Learning Brain Connectivity Sub-networks by Group- Constrained Sparse Inverse Covariance Estimation for Alzheimer's Disease Classification

Background/Aims: Brain functional connectivity networks constructed from resting-state functional magnetic resonance imaging (rs-fMRI) have been widely used for classifying Alzheimer's disease (AD) from normal controls (NC). However, conventional correlation analysis methods only capture the pairwise information, which may not be capable of revealing an adequate and accurate functional connectivity relationship among brain regions in the whole brain. Additionally, the non-sparse connectivity networks commonly contain a large number of spurious or insignificant connections, which are inconsistent with the sparse connectivity of actual brain networks in nature and may deteriorate the classification performance of Alzheimer's disease.Methods: To address these problems, in this paper, a new classification framework is proposed by combining the Group-constrained topology structure detection with sparse inverse covariance estimation (SICE) method to build the functional brain sub-network for each brain region. Particularly, to tune the sensitive analysis of the regularized parameters in the SICE method, a nested leave-one-out cross-validation (LOOCV) method is adopted. Sparse functional connectivity networks are thus effectively constructed by using the optimal regularized parameters. Finally, a decision classification tree (DCT) classifier is trained for classifying AD from NC based on these optimal functional brain sub-networks. The convergence performance of our proposed method is furthermore evaluated by the trend of coefficient variation.Results: Experiment results indicate that a LOOCV classification accuracy of 81.82% with a sensitivity of 80.00%, and a specificity of 83.33% can be obtained by using the proposed method for the classification AD from NC, and outperforms the most state-of-the-art methods in terms of the classification accuracy. Additionally, the experiment results of the convergence performance further suggest that our proposed scheme has a high rate of convergence. Particularly, the abnormal brain regions and functional connections identified by our proposed framework are highly associated with the underpinning pathological mechanism of the AD, which are consistent with previous studies.Conclusion: These results have demonstrated the effectiveness of the proposed Group- constrained SICE method, and are capable of clinical value to the diagnosis of Alzheimer's disease

Functional brain network classification with compact representation of SICE matrices

Recently, sparse inverse covariance estimation (SICE) technique has been employed to model functional brain connectivity. The inverse covariance matrix (SICE matrix in short) estimated for each subject is used as a representation of brain connectivity to discriminate Alzheimers disease from normal controls. However, we observed that direct use of the SICE matrix does not necessarily give satisfying discrimination, due to its high dimensionality and the scarcity of training subjects. Looking into this problem, we argue that the intrinsic dimensionality of these SICE matrices shall be much lower, considering i) an SICE matrix resides on a Riemannian manifold of symmetric positive definiteness (SPD) matrices, and ii) human brains share common patterns of connectivity across subjects. Therefore, we propose to employ manifold-based similarity measures and kernel-based PCA to extract principal connectivity components as a compact representation of brain network. Moreover, to cater for the requirement of both discrimination and interpretation in neuroimage analysis, we develop a novel pre-image estimation algorithm to make the obtained connectivity components anatomically interpretable. To verify the efficacy of our method and gain insights into SICE based brain networks, we conduct extensive experimental study on synthetic data and real rs-fMRI data from the ADNI data set. Our method outperforms the comparable methods and improves the classification accuracy significantly

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. DISCUSSION: Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial desig