s latest megaproject in the context of the city’s racializing urban development trajectory. The project is a public/private congress center, concert hall and hotel complex called Malmö Live. Malmö Live is problematized as the height of spectacle and challenge as it is expected to be the city’s most prominent cultural and social meeting place. The inquiry is directed to how its expectation of relevancy came about and utilizes a Foucauldian inspired genealogical methodology. The result stems from an investigation of the historical, present, local and global conditions that constitutes the expectancy of its relevancy. The investigation notes the divisiveness of tourism and how it affects ways of thinking and doing government on multiple scales, and in particular how it motivates the case in question. The result shows that there are affinities between tourism- during-colonialism and the contemporary tourism industry. Where the former was appropriated by colonialism and overtly racializing, the latter is allowed appropriacy by a currency ascribed to selected geographies and histories. By describing the becoming of this megaproject and the use of tourism knowledge and technology, the how-question about the expectation of Malmö Live’s relevancy leads to a genealogical reconstruction of Malmö Live as a wager on whiteness. The wager on whiteness hold no guarantees, but the power of it is the ability to be persuasive and believed, and the currency it holds for those who perform it. The thesis ends with a discussion on what is at stake with Malmö Live, i.e. Malmö’s whiteness.
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Sparrow, Sarah Anne. "Neuroepigenetics of preterm white matter injury." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31230.
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Introduction: Preterm birth is increasing worldwide and is a major cause of neonatal death. Survivors are at increased risk of neurodisability, cognitive, social and psychiatric disorders in later life. Alterations to the white matter can be assessed using diffusion tensor imaging (DTI) MRI and are associated with poor neurodevelopmental outcome. The pathogenesis of white matter injury is multifactorial and several clinical risk and resilience factors have been identified. DNA methylation (DNAm) is an epigenetic process which links stressful early life experience to later life disease and is associated with normal brain development, neuronal processes and neurological disease. Several studies have shown DNAm is altered by the perinatal environment, however its role in preterm white mater injury is yet to be investigated. Aims: 1. To examine the relationship between preterm birth and white matter integrity 2. To investigate the effect of neuroprotective treatments and deleterious clinical states on white matter integrity in preterm infants 3. To assess the best DTI method of quantifying white matter integrity in a neonatal population 4. To investigate the effect of preterm birth on DNA methylation and 5. To determine the clinical and imaging factors that contribute to the variance in DNA Methylation caused by preterm birth Methods: DTI data was acquired from preterm infants (< 32 weeks' gestation or < 1500 grams at birth) at term equivalent age (TEA) and term controls (> 37 weeks' gestation at birth). Region-of-interests (ROI) and tract-averaged methods of DTI analysis were performed to obtain measurements of fractional anisotropy (FA) and mean diffusivity (MD) in the genu of corpus callosum, posterior limb of internal capsule and centrum semiovale. Clinical data was collected for all infants and the effect of prematurity, neuroprotective agents and clinical risk factors on white matter integrity were analysed. 8 major white matter tracts were segmented using probabilistic neighbourhood tractography (PNT), a tract-averaged technique which also allowed the calculation of tract shape. The two DTI techniques were compared to evaluate agreement between results. DNA was collected from preterm infants and term controls at TEA, and a genome-wide analysis of DNAm was performed. DTI parameters from probabilistic neighborhood tractography (PNT) methodology and clinical risk and resilience factors were used to inform a principal components analysis to investigate the contribution of white matter integrity and clinical variables to variance in DNAm. Results: FA and MD were significantly affected by preterm birth on ROI analysis. In addition, DTI parameters were affected by clinical factors that included antenatal magnesium sulphate, histological chorioamnionitis and bronchopulmonary dysplasia. Evaluation of DTI methodology revealed good accuracy in repeated ROI measurements but limited agreement with tract-averaged values. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants, compared with controls. 10 of these genes have a documented association with neural function or neurological disease. Differences detected in the array were validated with pyrosequencing which captured additional differentially methylated CpGs. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 principal components (PC); corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Conclusions: Preterm birth is associated with alterations in white matter integrity which is modifiable by clinical risk factors and neuroprotective agents. ROI analysis may not provide sufficient representation of white matter tracts in their entirety. Prematurity is related to alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for future work and contributed to the understanding of the pathogenesis of preterm brain injury.
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Russell-Schulz, Bretta Adrianne. "Characterizing T₂ distributions in healthy white matter." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/38369.
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Quantitative T₂ measurements in Magnetic resonance imaging (MRI) can provide information about water environments in biological structures. Here, an extended Carr-Purcell-Meiboom-Gill sequence (CPMG) with echoes out to 1120ms was used to characterize Long-T₂ times of healthy white matter in brain. One of the white matter structures, the corticospinal tract (CST), was previously found to be bright on T₂-weighted images and myelin water fraction (MWF) images. The intra-/extra- cellular water (IE) T₂ peak of the CST was found to be broadened in comparison to that from other white matter structures and often split into two distinct peaks. In the CST, it appeared that the intracellular and extracellular water environments had different T₂ times, causing the intracellular water peak to be pushed down into the myelin water T₂ regime and the extracellular peak to be pushed up to higher T₂ times. The conventional T₂ limits of 10−40ms used for the MWF at 1.5T result in an artificial increase in MWF, which causes the CST to be bright on myelin water images. When the upper limit of the MWF range was decreased to 25ms, the CST exhibited MWF values similar to those found for adjacent anterior and posterior regions.
Using T₂ time of 25ms for the myelin water (MW) upper limit and IE lower limit, a moderately strong relationship between IE geometric mean T₂ (GMT₂) and MW was found across all structures and subjects. This relationship did not necessarily hold when examined across subjects within individual structures The relationship between IE GMT₂ and MWF could arise from a non-biological source, such as the algorithm used in calculating T₂ or from a biological source, such as exchange between the water environments or increased extracellular water. Based on our results the fitting algorithm does not appear to be responsible for this relationship based on our results. However, either varying amounts of extracellular water or exchange between MW and IE could explain this relationship.
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Campbell, Jennifer S. W. "Diffusion imaging of white matter fibre tracts." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85135.
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This thesis presents the design and validation of a method for digitally reconstructing white matter fibre tracts in vivo using magnetic resonance imaging (MRI). The technique uses diffusion weighted MRI to estimate a likelihood distribution function for the fibre direction(s) in each imaging voxel, and subsequently infers connectivity from any point in the central nervous system to another. The fibre tracking algorithm addresses issues that can confound fibre tract reconstruction, such as imaging noise, subvoxel partial volume averaging of fibre directions, and problems with the estimate of the diffusion probability density function (pdf). It can take as input a diffusion pdf estimated using either the traditional diffusion tensor approach or more recent high angular resolution diffusion approaches. The fibre tracking technique is validated using in vivo human brain diffusion imaging data and using a phantom constructed from excised rat spinal cord, which provides a "gold standard" connectivity map. The results are promising, especially for regions of the brain where tracking using previously described algorithms has been difficult to perform, for example, the regions of complex fibre structure near the cortex. As the cortex is critical for functional activity in the brain, this may have widespread implications for our understanding of the human brain in healthy subjects and in disease.
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McCracken, Eileen. "White matter damage after acute brain injury." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340812.
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O'Donnell, Lauren Jean. "Cerebral white matter analysis using diffusion imaging." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/35514.
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Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006.Includes bibliographical references (p. 183-198).
In this thesis we address the whole-brain tractography segmentation problem. Diffusion magnetic resonance imaging can be used to create a representation of white matter tracts in the brain via a process called tractography. Whole brain tractography outputs thousands of trajectories that each approximate a white matter fiber pathway. Our method performs automatic organization, or segmention, of these trajectories into anatomical regions and gives automatic region correspondence across subjects. Our method enables both the automatic group comparison of white matter anatomy and of its regional diffusion properties, and the creation of consistent white matter visualizations across subjects. We learn a model of common white matter structures by analyzing many registered tractography datasets simultaneously. Each trajectory is represented as a point in a high-dimensional spectral embedding space, and common structures are found by clustering in this space. By annotating the clusters with anatomical labels, we create a model that we call a high-dimensional white matter atlas.
(cont.) Our atlas creation method discovers structures corresponding to expected white matter anatomy, such as the corpus callosum, uncinate fasciculus, cingulum bundles, arcuate fasciculus, etc. We show how to extend the spectral clustering solution, stored in the atlas, using the Nystrom method to perform automatic segmentation of tractography from novel subjects. This automatic tractography segmentation gives an automatic region correspondence across subjects when all subjects are labeled using the atlas. We show the resulting automatic region correspondences, demonstrate that our clustering method is reproducible, and show that the automatically segmented regions can be used for robust measurement of fractional anisotropy.
by Lauren Jean O'Donnell.
Ph.D.
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Morgan, G. L. "Regional variation models of white matter microstructure." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1379541/.
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Diffusion-weighted MRI (DW-MRI) is a powerful in vivo imaging technique that is particularly sensitive to the underlying microstructure of white matter tissue in the brain. Many models of the DW-MRI signal exist that allow us to relate the signals we measure to various aspects of the tissue structure, including measures of diffusivity, cellularity and even axon size. From histology, we know that many of these microstructure measures display distinct patterns of variation on length scales greater than the average voxel size. However very few methods exist that use this spatial coherence to inform and guide parameter estimation. Instead, most techniques treat each voxel of data independently. This is particularly problematic when estimating parameters such as axon radius which only weakly influence the signal, as the resulting estimates are noisy. Several methods have been proposed that spatially smooth parameter estimates after fitting the model in each voxel. However if the parameter estimates are very noisy, the underlying trend is likely to be obscured. These methods are also unable to account for spatial coupling that may exist between the various parameters. This thesis introduces a novel framework, the Regional Variation Model (RVM), which exploits the underlying spatial coherence within white matter tracts to estimate trends of microstructure variation across large regions of interest. We fit curves describing parameter variation directly to the diffusion-weighted signals which should capture spatial changes in a more natural way as well as reducing the effects of noise. This allows for more precise estimates of a range of microstructure indices, including axon radius. The resulting curves, which show how microstructure parameters vary spatially through white matter regions, can also be used to detect groupwise differences with potentially greater power than traditional methods.
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D'Anna, Lucio. "White matter disconnection in frontal lobe disorders." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/white-matter-disconnection-in-frontal-lobe-disorders(d3375b51-9431-4d54-bce3-62664bfbaff3).html.
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In the recent years our understanding of the frontal lobe functions has greatly advanced. The advances in the field of the neuropsychology, neuroimaging and neurosciences all contributed to a rapidly changing perspective on the role of the frontal lobes in behaviour and cognition and they also changed clinical approaches to the evaluation of patients with frontal lobe disorders. The structure of the brain can be non-invasively assessed in vivo using magnetic resonance imaging (MRI). The MRI diffusion tensor imaging (DTI) can be used to reconstruct the human brain white matter and to quantify their microstructural integrity. The aim of this thesis is to investigate the anatomy of the frontal networks underlying cognitive and behavioural functions and includes three studies: an investigation of the association between extra-motor white matter tracts and cognitive and behaviour symptoms in Motor Neuron Disease (MND); a study of the ventral fronto-temporal network and its association with behavioural symptoms in Primary Progressive Aphasia (PPA); a study to investigate the association between white matter abnormalities in several long association tracts and deficits in non-verbal and verbal communication in Autism Spectrum Disorders (ASD). Overall, the findings of this thesis indicate that both uncinate fasciculus and cingulum are frontal lobe structures particularly vulnerable to disease regardless the nature of the underlying pathology. Damage to these tracts could manifest with abnormalities in several aspects of social behaviour and cognition. These considerations will help to broaden our understanding of the frontal lobe function beyond motor and language functions.
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Doyle, Seán P. "Excitotoxic injury mechanisms in central white matter." Thesis, University of Plymouth, 2017. http://hdl.handle.net/10026.1/9586.
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Myelinated axons are crucial for rapid information transmission within the central nervous system (CNS). Myelin injury is a common feature of white matter (WM) pathology in a number of disease states, including ischemic stroke. Myelin disruption can lead to a complete failure in saltatory action potential conduction, resulting in devastating neurological deficits. However, the fundamental mechanism of ischemic myelin injury is controversial. Glutamate-mediated excitotoxicity is now recognised as a crucial event in the development of ischemic WM pathology. This thesis investigates the potential mechanisms of glutamate release in central WM and examines the hypothesis that NMDA receptor over-activation mediates ischemic myelin damage. Using glutamate biosensor microelectrodes and FM-dye imaging, I show that axonal depolarisation in the adult corpus callosum evokes rapid vesicular docking in axons, capable of elevating extracellular glutamate concentration. My findings show that vesicular fusion occurs under the myelin sheath in myelinated axons, which supports the existence of a novel synapse between the axon and overlaying myelin. Simulation of ischemia triggered an early and robust rise in optic nerve extracellular glutamate levels. Unexpectedly, a significant component of ischemic glutamate release also originated from axonal vesicular fusion. Together, these findings show that the axon-myelin synapse represents a significant site of excitotoxic injury during ischemia. Resolving prior conflicting results, I show that NMDA receptor antagonists prevent myelin degradation and improve functional recovery when applied for sufficient time to penetrate the sheath. Finally, I identify a fluorescent myelin stain (QNZ-46) which is a negative allosteric modulator of NR2C/D-containing NMDA receptors. QNZ-46 selectively accumulates in myelinated WM regions of the CNS following systemic administration, and is retained following wash-out. As a result, QNZ-46 provides persistent protection during ischemia by preserving myelin structure and improving functional recovery.
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Bertò, Giulia. "Supervised Learning for White Matter Bundle Segmentation." Doctoral thesis, Università degli studi di Trento, 2020. http://hdl.handle.net/11572/264971.
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Accurate delineation of anatomical structures in the white matter of the human brain is of paramount importance for multiple applications, such as neurosurgical planning, characterization of neurological disorders, and connectomic studies. Diffusion Magnetic Resonance Imaging (dMRI) techniques can provide, in-vivo, a mathematical representation of thousands of fibers composing such anatomical structures, in the form of 3D
polylines called streamlines. Given this representation, a task of invaluable interest is known as white matter bundle segmentation, whose aim is to virtually group together streamlines sharing a similar pathway into anatomically meaningful structures, called white matter bundles.
Obtaining a good and reliable bundle segmentation is however not trivial, mainly because of the intrinsic complexity of the data. Most of the current methods for bundle segmentation require extensive neuroanatomical knowledge, are time consuming, or are not able to adapt to different data settings. To overcome these limitations, the main goal of this thesis is to develop a new automatic method for accurate white matter bundle segmentation, by exploiting, combining and extending multiple up-to-date supervised learning techniques.
The main contribution of the project is the development of a novel streamline-based bundle segmentation method based on binary linear classification, which simultaneously combines information from atlases, bundle geometries, and connectivity patterns. We prove that the proposed method reaches unprecedented quality of segmentation, and that is robust to a multitude of diverse settings, such as when there are differences in bundle size, tracking algorithm, and/or quality of dMRI data. In addition, we show that some of the state-of-the-art bundle segmentation methods are deeply affected by a geometrical property of the shape of the bundles to be segmented, their fractal dimension.
Important factors involved in the task of streamline classification are: (i) the need for an effective streamline distance function and (ii) the definition of a proper feature space. To this end, we compare some of the most common streamline distance functions available in the literature and we provide some guidelines on their practical use for the task of supervised bundle segmentation. Moreover, we investigate the possibility to include, in a streamline-based segmentation method, additional information to the typically employed streamline distance measure. Specifically, we provide evidence that considering additional anatomical information regarding the cortical terminations of the streamlines and their proximity to specific Regions of Interest (ROIs) helps to improve the results of bundle segmentation.
Lastly, significant attention is paid to reproducibility in neuroscience. Following the FAIR (Findable, Accessible, Interoperable and Reusable) Data Principles, we have integrated our pipelines of analysis into an online open platform devoted to promoting reproducibility of scientific results and to facilitating knowledge discovery.
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Bertò, Giulia. "Supervised Learning for White Matter Bundle Segmentation." Doctoral thesis, Università degli studi di Trento, 2020. http://hdl.handle.net/11572/264971.
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Accurate delineation of anatomical structures in the white matter of the human brain is of paramount importance for multiple applications, such as neurosurgical planning, characterization of neurological disorders, and connectomic studies. Diffusion Magnetic Resonance Imaging (dMRI) techniques can provide, in-vivo, a mathematical representation of thousands of fibers composing such anatomical structures, in the form of 3D
polylines called streamlines. Given this representation, a task of invaluable interest is known as white matter bundle segmentation, whose aim is to virtually group together streamlines sharing a similar pathway into anatomically meaningful structures, called white matter bundles.
Obtaining a good and reliable bundle segmentation is however not trivial, mainly because of the intrinsic complexity of the data. Most of the current methods for bundle segmentation require extensive neuroanatomical knowledge, are time consuming, or are not able to adapt to different data settings. To overcome these limitations, the main goal of this thesis is to develop a new automatic method for accurate white matter bundle segmentation, by exploiting, combining and extending multiple up-to-date supervised learning techniques.
The main contribution of the project is the development of a novel streamline-based bundle segmentation method based on binary linear classification, which simultaneously combines information from atlases, bundle geometries, and connectivity patterns. We prove that the proposed method reaches unprecedented quality of segmentation, and that is robust to a multitude of diverse settings, such as when there are differences in bundle size, tracking algorithm, and/or quality of dMRI data. In addition, we show that some of the state-of-the-art bundle segmentation methods are deeply affected by a geometrical property of the shape of the bundles to be segmented, their fractal dimension.
Important factors involved in the task of streamline classification are: (i) the need for an effective streamline distance function and (ii) the definition of a proper feature space. To this end, we compare some of the most common streamline distance functions available in the literature and we provide some guidelines on their practical use for the task of supervised bundle segmentation. Moreover, we investigate the possibility to include, in a streamline-based segmentation method, additional information to the typically employed streamline distance measure. Specifically, we provide evidence that considering additional anatomical information regarding the cortical terminations of the streamlines and their proximity to specific Regions of Interest (ROIs) helps to improve the results of bundle segmentation.
Lastly, significant attention is paid to reproducibility in neuroscience. Following the FAIR (Findable, Accessible, Interoperable and Reusable) Data Principles, we have integrated our pipelines of analysis into an online open platform devoted to promoting reproducibility of scientific results and to facilitating knowledge discovery.
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Fryer, Kirsty Laura. "Adverse effects of antidepressants in central white matter." Thesis, University of Nottingham, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.717072.
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Major depressive disorder (depression) is a significant, recurrent disorder, affecting over 350 million people worldwide. Often having a detrimental effect on quality of life, daily functioning, medical morbidity, and mortality it is one of the leading causes of disability worldwide. Depression pathology is little understood, and so treatments are often a 'stab in the dark'. Currently the most widely prescribed pharmacological treatment for depression is a group of antidepressants named the SSRIs (Selective Serotonin Reuptake Inhibitors), however their effectiveness over placebo is hotly debated. It may be that these drugs give a sense of hope where there was once hopelessness. Patients may be prescribed these drugs over decades, but no longitudinal studies on their prolonged side effects have been undertaken. With an aging population disturbing research on elderly patients taking these drugs showed an increase in white matter lesions compared to drug naive patients. White matter lesions have been indicated in various degenerative disorders, but as yet no studies have discussed the potential mechanism(s) of the SSRIs on white matter. This thesis explores the effect of various SSRIs, in particular fluoxetine (Prozac), on white matter using the rodent optic nerve (ON) as a model. Acute fluoxetine application had a concentration dependant effect, attenuating the compound action potential (CAP) evoked from the ON. These effects caused both decrease in peak area at high concentrations, and increased peak latency at lower concentrations. Similar effects were seen with other SSRIs, but not with a novel antidepressant, tianeptine, of the selective serotonin reuptake enhancer (SSRE) class. Chronic fluoxetine application caused a decreased CAP area, and a loss of the smallest and fastest conducting axons in the ON. Morphologically, fluoxetine has a clear effect on both myelin and the axons within the ON, causing damage similar to that seen during metabolic insult. Further exploration of the effects of fluoxetine show it is clearly a pharmacologically 'dirty drug', most likely acting on ion channels and oxidative metabolism; effects unrelated to its action as a SSRI. This study is a novel exploration into unchartered territory, where little prior research is available, but the findings encourage further exploration into SSRIs and their potential short and long term effects in white matter.
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Schiavone, Francesca. "Age related white matter changes and neuropsychological correlates." Thesis, St George's, University of London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511960.
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Fernando, Malee Samanmali. "Cerebral white matter lesions in the ageing brain." Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398598.
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Vergani, Francesco. "White matter fibres dissection in the human brain." Thesis, University of Newcastle upon Tyne, 2016. http://hdl.handle.net/10443/3503.
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Introduction: lesion to white matter fibres can induce permanent neurological deficits due to the induction of disconnection syndromes. Knowledge of white matter fibre anatomy is therefore relevant to the neurosurgeon in order to minimise the risk of causing neurological damage when approaching lesions in eloquent areas of the brain. Aim: to investigate the 3D anatomy of white matter fibres with particular attention to the associative tracts, including short arcuate fibres and intralobar fibres. The results obtained will be used to provide insights in brain connectivity, delineating networks important for specific brain functions. Methods: The Klingler technique for white matter dissection was followed. Brain specimens were collected and prepared at the Newcastle Brain Tissue Resource, Newcastle University. Brains were initially fixed in 10% formalin for at least 4 weeks. After removing the pia-mater and arachnoid, the brains were frozen at -15C° for 2 weeks. The water crystallisation induced by the freezing process separates the white matter fibres, facilitating the dissection of the tracts. Dissection was performed with wooden spatulas and blunt metallic dissectors, removing the cortex and exposing the white matter. The short associative (U-shaped) fibres were initially exposed. Long associative, commissural and projection fibres were demonstrated as the dissection proceeded. Results: five papers form the main body of the present work: 1) “Raymond de Vieussens and his contribution to the study of white matter anatomy”. This historical paper reviewed the history of white matter dissection, focusing on the work of Raymond de Vieussens, who gave the first account of the centrum ovale and of the continuity of the corticospinal tract from the centrum ovale to the brainstem. 2) “The white matter of the human cerebrum: part I The occipital lobe by Heinrich Sachs “ ; 3) “Intralobar fibres of the occipital lobe: A post mortem dissection study”. These joint papers were dedicated to the white matter anatomy of the occipital lobe. A rich network of association fibres, arranged around the ventricular wall, was demonstrated. A new white matter tract, connecting the cuneus to the lingula, was also described. Our original data I II were compared to the atlas of occipital fibres produced by the German anatomist Heinrich Sachs. 4) “White matter connections of the Supplementary Motor Area (SMA) in humans”. This study demonstrated that the SMA shows a wide range of connections with motor, language and limbic areas. Features of the SMA syndrome (akinesia and mutism) can be better understood on the basis of these findings. 5) “Anatomical connections of the Subgenual Cingulate Region” (SCG). This study showed that the SCG is at the centre of a large network, connecting prefrontal, limbic and mesotemporal regions. The connectivity of this region can help explain the clinical effect of neuromodulaton of the SCG in Deep Brain Stimulation for neuropsychiatric disorders. Conclusions: Klingler dissection provided original data about the connections of different brain regions that are relevant to neurosurgical practice, along with the description of a new white matter tract, connecting the cuneus to the lingula.
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Ordway, Gregory A. "White Matter Oligodendrocyte Pathology in Depression and Suicide." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/8673.
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Bennett, Ilana Jacqueline. "Aging, implicit sequence learning, and white matter integrity." Connect to Electronic Thesis (CONTENTdm), 2009. http://worldcat.org/oclc/463286305/viewonline.
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Sudre, C. H. "Automated segmentation and characterisation of white matter hyperintensities." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1522365/.
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Neuroimaging has enabled the observation of damage to the white matter that occurs frequently in elderly population and is depicted as hyperintensities in specific magnetic resonance images. Since the pathophysiology underlying the existence of these signal abnormalities and the association with clinical risk factors and outcome is still investigated, a robust and accurate quantification and characterisation of these observations is necessary. In this thesis, I developed a data-driven split and merge model selection framework that results in the joint modelling of normal appearing and outlier observations in a hierarchical Gaussian mixture model. The resulting model can then be used to segment white matter hyperintensities (WMH) in a post-processing step. The validity of the method in terms of robustness to data quality, acquisition protocol and preprocessing and its comparison to the state of the art is evaluated in both simulated and clinical settings. To further characterise the lesions, a subject-specific coordinate frame that divides the WM region according to the relative distance between the ventricular surface and the cortical sheet and to the lobar location is introduced. This coordinate frame is used for the comparison of lesion distributions in a population of twin pairs and for the prediction and standardisation of visual rating scales. Lastly the cross-sectional method is extended into a longitudinal framework, in which a Gaussian Mixture model built on an average image is used to constrain the representation of the individual time points. The method is validated through a purpose-build longitudinal lesion simulator and applied to the investigation of the relationship between APOE genetic status and lesion load progression.
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Dhital, Bibek. "Characterizing Brain White Matter with Diffusion-Weighted Magnetic Resonance." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-180140.
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It has been known for almost two decades that the water proton NMR signal of diffusing water molecules in brain white matter undergoes a non-monoexponential decay with increasing diffusion gradient factor b. With the help of numerical simulations and analytical expressions, much effort has been directed to describing the signal decay and to extracting relevant biophysical features of the system under investigation. However, the physical basis of such nonmonoexponential behavior is still not properly understood.
The primary difficulty in characterizing this phenomenon is the variation in behavior in the different directions of diffusion measurement. A combined framework that accounts for the diffusion process in all directions requires several parameters. Addition of many such parameters renders a model to be unwieldy and over-complicated, but over-simplifications can be shown to miss crucially relevant information in the data.
In this thesis, I have attempted to handle this problem with simple measurements that span a wide range of parameter space. Compared to often-performed measurements that probe diffusion over a time-scale of 50-100 ms with relatively low diffusion weighting, the measurements here have been done for very short diffusion times of 2 ms and also very long diffusion times up to 2 s. The temperature dependence of the diffusion coefficients has also been extensively probed. To avoid problems related to gross tissue heterogeneity, diffusion-weighted MR imaging in vivo was performed with ultra-high resolution. These simple measurements allowed sequential assessment of many possible arguments that could have led to such non-monoexponential decay curves. Finally, it was concluded that the water in the glial processes was the major contributor to the non-exponential decay, giving rise to a \'slow\' component both along the axonal fibers and transverse to them.
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Elsaeedi, Entisar Ahmed Had. "Examining the vulnerability of developing white matter to injury." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38499.
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Many neurodegenerative disorders such as Alzheimer’s disease and cerebral ischaemic stroke can be caused by excessive glutamate release. Although experimental models of cerebral ischaemia, using NMDA-R antagonists, have shown protection against acute brain damage clinical trials with such compounds have failed due to the unacceptable side-effects. Firstly, this study aimed to examine the effect of acute exposure to NMDA-R antagonists (MK-801 and memantine) on the ultrastructure features of developing and adult rat optic nerve (RON) using electron microscopy. These data showed that NMDA-R antagonists acutely damage developing white matter (WM), but not the adult WM. In addition, examination of the effect of oxygen glucose deprivation (OGD) on the ultra-structural features of P0 RONs showed a significant reduction in the viability of axons, axon density and a significant increase in glial cell injury. Secondly, this thesis has also examined whether the morphology of white matter is sexually dimorphic in both neonatal and adulthood using RON and corpus callosum. The data from this chapter observed that gender did not affect the white matter (in terms of axon diameter, density, area) at either P0 or adulthood and in addition no gender differences were seen in response to OGD-injury. However, there were some differences in the response to NMDA-R block. Specifically, gender affected axonal density following exposure to MK-801 or memantine – such gender differences were seen at both P0 and adulthood. Thirdly, this thesis investigated the expression of voltage-gated calcium channels (VGCCs) in peripheral axons. The data showed that L-type and P/Q-type channel subunits were present at low levels at P0 and increased by P10 after which they declined by P20. Both double and triple labelling (IHC) experiments demonstrated that Schwann cells express VGCCs during the myelin formation process which starts from around P10.
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Al-Griw, Mohamed A. "Molecular and cellular analysis of white matter ischaemic injury." Thesis, University of Leeds, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589408.
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White matter injury often results in clinical neurodevelopmental deficits; however, molecular mechanisms remain partially understood and there is currently no clinically effective treatment. The purpose of this study was to elucidate the molecular and cellular mechanisms underlying developmental white matter ischaemia to aid the search for therapeutic interventions. In this thesis, a particular priority was to develop an ischaemia paradigm enabling study of the extended effects of ischaemia in a controlled environment. To achieve this, I sought to use organotypic slice cultures (OSC), whereby cerebellar slices could be generated from animals where the white matter is developing and maintain it whilst exposing it to a short oxygen-glucose deprivation (OGD) insult at some defined point in the culture cycle. Using this approach, I show that culture treatment at 7 days in vitro (DIV) with OGD for twenty-minutes triggered significant injury as judged by a 58.6% reduction in cell viability 3 days post-injury. TUNEL labelling showed about 60% of cell death was apoptotic in nature. Gene expression studies using Q-RT -PCR confirmed caspase-dependent cell death. OGD also produced marked oligodendrocyte loss and myelination disturbances as seen by immunocytochemistry. Post-OGD, astrocytes and microglia became activated, and cytokine and iNOS mRNA expression was upregulated. After a transient demyelinating insult with OGD, GluR-antagonists were effective against cellular damage and myelination disturbances. Myelin gene, oligodendroglial transcription factor, and BCL-2 mRNA expression were also maintained following administration of GluR-antagonists. In addition, there seemed to be some NG2+ OPCs differentiated into MBP+ oligodendrocytes during the recovery phase as seen by proliferation- marker BrdU. Western blotting showed that a mechanism by which GluR-antagonists confer protection was independent of the CREB transcriptional activity. The results also suggest ischaemia-induced NF-kB and p38MAPK signalling pathway activation may be attributable to ionotropic GluR stimulation. The cellular damage and myelination disturbances in this ex vivo model of white matter ischaemia provides a system to study remyelination following CNS injury- induced demyelination, and may serve as a valid pre-animal test-bed for examining potential pharmacotherapies.
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Huria, Tahani Rajeb Almesmary Mohamed. "Ischaemia and neurotransmitters in mature and immature white matter." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/28523.
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Optic nerves are an appropriate and widely employed model used to study the function and the pathophysiology of central white matter. This thesis investigates ischaemic injury mechanisms in mature and immature white matter, using isolated adult and neonatal Wistar rat and balb-c mouse optic nerve. A central theme to this work is that both myelinated and nonmyelinated central white matter injury is a partially glutamate-dependent process. Electrophysiology was used to record the compound action potential (CAP) under normal and pathological conditions in both myelinated and premyelinated (post-natal day 2: P2) optic nerves. Following a period of oxygen and glucose deprivation (OGD), both white matters were susceptible to excitotoxicity; mediated by over-activation of N-methyl D-aspartate type glutamate receptors (NMDA-Rs). The previously described higher tolerance of mature mouse optic nerve to OGD was eliminated by exogenous stimulation of NMDA-Rs via direct perfusion with agonists during OGD. My data reconcile earlier contradictions in the literature regarding the significance of NMDA-Rs for ischaemic injury in white matter in the two animals. A second major finding; ischaemic injury in P2 RONs was completely prevented by the NMDARs antagonist MK-801. Interestingly, both MK-801 and a second antagonist, memantine, were toxic to P2 RONs when perfused under control conditions. The presence of NMDA-Rs on premyelinated axons was confirmed by immuno-staining. Neurotransmitters other than glutamate, such as GABA and glycine may also play a role in ischaemic injury of P2, with GABA and glycine receptor block being particularly protective of the CAP against damage. Electron-micrographs of pre-myelinated optic nerve axons and glia confirmed the data collected by electrophysiological recording of the CAP. These findings show that ischaemic damage of immature white matter is mediated largely by NMDA-Rs and that other neurotransmitter receptors also contribute to injury.
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Griffiths, John David. "White matter disconnection and neurocognitive ageing : bridging the gaps." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708490.
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Chen, Way Cherng. "Magnetic susceptibility-based white matter magnetic resonance imaging techniques." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:7272b7e6-1fb9-4a1b-a71f-2ce5dfe93fde.
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Gradient echo (GRE) imaging, a magnetic resonance imaging (MRI) technique that is sensitive to changes in the magnetic susceptibility property of tissues, has recently revealed significant signal heterogeneity in white matter (WM) at high magnetic field B0 ≥ 3T. Various aspects of the underlying white matter microstructure have been linked to the observed contrast between white matter regions. This thesis investigates the origins of the observed differences in GRE signal behaviour. We proposed an explicit multi-compartmental model of WM that incorporates realistic representation of the geometry and magnetic susceptibility of the underlying microstructure that can be used to study the effects of WM microstructural changes on GRE signal characteristics. In particular, we looked at the apparent transverse relaxation rate (R2*) and the resonance frequency, as well as their respective deviations from mono-exponential decay and linear phase evolution. Next, we investigated the effect of WM fiber orientation on GRE signal using healthy human volunteers at 3T by correlating the GRE signal from different WM regions with WM fiber orientation information. Using literature-based parameters, we demonstrated that the geometric model predicted similar trends. Lastly, we studied the effect of myelin on GRE signal using a cuprizone mouse model at 7T . An ex vivo study was used to correlate GRE signal in fixed mouse brain with normalized myelin stain intensity. Simulated GRE signal from hypothetical scenarios of demyelination were then compared with the experimental results. R2* and resonance frequency were then used in an in vivo longitudinal study to track myelin changes during demyelination and subsequent remyelination.
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Sprooten, Emma. "Genetic determinants of white matter integrity in bipolar disorder." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/6482.
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Bipolar disorder is a heritable psychiatric disorder, and several of the genes associated with bipolar disorder and related psychotic disorders are involved in the development and maintenance of white matter in the brain. Patients with bipolar disorder have an increased incidence of white matter hyper-intensities, and quantitative brain imaging studies collectively indicate subtle decreases in white matter density and integrity in bipolar patients. This suggests that genetic vulnerability to psychosis may manifest itself as reduced white matter integrity, and that white matter integrity is an endophenotype of bipolar disorder. This thesis comprises a series of studies designed to test the role of white matter in genetic risk to bipolar disorder by analysis of diffusion tensor imaging (DTI) data in the Bipolar Family Study. Various established analysis methods for DTI, including whole-brain voxel-based statistics, tract-based spatial statistics (TBSS) and probabilistic neighbourhood tractography, were applied with fractional anisotropy (FA) as the outcome measure. Widespread but subtle white matter integrity reductions were found in unaffected relatives of patients with bipolar disorder, whilst more localised reductions were associated with cyclothymic temperament. Next, the relation of white matter to four of the most prominent psychosis candidate genes, NRG1, ErbB4, DISC1 and ZNF804A, was investigated. A core haplotype in NRG1, and three of the four key single nucleotide polymorphisms (SNPs) within it, showed an association with FA in the anterior thalamic radiations and the uncinate fasciculi. For the three SNPs considered in ErbB4, results were inconclusive, but this was consistent with the background literature. Most notable however, was a clear association of a non-synonymous DISC1 SNP, Ser704Cys, with FA extending over most of the white matter in the TBSS and voxel-based analyses. Finally, FA was not associated with a genome-wide supported risk SNP in ZNF804A, a finding which could not be attributed to a lack of statistical power, and which contradicts a strong, but previously untested hypothesis. Whilst the above results need corroboration from independent studies, other studies are needed to address the cellular and molecular basis of these findings. Overall, this work provides strong support for the role of white matter integrity in genetic vulnerability to bipolar disorder and the wider psychosis spectrum and encourages its future use as an endophenotype.
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Madhavan, Kiely M. M. A. "White Matter Microstructure and Language Functioning in Healthy Aging." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1367942804.
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Sarkar, Sagari. "White matter correlates of conduct disorder and developmental psychopathy." Thesis, King's College London (University of London), 2013. http://kclpure.kcl.ac.uk/portal/en/theses/white-matter-correlates-of-conduct-disorder-and-developmental-psychopathy(9b472b3d-3557-41f1-9515-e690f6b53654).html.
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Conduct disorder (CD) is a serious disruptive behaviour disorder that is diagnosed in children who display repetitive and persistent antisocial behaviour, such as violence, robbery and vandalism. Children with CD present substantial costs to society, and are the group of children most commonly referred to mental health services. Further, CD is a strong predictor of adult Antisocial Personality Disorder and psychopathy. Research to date on the biological associates of CD has mostly compared the anatomy and function of specific brain regions in people with CD to controls. However, there is increasing recognition that brain regions do not act in isolation. Rather, they form part of integrated neural systems. Nevertheless, to date, there have been no studies on anatomical ‘connectivity’ in CD. Also there are few studies of how prenatal environment modulates the development of human limbic ‘social brain’ regions that are implicated in CD, and other abnormalities in social development. For example, prior studies reported behaviour problems in babies and children of mothers with elevated levels of stress or anxiety during pregnancy. Preliminary evidence suggests that these maternal emotional factors modulate intrauterine environment (e.g. through the stress hormone cortisol); and so may alter the development of limbic brain structures (such as the amygdala and orbitofrontal cortex) that are crucial to emotion processing and social cognition. However, to date, only one human study has examined the association between prenatal maternal mood and altered development of neural systems in children.
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Samaraweera, Amal Prasanna Rohan. "MRI white matter lesion central veins in multiple sclerosis." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/44840/.
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This thesis focuses on the use of the Magnetic Resonance Imaging (MRI) white matter lesion (WML) central vein as a biomarker for multiple sclerosis (MS). MS remains a clinical diagnosis, with reliance on MRI to support the diagnosis. Misinterpretation of the MRI can lead to misdiagnoses of diseases that mimic MS. With the increase in disease modifying treatments, accurate and timely diagnosis is needed now more than ever. Using T2* weighted imaging at 3 Tesla (T) MRI, I explored different aspects of WML central veins in patients with relapsing-remitting (RRMS), primary progressive MS (PPMS), and ischaemic small vessel disease (SVD) including: (1) the effect of using different T2* weighted sequences; (2) how T2* and susceptibility weighted imaging (SWI) and fused imaging techniques such as fluid attenuated inversion recovery (FLAIR)-SWI affected the proportion of WML central veins and; (3) determining if WML central veins were as prevalent in patients with PPMS. Further objectives included: (4) attempting to determine if vascular risk factors altered the proportion of WML central veins in patients with MS and; (5) using statistical modelling to calculate a simple diagnostic rule using WML central veins to differentiate MS from SVD. The proportion of WMLs with central veins differed significantly between patients with MS and SVD. Variations of the T2* sequence altered the proportion of WMLs with central veins, but the difference between MS and SVD remained statistically significant. T2* and SWI allowed a higher proportion of WMLs with central veins to be detected, with T2* being just as accurate as FLAIR-SWI in allowing the diagnosis of MS or SVD. Patients with PPMS and RRMS have a similarly high proportion of WMLs with central veins. High sensitivity and specificity for the diagnosis of MS versus SVD can be achieved by identifying a subset of WMLs with central veins. WML central veins could be used as an MRI biomarker using T2* imaging at 3T to differentiate cases of diagnostic uncertainty with RRMS, PPMS and SVD. Application of this imaging technique to patients with diagnostic uncertainty in prospective studies needs to be studied along with refining a clinical diagnostic rule.
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Xu, Tianyou. "Biophysical modeling of white matter in magnetic resonance imaging." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:2fa63519-5840-406d-9356-4275e4583728.
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Biophysical modeling can be combined with magnetic resonance imaging (MRI) to measure microstructural features of brain white matter (WM). Non-invasive measurements of WM microstructure is important whether we are trying to study pathology, monitor progression of disease or track drug efficacy. This DPhil project investigates the relationship between features of a biophysical model of WM and predicted/measured MRI signal properties. An explicit multi-compartment model of WM is developed in Chapter 2. This model is based on the magnetic susceptibility of myelin and captures microstructural compartments in terms of their size, shape and physical properties. We use this model to examine the role of myelin content (g-ratio and axon density) by calculating microstructure-driven field perturbations and forward predicting the gradient echo (GRE) signal. Chapter 3 focuses on myelin geometry and its relation to the GRE signal using the framework developed in Chapter 2. Current models of WM assume idealized packings of nested cylinders as axons. In reality, axons exist in varying geometries. We explore the role of geometry at the single axon and axon bundle level through simulation and by incorporating realism based on electron microscopy. We then apply this model to study demyelination (loss of healthy myelin, characteristic of many neurodegenerative diseases) by comparing simulation predictions with measurement collected from an animal model of demyelination. Overall, our results suggest that myelin geometry has a significant effect on the GRE signal and that estimates of microstructural features may be biased if myelin shape is not appropriately considered. Chapter 4 extends the models developed in Chapters 2-3 to examine WM microstructure and its relation to the balanced steady state free precession (bSSFP) signal. We focus especially on asymmetries in the bSSFP profile and explore how these attributes could provide useful biomarkers for tissue health. We fit our biophysical model of WM to bSSFP measurements to quantify features specific myelin content. Our results demonstrate promise for the extraction of clinically relevant features of WM from in vivo bSSFP data as well as challenges in the current method.
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Astolfi, Pietro. "Toward the "Deep Learning" of Brain White Matter Structures." Doctoral thesis, Università degli studi di Trento, 2022. http://hdl.handle.net/11572/337629.
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In the brain, neuronal cells located in different functional regions communicate through a dense structural network of axons known as the white matter (WM) tissue. Bundles of axons that share similar pathways characterize the WM anatomy, which can be investigated in-vivo thanks to the recent advances of magnetic resonance (MR) techniques. Diffusion MR imaging combined with tractography pipelines allows for a virtual reconstruction of the whole WM anatomy of in-vivo brains, namely the tractogram. It consists of millions of WM fibers as 3D polylines, each approximating thousands of axons. From the analysis of a tractogram, neuroanatomists can characterize well-known white matter structures and detect anatomically non-plausible fibers, which are artifacts of the tractography and often constitute a large portion of it. The accurate characterization of tractograms is pivotal for several clinical and neuroscientific applications. However, such characterization is a complex and time-consuming process that is difficult to be automatized as it requires properly encoding well-known anatomical priors. In this thesis, we propose to investigate the encoding of anatomical priors with a supervised deep learning framework. The ultimate goal is to reduce the presence of artifactual fibers to enable a more accurate automatic process of WM characterization. We devise the problem by distinguishing between volumetric and non-volumetric representations of white matter structures. In the first case, we learn the segmentation of the WM regions that represent relevant anatomical waypoints not yet classified by WM atlases. We investigate using Convolutional Neural Networks (CNNs) to exploit the volumetric representation of such priors. In the second case, the goal is to learn from the 3D polyline representation of fibers where the typical CNN models are not suitable. We introduce the novelty of using Geometric Deep Learning (GDL) models designed to process data having an irregular representation. The working assumption is that the geometrical properties of fibers are informative for the detection of tractogram artifacts. As a first contribution, we present StemSeg that extends the use of CNNs to detect the WM portion representing the waypoints of all the fibers for a specific bundle. This anatomical landmark, called stem, can be critical for extracting that bundle. We provide the results of an empirical analysis focused on the Inferior Fronto-Occipital Fasciculus (IFOF). The effective segmentation of the stem improves the final segmentation of the IFOF, outperforming with a significant gap the reference state of the art. As a second and major contribution, we present Verifyber, a supervised tractogram filtering approach based on GDL, distinguishing between anatomically plausible and non-plausible fibers. The proposed model is designed to learn anatomical features directly from the fiber represented as a 3D points sequence. The extended empirical analysis on healthy and clinical subjects reveals multiple benefits of Verifyber: high filtering accuracy, low inference time, flexibility to different plausibility definitions, and good generalization. Overall, this thesis constitutes a step toward characterizing white matter using deep learning. It provides effective ways of encoding anatomical priors and an original deep learning model designed for fiber.
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PORCU, MICHELE. "Cerebral white matter status and resting state functional MRI." Doctoral thesis, Università degli Studi di Cagliari, 2022. http://hdl.handle.net/11584/327393.
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White Matter (WM) is a pivotal component of the Central Nervous System (CNS), and its main role is the transmission of the neural impulses within the CNS and between CNS and Peripheral Nervous System (PNS). It is note from literature that changes in the WM affects the function of the CNS with effects on the higher neurological function, included cognition. Further, it has been theorized in the last decades that ageing-associated decline in higher neurological functions, in particular in the neurocognitive sphere, could be at least partly explained by the “disconnection” of the cortical areas of the brain due to the WM degeneration.
Although standard “in-vivo” imaging biomarkers of WM integrity have not been validated yet for clinical purposes, several researches have demonstrated the correlation between different potential imaging biomarkers and WM integrity.
The aim of the PhD project is to explore and better understanding the effects of WM status on the brain structure, networking and cognition. In particular, we designed three distinct explorative and cross-sectional studies; more specifically, we analyzed the effects of two Magnetic Resonance Imaging (MRI) markers of WM degeneration (the global Fractional Anisotropy (gFA) and the white matter hyperintensities burden (WMHb), respectively) on the brain activity measured with the Resting-State Functional Magnetic Resonance Imaging (rs-fMRI) technique. The project was conducted by analyzing a human population of healthy subjects extracted from the public available dataset “Leipzig Study for Mind-Body-Emotion Interactions” (LEMON). The results of these studies have been published during the PhD course on three distinct international scientific papers.
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Adib-Samii, Poneh. "Investigating the genetics of white matter hyperintensities in ischaemic stroke." Thesis, St George's, University of London, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.719147.
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White matter hyperintensities (WMH) are highly prevalent radiological findings and predictors of morbidity and mortality. Despite their importance there is limited pathophysiological understanding and therapy. WMH are influenced by genetics, environment and their interactions. This research applied genome-wide association (GWA) methods to dissect these contributions, aiming to identify novel WMH genetic risk factors. WMH GWA-studies have thus far been limited to stroke-free populations but WMH are more severe in ischaemic stroke (IS) and likely due to small vessel disease (SVD). Here >2500 IS subjects from nine GWA-studies across Europe, America and Australia were included in a collaborative study. WMH volume in the stroke-free hemisphere was quantified on MRI and adjusted for age, sex and intracranial volume. WMH variance explained by common single nucleotide polymorphisms (SNP) was doubled in hypertensives-only (45% versus 23%) and gene-byhypertension interactions accounted for a significant proportion of trait variance. WMH GWA in IS did not find significant associations. Moderately associated loci were tested for gene-by-hypertension interactions identifying three significant associations (5q23, 10q23, 12q21). Meta-analysis with WMH GWA in stroke-free populations revealed three novel associations (5q23, 2q33,14q32). The 17q25 WMH risk locus was replicated but did not associate with another manifestation of SVD, lacunar stroke. Conversely, the COL4A1 locus was associated with both WMH and lacunar stroke. Genetic risk score analyses revealed that WMH-variants contribute to Alzheimer’s Disease (AD) independent of age, but the converse was not true. The results suggest that 1) WMH genetic architecture differs between nonhypertensives and hypertensives, 2) WMH genetic risk factors overlap and are distinct from those of lacunar stroke, and 3) WMH risk factors contribute to AD rather than shared disease mechanisms. I discuss what these findings reveal about WMH pathophysiology. I conclude that environmental risk stratification may identify more homogeneous disease subgroups and gene-environment interactions, important in complex trait dissection.
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Manogaran, Praveena. "Mechanisms of white matter in multiple sclerosis and neuromyelitis optica." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/53033.
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Neuromyelitis optica (NMO) and multiple sclerosis (MS) both result in acute injury (i.e. attacks or relapses) to the central nervous system with focal demyelination and axonal loss that varies in severity along a spectrum. A variety of non-invasive structural imaging and functional tools can be used to investigate mechanisms of white matter injury and secondary axonal injury in MS and NMO. These include advanced magnetic resonance imaging (MRI) measures of myelin water fraction; optical coherence tomography (OCT) for retinal nerve fibre layer thickness and total macular volume; and transcranial magnetic stimulation (TMS) to determine cortical excitability and integrity of cortical spinal pathways.
First, the relationship between a functional measure using TMS and a structural measure of myelin in the cortico-spinal tract was examined. Structural changes were found in the descending motor output pathway white matter in NMO along with abnormal TMS measures, suggesting that there is greater spinal cord involvement and more extensive axonal loss found in NMO compared to MS.
Next, OCT was used as a measure of the anterior visual pathway and myelin water imaging of the posterior visual pathway; the effects of damage to one part of the visual system on the other was studied. Retrograde degeneration to the retina and anterograde degeneration to the optic radiations from the optic nerve was observed in both MS and NMO subjects with optic neuritis history. A correlation between the measures indicating that damage to one part may cause damage to another part of the visual pathway. Finally, damage was observed in optic pathway in MS patients without optic neuritis history suggesting that there is damage in the absence of lesions in the optic nerve.
Finally, myelin water imaging was used to investigate if the disease burden of lesions regulate the level of damage to the normal appearing white matter (NAWM) tracts. The lack of correlation between disease burden of lesions and NAWM myelin water imaging in MS suggested that damage to the NAWM was mediated by processes independent of lesions.
These techniques can be used to study and better understand demyelinating diseases such as MS and NMO.Medicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate
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Anderson, Emma S. "The Type IV Oligodendrocyte : experimental studies on chicken white matter /." Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2002/med720s.pdf.
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Scally, Brian Donal. "Commissural white matter disconnectivity in normal ageing and Alzheimer's disease." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/22351/.
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The network of commissural white matter fibres responsible for connecting the hemispheres of the brain is known as the corpus callosum (CC). Atrophy to the CC is evident in studies of aging and Alzheimer's disease (AD), but patterns and functional implications of neurodegeneration are still somewhat unclear. In this thesis, neuroimaging methods were used to further examine how structural and functional CC properties are affected by normal ageing and AD. In Study 1, diffusion tensor imaging (DTI) was used to examine the posterior CC tract bundles in young and older adults. Parietal and temporal midsagittal CC segments were particularly impaired in older adults, while occipital tracts were relatively preserved. Study 2 applied this methodology to study Mild Cognitive Impairment (MCI) and AD. MCI patients exhibited reduced integrity in midsagittal parietal segments compared to controls. AD patients exhibited reductions in parietal and temporal segments, yielding high classification accuracy (95-98%) against controls. Study 3 assessed visual interhemispheric transfer in aging using electroencephalography (EEG). Transfer speed was elongated in older adults, but was driven by earlier activation of the input hemisphere rather than delayed activation of the receiving hemisphere. This was not interpreted as impairment in older age, in line with findings of preserved occipital tracts in Study 1. Study 5 examined EEG functional connectivity methodology. We showed that connectivity was strongest at the dominant EEG frequency, which experiences slowing in older age. Previous studies using conventional frequency bands may therefore be biased against older adults. Study 6 applied these findings to study interhemispheric functional connectivity in older adults, while controlling for age-related frequency slowing. Age-related disconnectivity between frontal sites was evident, reflecting typical anterior-posterior neurodegeneration in older adults (Bennett, Madden, Vaidya, Howard, & Howard, 2010). These studies provide novel spatial and methodological insight into the CC during ageing and AD.
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Maddah, Mahnaz. "Quantitative analysis of cerebral white matter anatomy from diffusion MRI." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/45614.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 165-177).
In this thesis we develop algorithms for quantitative analysis of white matter fiber tracts from diffusion MRI. The presented methods enable us to look at the variation of a diffusion measure along a fiber tract in a single subject or a population, which allows important clinical studies toward understanding the relation between the changes in the diffusion measures and brain diseases, development, and aging. The proposed quantitative analysis is performed on a group of fiber trajectories extracted from diffusion MRI by a process called tractography. To enable the quantitative analysis we first need to cluster similar trajectories into groups that correspond to anatomical bundles and to establish the point correspondence between these variable-length trajectories. We propose a computationally-efficient approach to find the point correspondence and the distance between each trajectory to the prototype center of each bundle. Based on the computed distances we also develop a novel model-based clustering of trajectories into anatomically-known fiber bundles. In order to cluster the trajectories, we formulate an expectation maximization algorithm to infer the parameters of the gamma-mixture model that we built on the distances between trajectories and cluster centers. We also extend the proposed clustering algorithm to incorporate spatial anatomical information at different levels through hierarchical Bayesian modeling. We demonstrate the effectiveness of the proposed methods in several clinical applications. In particular, we present our findings in identifying localized group differences in fiber tracts between normal and schizophrenic populations.
by Mahnaz Maddah.
Ph.D.
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Roulois, Aude Jacqueline Alice. "Regulation of white matter oligodendrocyte progenitor cell differentiation during remyelination." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612216.
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Bei, F. "Ischaemic injury and protection of the mammalian central white matter." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/18504/.
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Ischaemic injury of the central white matter (IICWM) has been relatively little studied despite its contribution to the pathology of several neurological diseases, including stroke and vascular dementia. Research has been hampered by a lack of suitable experimental models. Here, a new model of IICWM has been developed in the rat spinal cord in vivo, and the model has been used to explore the value of agents that block voltage-gated sodium channels, or the sodium/calcium exchanger (NCX). Endothelin-1 (ET-1, a potent vasoconstrictor) was injected into the spinal cord to induce local ischaemia, and hence injury to the spinal white matter as demonstrated by blockade of axonal conduction and change of axonal morphology. The sodium channel blocking agent phenytoin was found to improve axonal conduction during the first 4.5 hours post ET-1 injection. Importantly, the protection provided by phenytoin (fosphenytoin as prodrug) persisted for at least 3 days (the longest interval studied) in animals allowed to recover from anaesthesia. The selective reverse-mode blocker of the NCX, KB-R7943 was also found to improve axonal conduction during the first 4.5 hours post ET-1 injection. Another reverse-mode blocker of the NCX, SEA0400 was also neuroprotective. Furthermore, in the longer term, KB-R7943 protected axons at 3 days post ET-1 injection. None of the study agents (phenytoin, KB-R7943 and SEA0400) diminished the severity of ET-1-induced ischaemia, revealing the effect to be a true neuroprotection, rather than an unintended diminution of the ischaemic insult. The findings are consistent with an interpretation that intracellular sodium accumulation, probably via open sodium channels, may play a role in mediating IICWM in vivo, perhaps by promoting the lethal importation of calcium ions via the reverse-mode operation of the NCX. It is concluded that partial blockade of sodium channels, or the NCX, may be effective in protecting central axons from ischaemic injury.
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Lederer, Katharina Johanna. "Relationship between white matter changes and aggression in methamphetamine dependence." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/13802.
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Background: Methamphetamine (MA) abuse is a growing problem in the world and especially in South Africa’s Western Cape. Amphetamine-type stimulants have become the second most widely abused illicit drugs worldwide. Admission data from substance abuse treatment centres in the Western Cape show the fastest increase for any drug ever noted in the country in MA related admissions. MA has neurotoxic effects on the brain leading, amongst other effects, to white matter (WM) changes. Moreover, increased levels of aggression are commonly found in individuals with MA abuse. Although behavioural deficits are well described, the underlying mechanisms are still poorly understood. While previous studies have examined WM abnormalities relating to cognitive impairment, none have investigated associations between WM integrity in individuals with MA dependence and aggression. Methods: Diffusion Tensor Imaging (DTI) was used to investigate WM changes in 40 individuals with MA dependence and 40 matched healthy control subjects. Aggression was measured with the Buss & Perry Questionnaire in 40 MA users and 36 controls. Two approaches to assess WM integrity in the brain were employed. First, whole brain voxel wise comparison across subjects using tract based spatial statistics (TBSS) in FSL was used. Fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ║) and perpendicular diffusivity (λ┴) were compared between the two groups. Second, a region of interest (ROI) approach was used, which focused on three WM tracts in the frontal brain, commonly found to play a role in aggressive behaviour: (1) the genu of the corpus callosum (CC), (2) the cingulum and (3) the uncinate fasciculus.
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Bracht, Tobias. "Characterizing white matter microstructure of the reward system in depression." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/86801/.
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This thesis demonstrates the relationship between depression symptomatology and white matter microstructure. Chapter 1 provides a systematic literature overview on white matter microstructure alterations of the reward system in depression. Findings suggest that localization and extent of white matter microstructure alterations in depression is highly dependent on the state (depression vs. remission) and the clinical subtype. Using a novel tractography algorithm, Chapter 2 provides a comprehensive instruction on how to delineate the two different branches of the MFB (supero-lateral medial forebrain bundle (slMFB) and infero-medial medial forebrain bundle (imMFB)), the main pathway of the reward system. An association between fractional anisotropy (FA), a diffusion tensor imaging (DTI)-based measure that is supposed to reflect white matter microstructure and hedonic tone, the capacity to derive pleasure from rewarding experiences is identified across a group of remitted depressed (RD) and never depressed (ND) young women. Chapter 3 uses a longitudinal design to investigate white matter microstructural changes of different pathways of the reward system from depression to remission. A distinct pattern of changes that depends on both the tract and the age is identified. Chapter 4 investigates the structural correlates of physical activity (PA). PA is reduced in depression and its benefit for depression symptomatology is well known. Using an MRI-sequence that has been shown to be specific to myelination we identify a positive correlation between PA and myelination of the right parahippocampal cingulum (PHC). This thesis contributes to the identification of structure-function associations related to the reward system in both patients with major depressive disorder (MDD) and healthy controls (HC). Results call for a careful stratification of clinically meaningful homogeneous subgroups if investigating participants with depression. Further the benefit of novel imaging methods for reconstruction of specific pathways and for a neurobiologically meaningful interpretation of the data is clearly shown.
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Fujino, Junya. "Impaired empathic abilities and reduced white matter integrity in schizophrenia." Kyoto University, 2016. http://hdl.handle.net/2433/215380.
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Mercier, Corentin. "Geometrical modeling, simplification and visualization of brain white matter tractograms." Electronic Thesis or Diss., Institut polytechnique de Paris, 2020. http://www.theses.fr/2020IPPAT048.
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Les données de tractographie (fibres) obtenues à partir d'IRM de diffusion sont difficiles d'utilisation. Dans cette thèse, nous proposons des méthodes et algorithmes pour la simplification, la visualisation et la manipulation de ces données. Nous introduisons une représentation multi-résolution des tractogrammes, plus rapides et avec une meilleure précision géométrique que les approches de simplification existantes. Nous explorons aussi diverses représentations géométriques et nous nous concentrons sur les approches de projections aux moindres carrés (MLS) par l'intermédiaire des surfaces algébriques d'ensemble de points (APSS), pour lesquelles nous réduisons la complexité, permettant l'utilisation de noyaux globaux pour l'analyse et la modélisation. Une technique de segmentation utilisant la représentation multi-résolution et permettant une meilleure reproductibilité que d'autres approches est ensuite présentée. Les tractogrammes pouvant être volumineux, nous introduisons un algorithme de compression exploitant la manière d'obtenir les données à partir des IRM de diffusion. La vitesse de cet algorithme permet même son utilisation pour la visualisation de données compressées, la décompression se faisant à la volée sur le GPU. Ces travaux de recherche et les résultats obtenus se situent à l'intersection de l'informatique graphique et de l'analyse de données médicales, ouvrant de nombreuses perspectivesTractography data (fibers) obtained from diffusion MRI present several challenges.In this thesis, we propose some useful methods and algorithms for simplification, visualization, and manipulation of these data.We introduce a new multi-resolution representation for tractograms, faster, and with higher geometric accuracy than existing simplification approaches.We also investigate various geometric representations and focus on moving least square (MLS) projection with algebraic point set surfaces (APSS), on which we reduce the complexity, allowing for the use of global kernels for analysis and modeling.A segmentation technique using the multi-resolution representation is presented, achieving better reproducibility than other approaches.Tractograms being massive, we also introduce a compression algorithm taking advantage of data obtention from diffusion MRI.The algorithm speed even allows for the direct use of compressed data for visualization, as it can be decompressed on-the-fly on the GPU.This research and the obtained results lie at the intersection between Computer Graphics and Medical Data Analysis, paving the way for numerous perspectives
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Doubal, Fergus Neil. "Do retinal microvascular abnormalities shed light on the pathophysiology of lacunar stroke?" Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5546.
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Background. Lacunar strokes account for 25% of all ischaemic stroke but the exact nature of the causative cerebral small vessel abnormality remains unknown. Pathological studies are technically difficult and brain imaging cannot adequately characterise the cerebral small vessels. The retinal blood vessels are of similar size and physiology to the cerebral small vessels and may act as a surrogate marker for these cerebral small vessels. We therefore investigated retinal microvascular abnormalities in lacunar stroke. Methods. We performed a systematic review of retinal microvascular abnormalities in lacunar stroke to clarify associations and identify where further research was required. We then established a cohort of patients presenting with lacunar stroke with cortical stroke controls to investigate differences in retinal microvascular abnormalities between stroke subtypes. All patients had MRI brain at presentation and digital retinal photography of both eyes. We investigated the prevalence of retinopathy (hard and soft exudates or haemorrhages/microaneurysms), focal arteriolar narrowing and arteriovenous nicking . We developed, validated and used novel semi-automated techniques for measuring retinal arteriolar and venular widths, retinal arteriolar geometry (branching co-efficients (change in arteriolar cross sectional area across a bifurcation) and branching angles) and fractal dimensions (reflecting branching complexity) of the vasculature. We also assessed MRI parameters in lacunar stroke. We used multivariable analysis to correct for baseline imbalances in vascular risk factors. Results. From the systematic review we demonstrated that retinal microvascular abnormalities are associated with incident and prevalent stroke but that in general, strokes were inadequately characterised and there were no data regarding retinal microvascular abnormalities in ischaemic stroke subtypes. We recruited 253 patients, 129 lacunar strokes and 124 cortical strokes, mean age 68 years. We found no difference in the prevalence of retinopathy, arteriovenous nicking, focal arteriolar narrowing or arteriolar widths between lacunar and cortical stroke subtypes. We found that venules were wider in lacunar stroke. We found no differences in arteriolar branching co-efficients or arteriolar branching angles between lacunar and cortical strokes but found that deep white matter white matter hyperintensities on MRI were associated with increased branching co-efficients and periventricular white matter hyperintensities associated with decreased branching co-efficients. We found that the fractal dimension of the vascular tree was decreased in lacunar stroke. Furthermore we found that enlarged perivascular spaces on MRI are associated with lacunar stroke and white matter disease. Conclusions. We have clearly demonstrated that retinal microvascular abnormalities differ between lacunar and cortical stroke suggesting that a distinct small vessel vasculopathy may cause lacunar stroke. We have also identified MR markers of lacunar stroke. These results suggest that venular disease (a hitherto underresearched area) may play a role in the pathophysiology of lacunar stroke. Retinal microvascular abnormalities can act as markers for cerebral small vessel disease. We plan collaborative analyses with colleagues who have performed similar studies to further assess retinal abnormalities in lacunar stroke.
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Chen, Evan I.-Wen. "Frequency shift mapping in spinal cord models of white matter demyelination." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57926.
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The behavior of MR phase and frequency in demyelination and damage in central nervous tissue white matter arises not only from traditionally associated bulk susceptibility changes, but also from changes to its tissue microstructure. A recently proposed generalized Lorentzian model of microstructure-related magnetic susceptibility effects predicts an increase in MR frequency due to damage in myelin in MS lesions. The same model also predicts reduction in MR frequency due to axonal degeneration. Here, we investigate the effect of both myelin and axonal damage through transection of white matter fibers in the dorsal column of rat cervical spinal cord. This injury generates secondary damage consisting of neurodegeneration along nerve tracts bilateral to the transection site, producing cases of Wallerian and retrograde degeneration free of excessive hemorrhage and inflammation. High-resolution frequency maps of degenerating tracts were correlated with histopathology for axons, myelin, degenerated myelin, and macrophages. Damage to myelin sheaths is prominent in Wallerian degeneration, where we observe strong correlations with increasing frequency up to 8 weeks post-injury. Retrograde degeneration, which consists predominantly of axonal damage, produces decreased frequency shift over time. The MR frequency shifts are sensitive to the effects of macrophage in filtration and debris clearance, which vary with white matter fiber density and affect rates of degeneration. We demonstrate how MR frequency can successfully characterize injury in rat spinal cord white matter in a manner consistent with predictions outlined by the Generalized Lorentzian Approximation Model, and conclude that these results suggest potential applications of MR frequency to supplement or replace current clinical techniques, such as myelin water and diffusion weighted imaging, as a non-invasive and quantitative method of assessing white matter damage in CNS.Science, Faculty of
Physics and Astronomy, Department of
Graduate
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Juma, Wafa M. "White matter lesions, C-reactive protein and microglia: A putative relation." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28338.
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White matter lesions (WML) are a clinically significant, common feature of the ageing brain associated with cognitive decline and depression. Recent research has been focused on identifying parameters which may have a correlation with WML. To this effect the acute phase protein, C-reactive protein (CRP) was shown to have an increased plasma level with progressive WML in human studies. However, due to the limitations of humam-based research the expression of CRP from brain tissue demonstrating progressive WML over a given period has not been reported. Our results have shown elevated mRNA and protein expression of CRP from rat brain tissue manifesting features of WML. Moreover, we have demonstrated that microglia, cultured from rat brain, are a source of mRNA and protein expression of CRP. We suggest that this key novel relation could be a target for future therapeutic interventions in diseases where WML and microglial activity are prominent features.
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Hu, Chengliang. "Inferring cerebral white matter fibres from diffusion tensor magnetic resonance images." Thesis, University of York, 2018. http://etheses.whiterose.ac.uk/22002/.
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The dissertation describes the research work on the inference of cerebral white matter fibres from diffusion tensor magnetic resonance images (DT-MRI), derived from the high angular resolution diffusion-weighted imaging (HARDI) data. A novel framework for inferring cerebral white matter fibres from diffusion MR images is presented. It includes feature extraction using graph based methods; feature selection with statistical pattern recognition techniques; and the inference of the white matter fibres applying machine learning methods. Four similarity measures are adopted or proposed for the fibre characterisation. Very good results are produced and a comparison is made. An evaluation of the methodology is conducted on real diffusion MRI data.
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Stamile, Claudio. "Unsupervised Models for White Matter Fiber-Bundles Analysis in Multiple Sclerosis." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1147/document.
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L’imagerie de résonance magnétique de diffusion (dMRI) est une technique très sensible pour la tractographie des fibres de substance blanche et la caractérisation de l’intégrité et de la connectivité axonale. A travers la mesure des mouvements des molécules d’eau dans les trois dimensions de l’espace, il est possible de reconstruire des cartes paramétriques reflétant l’organisation tissulaire. Parmi ces cartes, la fraction d’anisotropie (FA) et les diffusivités axiale (λa), radiale (λr) et moyenne (MD) ont été largement utilisés pour caractériser les pathologies du système nerveux central. L’emploi de ces cartes paramétriques a permis de mettre en évidence la survenue d’altérations micro structurelles de la substance blanche (SB) et de la substance grise (SG) chez les patients atteints d’une sclérose en plaques (SEP). Cependant, il reste à déterminer l’origine de ces altérations qui peuvent résulter de processus globaux comme la cascade inflammatoire et les mécanismes neurodégénératifs ou de processus plus localisés comme la démyélinisation et l’inflammation. De plus, ces processus pathologiques peuvent survenir le long de faisceaux de SB afférents ou efférents, conduisant à une dégénérescence antero- ou rétrograde. Ainsi, pour une meilleure compréhension des processus pathologiques et de leur progression dans l’espace et dans le temps, une caractérisation fine et précise des faisceaux de SB est nécessaire. En couplant l’information spatiale de la tractographie des fibres aux cartes paramétriques de diffusion, obtenues grâce à un protocole d’acquisitions longitudinal, les profils des faisceaux de SB peuvent être modélisés et analysés. Une telle analyse des faisceaux de SB peut être effectuée grâce à différentes méthodes, partiellement ou totalement non-supervisées. Dans la première partie de ce travail, nous dressons l’état de l’art des études déjà présentes dans la littérature. Cet état de l’art se focalisera sur les études montrant les effets de la SEP sur les faisceaux de SB grâce à l’emploi de l’imagerie de tenseur de diffusion. Dans la seconde partie de ce travail, nous introduisons deux nouvelles méthodes,“string-based”, l’une semi-supervisée et l’autre non-supervisée, pour extraire les faisceaux de SB. Nous montrons comment ces algorithmes permettent d’améliorer l’extraction de faisceaux spécifiques comparé aux approches déjà présentes dans la littérature. De plus, dans un second chapitre, nous montrons une extension de la méthode proposée par le couplage du formalisme “string-based” aux informations spatiales des faisceaux de SB. Dans la troisième et dernière partie de ce travail, nous décrivons trois algorithmes automatiques permettant l’analyse des changements longitudinaux le long des faisceaux de SB chez des patients atteints d’une SEP. Ces méthodes sont basées respectivement sur un modèle de mélange Gaussien, la factorisation de matrices non-négatives et la factorisation de tenseurs non-négatifs. De plus, pour valider nos méthodes, nous introduisons un nouveau modèle pour simuler des changements longitudinaux réels, base sur une fonction de probabilité Gaussienne généralisée. Des hautes performances ont été obtenues avec ces algorithmes dans la détection de changements longitudinaux d’amplitude faible le long des faisceaux de SB chez des patients atteints de SEP. En conclusion, nous avons proposé dans ce travail des nouveaux algorithmes non supervisés pour une analyse précise des faisceaux de SB, permettant une meilleure caractérisation des altérations pathologiques survenant chez les patients atteints de SEPDiffusion Magnetic Resonance Imaging (dMRI) is a meaningful technique for white matter (WM) fiber-tracking and microstructural characterization of axonal/neuronal integrity and connectivity. By measuring water molecules motion in the three directions of space, numerous parametric maps can be reconstructed. Among these, fractional anisotropy (FA), mean diffusivity (MD), and axial (λa) and radial (λr) diffusivities have extensively been used to investigate brain diseases. Overall, these findings demonstrated that WM and grey matter (GM) tissues are subjected to numerous microstructural alterations in multiple sclerosis (MS). However, it remains unclear whether these tissue alterations result from global processes, such as inflammatory cascades and/or neurodegenerative mechanisms, or local inflammatory and/or demyelinating lesions. Furthermore, these pathological events may occur along afferent or efferent WM fiber pathways, leading to antero- or retrograde degeneration. Thus, for a better understanding of MS pathological processes like its spatial and temporal progression, an accurate and sensitive characterization of WM fibers along their pathways is needed. By merging the spatial information of fiber tracking with the diffusion metrics derived obtained from longitudinal acquisitions, WM fiber-bundles could be modeled and analyzed along their profile. Such signal analysis of WM fibers can be performed by several methods providing either semi- or fully unsupervised solutions. In the first part of this work, we will give an overview of the studies already present in literature and we will focus our analysis on studies showing the interest of dMRI for WM characterization in MS. In the second part, we will introduce two new string-based methods, one semi-supervised and one unsupervised, to extract specific WM fiber-bundles. We will show how these algorithms allow to improve extraction of specific fiber-bundles compared to the approaches already present in literature. Moreover, in the second chapter, we will show an extension of the proposed method by coupling the string-based formalism with the spatial information of the fiber-tracks. In the third, and last part, we will describe, in order of complexity, three different fully automated algorithms to perform analysis of longitudinal changes visible along WM fiber-bundles in MS patients. These methods are based on Gaussian mixture model, nonnegative matrix and tensor factorisation respectively. Moreover, in order to validate our methods, we introduce a new model to simulate real longitudinal changes based on a generalised Gaussian probability density function. For those algorithms high levels of performances were obtained for the detection of small longitudinal changes along the WM fiber-bundles in MS patients. In conclusion, we propose, in this work, a new set of unsupervised algorithms to perform a sensitivity analysis of WM fiber bundle that would be useful for the characterisation of pathological alterations occurring in MS patients
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Bells, Sonya. "Multi-parametric quantification of white matter microstructure in the human brain." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/45361/.
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To date the majority of MRI studies of white matter (WM) microstructure have used diffusion tensor MRI (DT-MRI), comparing groups on a voxel-by-voxel basis. There are limitations to this approach. Firstly, the analysis approach treats each voxel independently, ignoring the fact that adjacent voxels may come from the same tract (or may come from completely separate tracts). Secondly, DT-MRI is sensitive to both interesting properties of WM (e.g., myelination, axon density), and less interesting properties (e.g., intra-voxel orientational dispersion). In contrast, other imaging approaches, based on different contrast mechanisms, can provide increased specificity and therefore sensitivity to differences in one particular attribute of tissue microstructure (e.g., myelin content or axonal density). Both quantitative magnetization transfer (qMT) imaging and multicomponent relaxometry provide proxy estimates of myelin content while the combined hindered and restricted model of diffusion (CHARMED) provides a proxy estimate of axon density. We present a novel imaging method called tractometry, which permits simultaneous quantitative assessment of these different microstructural attributes along specific pathways.Crucially, the metrics were only weakly correlated, suggesting that tractometry provides complementary WM microstructural information to DT-MRI. In developing the tractometry pipeline, we also performed a detailed examination of the qMT pipeline, identifying and reducing sources of variance to provide optimized results. We also identify a number of issues with the current state-of-the art, including the stability of tract based spatial statistics (TBSS). We show that conducting a structure-function correlation TBSS study may lead to vastly different conclusions, based simply on the participants recruited into the study. We also address microstructural asymmetry, including the degree of partial-volume effects (PVEs) from free water, which impact on WM metrics. The observed spatial heterogeneity of PVEs can potentially confound interpretation in studies where contralateral hemispheres are used as internal controls, and could either exacerbate or possibly negate tissue differences
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Ordway, Gregory A., Attila Szebeni, T. DiPeri, Craig A. Stockmeier, and Katalin Szebeni. "Shortened Telomere Length in White Matter Oligodendrocytes From Major Depressive Subjects." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etsu-works/8632.
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Freeman, Carla Patricia. "White matter correlates of neuropsychological function in young adult methamphetamine users." Master's thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/22762.
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Background: Methamphetamine (MA) abuse is a global health concern due to widespread use and harmful effects, which includes neurotoxicity. This study aimed to describe neurocognitive deficits associated with MA dependence in young adults and to explore whether these deficits correlate with white matter (WM) microstructural abnormalities using diffusion tensor imaging (DTI). Methods: Twenty-one MA dependent individuals recently enrolled in an outpatient rehabilitation program and nineteen healthy controls participated in the study. Each participant completed a neuropsychological evaluation and underwent diffusion tensor imaging within one week of testing. Average whole-brain fractional anisotropy (FA) and mean diffusion (MD) measures derived from DTI data were compared between groups. Group differences in performance within specific neurocognitive domains and in a composite global neurocognitive score (GNS) were tested using non-parametric univariate statistics and within a linear regression framework, adjusting for age and gender. Correlation analyses were conducted to test associations between the neuropsychological data and selected frontal white matter (WM) tracts, including the genu and body of the corpus callosum (CC); right and left cingulum bundle (CB); right and left uncinate fasciculus (UF); right and left anterior corona radiata (CR) and the right and left superior longitudinal fasciculus (SLF). Results: No significant between-group differences were detected for performance in any of the neuropsychological domains assessed. No relationship between FA or MD and the GNS was demonstrated in the tracts of interest. After adjusting for age and gender, significant group differences in FA and MD were detected across several regions of interest (ROI), however, these did not survive corrections for multiple comparisons. Conclusion: Cognitive performance and white matter integrity did not differ between young MA dependent subjects and healthy controls. Whatever differences that were found in white matter did not survive correction for multiple comparisons. These findings may reflect one or more of several possibilities: that brain function and structure is relatively preserved in younger individuals; or that differences were too small to be detected in this sample. Further studies should explore the effects of aging, poly-substance abuse and HIV coinfection on neurocognitive functioning and structural brain integrity in methamphetamine users.