31 research outputs found

    Supplemental material for Increasing cerebral blood flow improves cognition into late stages in Alzheimer’s disease mice

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    Supplemental Material for Increasing cerebral blood flow improves cognition into late stages in Alzheimer’s disease mice by Oliver Bracko, Brendah N Njiru, Madisen Swallow, Muhammad Ali, Mohammad Haft-Javaherian and Chris B Schaffer in Journal of Cerebral Blood Flow & Metabolism</p

    Data from: Deep convolutional neural networks for segmenting 3D in vivo multiphoton images of vasculature in Alzheimer disease mouse models

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    The health and function of tissue rely on its vasculature network to provide reliable blood perfusion. Volumetric imaging approaches, such as multiphoton microscopy, are able to generate detailed 3D images of blood vessels that could contribute to our understanding of the role of vascular structure in normal physiology and in disease mechanisms. The segmentation of vessels, a core image analysis problem, is a bottleneck that has prevented the systematic comparison of 3D vascular architecture across experimental populations. We explored the use of convolutional neural networks to segment 3D vessels within volumetric in vivo images acquired by multiphoton microscopy. We evaluated different network architectures and machine learning techniques in the context of this segmentation problem. We show that our optimized convolutional neural network architecture, which we call DeepVess, yielded a segmentation accuracy that was better than both the current state-of-the-art and a trained human annotator, while also being orders of magnitude faster. To explore the effects of aging and Alzheimer's disease on capillaries, we applied DeepVess to 3D images of cortical blood vessels in young and old mouse models of Alzheimer's disease and wild type littermates. We found little difference in the distribution of capillary diameter or tortuosity between these groups, but did note a decrease in the number of longer capillary segments (>75μm) in aged animals as compared to young, in both wild type and Alzheimer's disease mouse models. These data support these findings.This work was supported by the European Research Council grant 615102 (NN), the National Institutes of Health grant AG049952 (CS), the National Institutes of Health grants R01LM012719 and R01AG053949 (MS), and the National Science Foundation Cornell NeuroNex Hub grant (1707312, MS and CS)

    Virtual Microstructure Generation of Asphaltic Mixtures

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    This thesis describes the development and application of a virtual microstructure generator incorporated with post-processing image analysis methods that can be used to fabricate a virtual, two-dimensional microstructure of asphaltic mixtures. In the generator, geometrical characteristics such as aggregate gradation, aggregate area fraction, angularity, orientation, and elongation were used to transform data from a three-dimensional (3D) mixture into its two-dimensional (2D) microstructure. The 2D virtual microstructures were generated from real 3D mixture information of asphaltic composites. Resulting virtual microstructures were then compared to real cross-sectional microstructure images obtained from actual samples for validation. Comparison presented a good agreement between the virtual and real microstructures, which demonstrates that the new 3D-2D transformation algorithms were properly developed and implemented into the virtual microstructure generator. Although much future work is required, the current development is at least sufficient to demonstrate the benefits and potential of this effort. Virtual fabrication and testing can result in significant time and cost savings compared to more expensive and repetitive laboratory fabrication and performance tests of actual specimens. Adviser: Yong-Rak Ki

    QUANTITATIVE ASSESSMENT OF CEREBRAL MICROVASCULATURE USING MACHINE LEARNING AND NETWORK ANALYSIS

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    Vasculature networks are responsible for providing reliable blood perfusion to tissues in health or disease conditions. Volumetric imaging approaches, such as multiphoton microscopy, can generate detailed 3D images of blood vessel networks allowing researchers to investigate different aspects of vascular structures and networks in normal physiology and disease mechanisms. Image processing tasks such as vessel segmentation and centerline extraction impede research progress and have prevented the systematic comparison of 3D vascular architecture across large experimental populations in an objective fashion. The work presented in this dissertation provides complete a fully-automated, open-source, and fast image processing pipeline that is transferable to other research areas and practices with minimal interventions and fine-tuning. As a proof of concept, the applications of the proposed pipeline are presented in the contexts of different biomedical and biological research questions ranging from the stalling capillary phenomenon in Alzheimer’s disease to the drought resistance of xylem networks in various tree species and wood types

    A topological encoding convolutional neural network for segmentation of 3D multiphoton images of brain vasculature using persistent homology

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    The clinical evidence suggests that cognitive disorders are associated with vasculature dysfunction and decreased blood flow in the brain. Hence, a functional understanding of the linkage between brain functionality and the vascular network is essential. However, methods to systematically and quantitatively describe and compare structures as complex as brain blood vessels are lacking. 3D imaging modalities such as multiphoton microscopy enables researchers to capture the network of brain vasculature with high spatial resolutions. Nonetheless, image processing and inference are some of the bottlenecks for biomedical research involving imaging, and any advancement in this area impacts many research groups. Here, we propose a topological encoding convolutional neural network based on persistent homology to segment 3D multiphoton images of brain vasculature. We demonstrate that our model outperforms state-of-the-art models in terms of the Dice coefficient and it is comparable in terms of other metrics such as sensitivity. Additionally, the topological characteristics of our model's segmentation results mimic manual ground truth. Our code and model are open source at https://github.com/mhaft/DeepVess.National Institute of Biomedical Imaging and Bioengineering (Grant P41EB-015903)National Institutes of Health (U.S.) (Grant P41EB015902

    Data from: A pilot study investigating the effects of voluntary exercise on capillary stalling and cerebral blood flow in the APP/PS1 mouse model of Alzheimer’s disease

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    Additional authors are listed at: https://humancomputation.org/sc-running/Exercise exerts a beneficial effect on the major pathological and clinical symptoms associated with Alzheimer’s disease in humans and mouse models of the disease. While numerous mechanisms for such benefits from exercise have been proposed, a clear understanding of the causal links remains elusive. Recent studies also suggest that cerebral blood flow in the brain of both Alzheimer’s patients and mouse models of the disease is decreased and that the cognitive symptoms can be improved when blood flow is restored. We therefore hypothesized that the mitigating effect of exercise on the development and progression of Alzheimer’s disease may be mediated through an increase in the otherwise reduced brain blood flow. To test this idea, we examined the impact of three months of voluntary wheel running in ~1 year old APP/PS1 mice on short-term memory function, brain inflammation, amyloid deposition, and cerebral blood flow. Our findings that exercise led to improved memory function, a trend toward reduced brain inflammation, markedly increased neurogenesis in the dentate gyrus, and no changes in amyloid-beta deposits are consistent with other reports on the impact of exercise on the progression of Alzheimer’s related symptoms in mouse models. Notably, we did not observe any impact of wheel running on overall cortical blood flow nor on the incidence of non-flowing capillaries, the mechanism we recently identified as the cause of cerebral blood flow deficits in mouse models of Alzheimer’s disease. We did, however, note that running mice had, on average, slightly larger diameter capillaries in the cortex. Overall, our results replicate previous findings that exercise is able to ameliorate certain aspects of Alzheimer’s disease pathology, but show that this benefit does not appear to act though increases in cerebral blood flow. The dataset supports the findings of this study.DFG German Research Foundation, National Science Foundation Graduate Research Fellowship, the German National Academic Scholarship Foundation, Affinito-Stewart Grant of the President’s Council of Cornell Women, the National Institutes of Health grants AG049952 and NS108472, and the BrightFocus Foundation

    Segmentation of anatomical layers and imaging artifacts in intravascular polarization sensitive optical coherence tomography using attending physician and boundary cardinality losses

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    Intravascular ultrasound and optical coherence tomography are widely available for assessing coronary stenoses and provide critical information to optimize percutaneous coronary intervention. Intravascular polarization-sensitive optical coherence tomography (PS-OCT) measures the polarization state of the light scattered by the vessel wall in addition to conventional cross-sectional images of subsurface microstructure. This affords reconstruction of tissue polarization properties and reveals improved contrast between the layers of the vessel wall along with insight into collagen and smooth muscle content. Here, we propose a convolutional neural network model, optimized using two new loss terms (Boundary Cardinality and Attending Physician), that takes advantage of the additional polarization contrast and classifies the lumen, intima, and media layers in addition to guidewire and plaque shadows. Our model segments the media boundaries through fibrotic plaques and continues to estimate the outer media boundary behind shadows of lipid-rich plaques. We demonstrate that our multi-class classification model outperforms existing methods that exclusively use conventional OCT data, predominantly segment the lumen, and consider subsurface layers at most in regions of minimal disease. Segmentation of all anatomical layers throughout diseased vessels may facilitate stent sizing and will enable automated characterization of plaque polarization properties for investigation of the natural history and significance of coronary atheromas.</p

    Deep convolutional neural networks for segmenting 3D <i>in vivo</i> multiphoton images of vasculature in Alzheimer disease mouse models

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    The health and function of tissue rely on its vasculature network to provide reliable blood perfusion. Volumetric imaging approaches, such as multiphoton microscopy, are able to generate detailed 3D images of blood vessels that could contribute to our understanding of the role of vascular structure in normal physiology and in disease mechanisms. The segmentation of vessels, a core image analysis problem, is a bottleneck that has prevented the systematic comparison of 3D vascular architecture across experimental populations. We explored the use of convolutional neural networks to segment 3D vessels within volumetric in vivo images acquired by multiphoton microscopy. We evaluated different network architectures and machine learning techniques in the context of this segmentation problem. We show that our optimized convolutional neural network architecture with a customized loss function, which we call DeepVess, yielded a segmentation accuracy that was better than state-of-the-art methods, while also being orders of magnitude faster than the manual annotation. To explore the effects of aging and Alzheimer’s disease on capillaries, we applied DeepVess to 3D images of cortical blood vessels in young and old mouse models of Alzheimer’s disease and wild type littermates. We found little difference in the distribution of capillary diameter or tortuosity between these groups, but did note a decrease in the number of longer capillary segments (>75μm) in aged animals as compared to young, in both wild type and Alzheimer’s disease mouse models.</div
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