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Register a new userDeep Learning Identifies Neuroimaging Signatures of Alzheimers Disease Using Structural and Synthesized Functional MRI Data
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Current neuroimaging techniques provide paths to investigate the structure and function of the brain in vivo and have made great advances in understanding Alzheimers disease (AD). However, the group-level analyses prevalently used for investigation and understanding of the disease are not applicable for diagnosis of individuals. More recently, deep learning, which can efficiently analyze large-scale complex patterns in 3D brain images, has helped pave the way for computer-aided individual diagnosis by providing accurate and automated disease classification. Great progress has been made in classifying AD with deep learning models developed upon increasingly available structural MRI data. The lack of scale-matched functional neuroimaging data prevents such models from being further improved by observing functional changes in pathophysiology. Here we propose a potential solution by first learning a structural-to-functional transformation in brain MRI, and further synthesizing spatially matched functional images from large-scale structural scans. We evaluated our approach by building computational models to discriminate patients with AD from healthy normal subjects and demonstrated a performance boost after combining the structural and synthesized functional brain images into the same model. Furthermore, our regional analyses identified the temporal lobe to be the most predictive structural-region and the parieto-occipital lobe to be the most predictive functional-region of our model, which are both in concordance with previous group-level neuroimaging findings. Together, we demonstrate the potential of deep learning with large-scale structural and synthesized functional MRI to impact AD classification and to identify ADs neuroimaging signatures.
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Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimers disease. While there are extensive studies on cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern across brain is missing and their interactive mechanisms with neurodegeneration are still unclear. To this end, we aim to analyze the spatiotemporal associations between ATN biomarkers using large-scale neuroimaging data. We first investigate the temporal appearances of amyloid plaques, tau tangles, and neuronal loss by modeling the longitudinal transition trajectories. Second, we propose linear mixed-effects models to quantify the pathological interactions and propagation of ATN biomarkers at each brain region. Our analysis of the current data shows that there exists a temporal latency in the build-up of amyloid to the onset of tau pathology and neurodegeneration. The propagation pattern of amyloid can be characterized by its diffusion along the topological brain network. Our models provide sufficient evidence that the progression of pathological tau and neurodegeneration share a strong regional association, which is different from amyloid.
Background:Cognitive assessments represent the most common clinical routine for the diagnosis of Alzheimers Disease (AD). Given a large number of cognitive assessment tools and time-limited office visits, it is important to determine a proper set of cognitive tests for different subjects. Most current studies create guidelines of cognitive test selection for a targeted population, but they are not customized for each individual subject. In this manuscript, we develop a machine learning paradigm enabling personalized cognitive assessments prioritization. Method: We adapt a newly developed learning-to-rank approach PLTR to implement our paradigm. This method learns the latent scoring function that pushes the most effective cognitive assessments onto the top of the prioritization list. We also extend PLTR to better separate the most effective cognitive assessments and the less effective ones. Results: Our empirical study on the ADNI data shows that the proposed paradigm outperforms the state-of-the-art baselines on identifying and prioritizing individual-specific cognitive biomarkers. We conduct experiments in cross validation and level-out validation settings. In the two settings, our paradigm significantly outperforms the best baselines with improvement as much as 22.1% and 19.7%, respectively, on prioritizing cognitive features. Conclusions: The proposed paradigm achieves superior performance on prioritizing cognitive biomarkers. The cognitive biomarkers prioritized on top have great potentials to facilitate personalized diagnosis, disease subtyping, and ultimately precision medicine in AD.
The relationship between cognition and white matter hyperintensities (WMH) volumes often depends on the accuracy of the lesion segmentation algorithm used. As such, accurate detection and quantification of WMH is of great interest. Here, we use a deep learning-based WMH segmentation algorithm, StackGen-Net, to detect and quantify WMH on 3D FLAIR volumes from ADNI. We used a subset of subjects (n=20) and obtained manual WMH segmentations by an experienced neuro-radiologist to demonstrate the accuracy of our algorithm. On a larger cohort of subjects (n=290), we observed that larger WMH volumes correlated with worse performance on executive function (P=.004), memory (P=.01), and language (P=.005).
In recent years, many papers have reported state-of-the-art performance on Alzheimers Disease classification with MRI scans from the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset using convolutional neural networks. However, we discover that when we split that data into training and testing sets at the subject level, we are not able to obtain similar performance, bringing the validity of many of the previous studies into question. Furthermore, we point out that previous works use different subsets of the ADNI data, making comparison across similar works tricky. In this study, we present the results of three splitting methods, discuss the motivations behind their validity, and report our results using all of the available subjects.
Physicians use biopsies to distinguish between different but histologically similar enteropathies. The range of syndromes and pathologies that could cause different gastrointestinal conditions makes this a difficult problem. Recently, deep learning has been used successfully in helping diagnose cancerous tissues in histopathological images. These successes motivated the research presented in this paper, which describes a deep learning approach that distinguishes between Celiac Disease (CD) and Environmental Enteropathy (EE) and normal tissue from digitized duodenal biopsies. Experimental results show accuracies of over 90% for this approach. We also look into interpreting the neural network model using Gradient-weighted Class Activation Mappings and filter activations on input images to understand the visual explanations for the decisions made by the model.
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