Splenium tract projections of the corpus callosum to the parietal cortex classifies Alzheimer’s disease and mild cognitive impairment

The corpus callosum (CC) is the largest bundle of white matter tracts in the brain connecting the left and right cerebral hemispheres. The posterior region of the CC, known as the splenium, seems to be relatively preserved throughout the lifespan and is regularly examined for indications of various pathologies, including Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). However, the splenium has rarely been investigated in terms of its distinct inter-hemispheric tract bundles that project to bilateral occipital, parietal and temporal areas of the cortex. The aim of the present study was to determine if any of these sub-splenium tract bundles are specifically affected by individuals with AD and MCI compared to normal controls. Diffusion Tensor Imaging was used to directly examine the integrity of these distinct tract bundles and their diffusion metrics were compared between groups of MCI, AD, and control individuals. Results revealed that differences between MCI, AD, and controls were particularly evident at parietal tracts of the CC splenium and were consistent with an interpretation of compromised white matter integrity. Combined parietal tract diffusivity and density information strongly discriminated between AD patients and controls with an accuracy (AUC) of 97.19%. Combined parietal tract diffusivity parameters correctly classified MCI subjects against controls with an accuracy of 74.97%. These findings demonstrated the potential of examining the CC splenium in terms of its distinct inter-hemispheric tract bundles for the diagnosis of AD and MCI

Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction

BACKGROUND: Intrauterine growth restriction is associated with short-and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction.OBJECTIVES: In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment.METHODS: We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age.RESULTS: Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 +/- 0.018 vs 0.315 +/- 0.015; P =.010; motor, 0.322 +/- 0.019 vs 0.319 +/- 0.020; P =.019) and integrity cortico-striatal-thalamic (0.407 +/- 0.040 vs 0.399 +/- 0.034; P =.018; motor, 0.417 +/- 0.044 vs 0.409 +/- 0.046; P =.016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877).CONCLUSIONS: These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases

Quantitative magnetization transfer of white matter tracts correlates with diffusion tensor imaging indices in predicting the conversion from mild cognitive impairment to Alzheimer's disease

Patients with amnestic mild cognitive impairment (aMCI) have higher probability to develop Alzheimer's disease (AD) than elderly controls. The detection of subtle changes in brain structure associated with disease progression and the development of tools to identify patients at high risk for dementia in a short time is crucial. Here, we used probabilistic white matter (WM) tractography to explore microstructural alterations within the main association, limbic, and commissural pathways in aMCI patients who converted to AD after 1 year follow-up (MCIconverters) and those who remained stable (MCIstable). Both diffusion tensor imaging (DTI) and quantitative magnetization transfer (qMT) parameters have been considered for a comprehensive pathophysiological characterization of the WM damage. Overall, tract-specific parameters derived from qMT and DTI at baseline were able to differentiate aMCI patients who converted to AD from those who remained stable in time. In particular, the qMT exchange rate, RMB0, of the right uncinate fasciculus was significantly decreased in MCIconverters, whereas fractional anisotropy was significantly decreased in the bilateral superior cingulum in MCIconverters compared to MCIstable. These results confirm the involvement of WM and particularly of association fibers in the progression of AD, highlighting disconnection as a potential mechanism

Gradient echo-based quantitative MRI of human brain at 7T : Mapping of T1, MT saturation and local flip angle

Quantitative MRI (qMRI) refers to the process of deriving maps of MR contrast parameters, such as relaxation times, from conventional images. If the qMRI maps have a high degree of precision and a low degree of bias, they can be compared longitudinally, across subjects, and (ideally) between measurement protocols and research sites. They also provide a more direct biophysical interpretation of the pixel intensities. The increased magnetization of spins at ultra-high field (UHF) strengths of 7T and above could potentially be translated into higher spatial resolution and/or reduced scan time. This thesis tackles UHF-related challenges in qMRI, namely the increased inhomogeneity of the radio frequency (RF) field (B1) and increased specific absorption rate (SAR). The changing relaxation times (i.e. prolonged T1 and shortened T2) also needs to be accounted for.Here, spoiled gradient-recalled echo (GRE) techniques are employed to map (primarily) two structural MR parameters, i.e. the longitudinal relaxation time (T1) and the magnetization transfer (MT) saturation (MTsat). Because of its influence at UHF, emphasis is also put on mapping of the local flip angle. Primarily, qMRI is performed by the inversion of analytical signal equations, as opposed to numerical approaches.The process of implementing and modifying the dual flip angle (DFA) technique in conjunction with an MT-weighted GRE for 7T is described. Implementation is performed within the well-established multi-parameter mapping (MPM) framework and special attention is afforded to the reduction of biases as well as overcoming saftey restrictions imposed by SAR. An approach to obtain high-SNR low-bias flip angle maps at 7T, using the dual refocusing echo acquisition mode (DREAM) technique is also presented. This is important since high fidelity flip angle maps are a prerequisite in DFA-based T1-mapping and recommended for correcting MTsat at UHF. Furthermore, MPRAGE-based techniques are discussed. Firstly, it is demonstrated how to most effectively obtain B1-corrected MPRAGE images of “pure” T1 contrast using a sequential protocol This is followed by a description of T1-mapping using MP2RAGE. Finally, an innovative technique for simultaneous mapping of T1 and the local flip angle is introduced, dubbed “MP3RAGE”

Development and application of novel algorithms for quantitative analysis of magnetic resonance imaging in multiple sclerosis.

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Cervical weakness and preterm birth: The structure and function of the internal cervical os

The cervix is integral to the maintenance of pregnancy and timely delivery of the baby. Mechanical failure of the cervix resulting in spontaneous preterm birth presents with collapse of the internal os, yet little is known about why the cervix behaves in this way. This may in part be due to research being technically limited and/or limited to punch biopsies of the distal cervix that did not include tissue from the internal os. The aim of this thesis was to re-evaluate cervical anatomy using novel laboratory and imaging methods to gain further insight into the structure of the cervix and how this may influence function during pregnancy. To achieve this, whole cervical samples were obtained from women undergoing hysterectomy for benign pathology. Uterine tissue was subsequently fixed and analysed using 2D and 3D histological methods. Cervical anatomy was characterised using markers for smooth muscle and collagen and analysed using computer-assisted quantification methods. Sequential tissue slices were then reconstructed to produce 3D models of the proximal, middle and distal cervix. High-resolution diffusion-tensor imaging was used to determine whether complex cervical anatomy could be visualised using radiological methods. Tissue was assessed using quantitative and qualitative diffusion methods, and directly compared to immunohistochemically stained tissue. The results obtained demonstrated that diffusion-tensor imaging accurately assessed cervical anatomy and provided further detail in terms of fibre volume, density and organisation. Ex vivo endoscopic ultrasound was used to assess whether current, established medical imaging technology could discern cervical smooth muscle and collagen fibres. Although this method could be used to identify gross anatomical structures, it was not an appropriate method to identify cervical microanatomy. The results described in this thesis provide further insight into how the cervix resists intrauterine forces throughout pregnancy, and then dilates and effaces to allow for delivery of a fetus. Diffusion-tensor imaging accurately assessed cervical anatomy, which may have implications for in vivo characterisation of cervical remodelling during pregnancy and identifying those at risk of delivering early. Finally, observations in this thesis encourage continued re-examination of the cervix using high-resolution imaging to provide insight into function and to develop strategies to discern cervical insufficiency from other known causes of preterm birth