330 research outputs found

    Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia

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    Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome.</p

    Degenerative adversarial neuroimage nets for brain scan simulations: Application in ageing and dementia

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    Accurate and realistic simulation of high-dimensional medical images has become an important research area relevant to many AI-enabled healthcare applications. However, current state-of-the-art approaches lack the ability to produce satisfactory high-resolution and accurate subject-specific images. In this work, we present a deep learning framework, namely 4D-Degenerative Adversarial NeuroImage Net (4D-DANI-Net), to generate high-resolution, longitudinal MRI scans that mimic subject-specific neurodegeneration in ageing and dementia. 4D-DANI-Net is a modular framework based on adversarial training and a set of novel spatiotemporal, biologically-informed constraints. To ensure efficient training and overcome memory limitations affecting such high-dimensional problems, we rely on three key technological advances: i) a new 3D training consistency mechanism called Profile Weight Functions (PWFs), ii) a 3D super-resolution module and iii) a transfer learning strategy to fine-tune the system for a given individual. To evaluate our approach, we trained the framework on 9852 T1-weighted MRI scans from 876 participants in the Alzheimer's Disease Neuroimaging Initiative dataset and held out a separate test set of 1283 MRI scans from 170 participants for quantitative and qualitative assessment of the personalised time series of synthetic images. We performed three evaluations: i) image quality assessment; ii) quantifying the accuracy of regional brain volumes over and above benchmark models; and iii) quantifying visual perception of the synthetic images by medical experts. Overall, both quantitative and qualitative results show that 4D-DANI-Net produces realistic, low-artefact, personalised time series of synthetic T1 MRI that outperforms benchmark models

    Phenomenological model of diffuse global and regional atrophy using finite-element methods

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    The main goal of this work is the generation of ground-truth data for the validation of atrophy measurement techniques, commonly used in the study of neurodegenerative diseases such as dementia. Several techniques have been used to measure atrophy in cross-sectional and longitudinal studies, but it is extremely difficult to compare their performance since they have been applied to different patient populations. Furthermore, assessment of performance based on phantom measurements or simple scaled images overestimates these techniques' ability to capture the complexity of neurodegeneration of the human brain. We propose a method for atrophy simulation in structural magnetic resonance (MR) images based on finite-element methods. The method produces cohorts of brain images with known change that is physically and clinically plausible, providing data for objective evaluation of atrophy measurement techniques. Atrophy is simulated in different tissue compartments or in different neuroanatomical structures with a phenomenological model. This model of diffuse global and regional atrophy is based on volumetric measurements such as the brain or the hippocampus, from patients with known disease and guided by clinical knowledge of the relative pathological involvement of regions and tissues. The consequent biomechanical readjustment of structures is modelled using conventional physics-based techniques based on biomechanical tissue properties and simulating plausible tissue deformations with finite-element methods. A thermoelastic model of tissue deformation is employed, controlling the rate of progression of atrophy by means of a set of thermal coefficients, each one corresponding to a different type of tissue. Tissue characterization is performed by means of the meshing of a labelled brain atlas, creating a reference volumetric mesh that will be introduced to a finite-element solver to create the simulated deformations. Preliminary work on the simulation of acquisition artefa- - cts is also presented. Cross-sectional and

    Validation of Diffusion Kurtosis Imaging as an Early-Stage Biomarker of Parkinson's Disease in Animal Models

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    Diffusion kurtosis imaging (DKI), which is a mathematical extension of diffusion tensor imaging (DTI), assesses non-Gaussian water diffusion in the brain. DKI proved to be effective in supporting the diagnosis of different neurodegenerative disorders. Its sensitively detects microstructural changes in the brain induced by either protein accumulation, glial cell activation or neurodegeneration as observed in mouse models of Parkinson's disease. We applied two experimental models of Parkinson's disease to validate the diagnostic utility of DKI in early and late stage of disease pathology. We present two DKI analysis methods: (1) tract based spatial statistics (TBSS), which is a hypothesis independent data driven approach intended to evaluate white matter changes; and (2) region of interest (ROI) based analysis based on hypothesis of ROIs relevant for Parkinson's disease, which is specifically used for gray matter changes. The main aim of this chapter is to provide detailed information of how to perform the DKI imaging acquisition and analysis in the mouse brain, which can be, to some extent translated to humans
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