Hybrid High-order Functional Connectivity Networks Using Resting-state Functional MRI for Mild Cognitive Impairment Diagnosis

Conventional functional connectivity (FC), referred to as low-order FC, estimates temporal correlation of the resting-state functional magnetic resonance imaging (rs-fMRI) time series between any pair of brain regions, simply ignoring the potentially high-level relationship among these brain regions. A high-order FC based on "correlation's correlation" has emerged as a new approach for abnormality detection of brain disease. However, separate construction of the low- and high-order FC networks overlooks information exchange between the two FC levels. Such a higher-level relationship could be more important for brain diseases study. In this paper, we propose a novel framework, namely "hybrid high-order FC networks" by exploiting the higher-level dynamic interaction among brain regions for early mild cognitive impairment (eMCI) diagnosis. For each sliding window-based rs-fMRI sub-series, we construct a whole-brain associated high-order network, by estimating the correlations between the topographical information of the high-order FC sub-network from one brain region and that of the low-order FC sub-network from another brain region. With multi-kernel learning, complementary features from multiple time-varying FC networks constructed at different levels are fused for eMCI classification. Compared with other state-of-the-art methods, the proposed framework achieves superior diagnosis accuracy, and hence could be promising for understanding pathological changes of brain connectome

Deep Learning for Multiclass Classification, Predictive Modeling and Segmentation of Disease Prone Regions in Alzheimer’s Disease

One of the challenges facing accurate diagnosis and prognosis of Alzheimer’s Disease (AD) is identifying the subtle changes that define the early onset of the disease. This dissertation investigates three of the main challenges confronted when such subtle changes are to be identified in the most meaningful way. These are (1) the missing data challenge, (2) longitudinal modeling of disease progression, and (3) the segmentation and volumetric calculation of disease-prone brain areas in medical images. The scarcity of sufficient data compounded by the missing data challenge in many longitudinal samples exacerbates the problem as we seek statistical meaningfulness in multiclass classification and regression analysis. Although there are many participants in the AD Neuroimaging Initiative (ADNI) study, many of the observations have a lot of missing features which often lead to the exclusion of potentially valuable data points that could add significant meaning in many ongoing experiments. Motivated by the necessity of examining all participants, even those with missing tests or imaging modalities, multiple techniques of handling missing data in this domain have been explored. Specific attention was drawn to the Gradient Boosting (GB) algorithm which has an inherent capability of addressing missing values. Prior to applying state-of-the-art classifiers such as Support Vector Machine (SVM) and Random Forest (RF), the impact of imputing data in common datasets with numerical techniques has been also investigated and compared with the GB algorithm. Furthermore, to discriminate AD subjects from healthy control individuals, and Mild Cognitive Impairment (MCI), longitudinal multimodal heterogeneous data was modeled using recurring neural networks (RNNs). In the segmentation and volumetric calculation challenge, this dissertation places its focus on one of the most relevant disease-prone areas in many neurological and neurodegenerative diseases, the hippocampus region. Changes in hippocampus shape and volume are considered significant biomarkers for AD diagnosis and prognosis. Thus, a two-stage model based on integrating the Vision Transformer and Convolutional Neural Network (CNN) is developed to automatically locate, segment, and estimate the hippocampus volume from the brain 3D MRI. The proposed architecture was trained and tested on a dataset containing 195 brain MRIs from the 2019 Medical Segmentation Decathlon Challenge against the manually segmented regions provided therein and was deployed on 326 MRI from our own data collected through Mount Sinai Medical Center as part of the 1Florida Alzheimer Disease Research Center (ADRC)

Sparse temporally dynamic resting-state functional connectivity networks for early MCI identification

In conventional resting-state functional MRI (R-fMRI) analysis, functional connectivity is assumed to be temporally stationary, overlooking neural activities or interactions that may happen within the scan duration. Dynamic changes of neural interactions can be reflected by variations of topology and correlation strength in temporally correlated functional connectivity networks. These connectivity networks may potentially capture subtle yet short neural connectivity disruptions induced by disease pathologies. Accordingly, we are motivated to utilize disrupted temporal network properties for improving control-patient classification performance. Specifically, a sliding window approach is firstly employed to generate a sequence of overlapping R-fMRI sub-series. Based on these sub-series, sliding window correlations, which characterize the neural interactions between brain regions, are then computed to construct a series of temporal networks. Individual estimation of these temporal networks using conventional network construction approaches fails to take into consideration intrinsic temporal smoothness among successive overlapping R-fMRI subseries. To preserve temporal smoothness of R-fMRI sub-series, we suggest to jointly estimate the temporal networks by maximizing a penalized log likelihood using a fused sparse learning algorithm. This sparse learning algorithm encourages temporally correlated networks to have similar network topology and correlation strengths. We design a disease identification framework based on the estimated temporal networks, and group level network property differences and classification results demonstrate the importance of including temporally dynamic R-fMRI scan information to improve diagnosis accuracy of mild cognitive impairment patients

Multimodal Hippocampal Subfield Grading For Alzheimer’s Disease Classification

Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity measurements. The aim of our work is to improve the current classification performances based on the hippocampus with a new multimodal patch-based framework combining structural and diffusivity MRI. The combination of these two MRI modalities enables the capture of subtle structural and microstructural alterations. Moreover, we propose to study the efficiency of this new framework applied to the hippocampal subfields. To this end, we compare the classification accuracy provided by the different hippocampal subfields using volume, mean diffusivity, and our novel multimodal patch-based grading framework combining structural and diffusion MRI. The experiments conducted in this work show that our new multimodal patch-based method applied to the whole hippocampus provides the most discriminating biomarker for advanced AD detection while our new framework applied into subiculum obtains the best results for AD prediction, improving by two percentage points the accuracy compared to the whole hippocampus

Self-attention based high order sequence feature reconstruction of dynamic functional connectivity networks with rs-fMRI for brain disease classification

Dynamic functional connectivity networks (dFCN) based on rs-fMRI have demonstrated tremendous potential for brain function analysis and brain disease classification. Recently, studies have applied deep learning techniques (i.e., convolutional neural network, CNN) to dFCN classification, and achieved better performance than the traditional machine learning methods. Nevertheless, previous deep learning methods usually perform successive convolutional operations on the input dFCNs to obtain high-order brain network aggregation features, extracting them from each sliding window using a series split, which may neglect non-linear correlations among different regions and the sequentiality of information. Thus, important high-order sequence information of dFCNs, which could further improve the classification performance, is ignored in these studies. Nowadays, inspired by the great success of Transformer in natural language processing and computer vision, some latest work has also emerged on the application of Transformer for brain disease diagnosis based on rs-fMRI data. Although Transformer is capable of capturing non-linear correlations, it lacks accounting for capturing local spatial feature patterns and modelling the temporal dimension due to parallel computing, even equipped with a positional encoding technique. To address these issues, we propose a self-attention (SA) based convolutional recurrent network (SA-CRN) learning framework for brain disease classification with rs-fMRI data. The experimental results on a public dataset (i.e., ADNI) demonstrate the effectiveness of our proposed SA-CRN method

Fusing Structural and Functional Connectivities using Disentangled VAE for Detecting MCI

Brain network analysis is a useful approach to studying human brain disorders because it can distinguish patients from healthy people by detecting abnormal connections. Due to the complementary information from multiple modal neuroimages, multimodal fusion technology has a lot of potential for improving prediction performance. However, effective fusion of multimodal medical images to achieve complementarity is still a challenging problem. In this paper, a novel hierarchical structural-functional connectivity fusing (HSCF) model is proposed to construct brain structural-functional connectivity matrices and predict abnormal brain connections based on functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). Specifically, the prior knowledge is incorporated into the separators for disentangling each modality of information by the graph convolutional networks (GCN). And a disentangled cosine distance loss is devised to ensure the disentanglement's effectiveness. Moreover, the hierarchical representation fusion module is designed to effectively maximize the combination of relevant and effective features between modalities, which makes the generated structural-functional connectivity more robust and discriminative in the cognitive disease analysis. Results from a wide range of tests performed on the public Alzheimer's Disease Neuroimaging Initiative (ADNI) database show that the proposed model performs better than competing approaches in terms of classification evaluation. In general, the proposed HSCF model is a promising model for generating brain structural-functional connectivities and identifying abnormal brain connections as cognitive disease progresses.Comment: 4 figure