Multi-modal Neuroimaging Feature Selection with Consistent Metric Constraint for Diagnosis of Alzheimer’s Disease

The accurate diagnosis of Alzheimer's disease (AD) and its early stage, e.g., mild cognitive impairment (MCI), is essential for timely treatment or possible intervention to slow down AD progression. Recent studies have demonstrated that multiple neuroimaging and biological measures contain complementary information for diagnosis and prognosis. Therefore, information fusion strategies with multi-modal neuroimaging data, such as voxel-based measures extracted from structural MRI (VBM-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), have shown their effectiveness for AD diagnosis. However, most existing methods are proposed to simply integrate the multi-modal data, but do not make full use of structure information across the different modalities. In this paper, we propose a novel multi-modal neuroimaging feature selection method with consistent metric constraint (MFCC) for AD analysis. First, the similarity is calculated for each modality (i.e. VBM-MRI or FDG-PET) individually by random forest strategy, which can extract pairwise similarity measures for multiple modalities. Then the group sparsity regularization term and the sample similarity constraint regularization term are used to constrain the objective function to conduct feature selection from multiple modalities. Finally, the multi-kernel support vector machine (MK-SVM) is used to fuse the features selected from different models for final classification. The experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) show that the proposed method has better classification performance than the start-of-the-art multimodality-based methods. Specifically, we achieved higher accuracy and area under the curve (AUC) for AD versus normal controls (NC), MCI versus NC, and MCI converters (MCI-C) versus MCI non-converters (MCI-NC) on ADNI datasets. Therefore, the proposed model not only outperforms the traditional method in terms of AD/MCI classification, but also discovers the characteristics associated with the disease, demonstrating its promise for improving disease-related mechanistic understanding

Identifying Multimodal Intermediate Phenotypes between Genetic Risk Factors and Disease Status in Alzheimer’s Disease

Neuroimaging genetics has attracted growing attention and interest, which is thought to be a powerful strategy to examine the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on structures or functions of human brain. In recent studies, univariate or multivariate regression analysis methods are typically used to capture the effective associations between genetic variants and quantitative traits (QTs) such as brain imaging phenotypes. The identified imaging QTs, although associated with certain genetic markers, may not be all disease specific. A useful, but underexplored, scenario could be to discover only those QTs associated with both genetic markers and disease status for revealing the chain from genotype to phenotype to symptom. In addition, multimodal brain imaging phenotypes are extracted from different perspectives and imaging markers consistently showing up in multimodalities may provide more insights for mechanistic understanding of diseases (i.e., Alzheimer’s disease (AD)). In this work, we propose a general framework to exploit multi-modal brain imaging phenotypes as intermediate traits that bridge genetic risk factors and multi-class disease status. We applied our proposed method to explore the relation between the well-known AD risk SNP APOE rs429358 and three baseline brain imaging modalities (i.e., structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and F-18 florbetapir PET scans amyloid imaging (AV45)) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The empirical results demonstrate that our proposed method not only helps improve the performances of imaging genetic associations, but also discovers robust and consistent regions of interests (ROIs) across multi-modalities to guide the disease-induced interpretation

The Characterization of Alzheimer’s Disease and the Development of Early Detection Paradigms: Insights from Nosology, Biomarkers and Machine Learning

Alzheimer’s Disease (AD) is the only condition in the top ten leading causes of death for which we do not have an effective treatment that prevents, slows, or stops its progression. Our ability to design useful interventions relies on (a) increasing our understanding of the pathological process of AD and (b) improving our ability for its early detection. These goals are impeded by our current reliance on the clinical symptoms of AD for its diagnosis. This characterizations of AD often falsely assumes a unified, underlying AD-specific pathology for similar presentations of dementia that leads to inconsistent diagnoses. It also hinges on postmortem verification, and so is not a helpful method for identifying patients and research subjects in the beginning phases of the pathophysiological process. Instead, a new biomarker-based approach provides a more biological understanding of the disease and can detect pathological changes up to 20 years before the clinical symptoms emerge. Subjects are assigned a profile according to their biomarker measures of amyloidosis (A), tauopathy (T) and neurodegeneration (N) that reflects their underlying pathology in vivo. AD is confirmed as the underlying pathology when subjects have abnormal values of both amyloid and tauopathy biomarkers, and so have a biomarker profile of A+T+(N)- or A+T+(N)+. This new biomarker based characterization of AD can be combined with machine learning techniques in multimodal classification studies to shed light on the elements of the AD pathological process and develop early detection paradigms. A guiding research framework is proposed for the development of reliable, biologically-valid and interpretable multimodal classification models

Enhancing Alzheimer Disease Segmentation through Adaptively Regularized Weighted Kernel-Based Clustering

Image segmentation is important in image analysis because it helps to locate objects and boundaries within a picture. This study offers Adaptively Regularized Weighted Kernel-Based Clustering (ARWKC), a unique segmentation technique built exclusively for recovering brain tissue from medical pictures. The proposed approach incorporates adaptive regularization and weighted kernel-based clustering techniques to increase the accuracy and resilience of brain tissue segmentation. The picture is initially preprocessed with the ARWKC method to improve its quality and eliminate any noise or artifacts. The adaptive regularization method is then utilized to effectively deal with the visual variation of brain tissue in clinical images. This adaptive regularization contributes to more accurate and consistent segmentation outcomes. The weighted kernel-based clustering method is then used to find and group pixels with comparable properties, with a focus on brain tissue areas. This clustering approach employs a weighted kernel function that takes into account both geographical closeness and pixel intensities, allowing the algorithm to capture local picture features and improve segmentation accuracy. Extensive experiments were conducted on a collection of medical images to evaluate the efficacy of the ARWKC algorithm. The well-known k-means clustering method, often used in image segmentation applications, was utilized as a benchmark for comparison. In terms of accuracy and resilience for brain tissue segmentation, the experimental findings showed that the ARWKC method surpasses the k-means clustering approach

Automated detection of Alzheimer disease using MRI images and deep neural networks- A review

Early detection of Alzheimer disease is crucial for deploying interventions and slowing the disease progression. A lot of machine learning and deep learning algorithms have been explored in the past decade with the aim of building an automated detection for Alzheimer. Advancements in data augmentation techniques and advanced deep learning architectures have opened up new frontiers in this field, and research is moving at a rapid speed. Hence, the purpose of this survey is to provide an overview of recent research on deep learning models for Alzheimer disease diagnosis. In addition to categorizing the numerous data sources, neural network architectures, and commonly used assessment measures, we also classify implementation and reproducibility. Our objective is to assist interested researchers in keeping up with the newest developments and in reproducing earlier investigations as benchmarks. In addition, we also indicate future research directions for this topic.Comment: 22 Pages, 5 Figures, 7 Table

Early identification of mild cognitive impairment using incomplete random forest-robust support vector machine and FDG-PET imaging

Alzheimer’s disease (AD) is the most common type of dementia and will be an increasing health problem in society as the population ages. Mild cognitive impairment (MCI) is considered to be a prodromal stage of AD. The ability to identify subjects with MCI will be increasingly important as disease modifying therapies for AD are developed. We propose a semi-supervised learning method based on robust optimization for the identification of MCI from [18F]Fluorodeoxyglucose PET scans. We extracted three groups of spatial features from the cortical and subcortical regions of each FDG-PET image volume. We measured the statistical uncertainty related to these spatial features via transformation using an incomplete random forest and formulated the MCI identification problem under a robust optimization framework. We compared our approach to other state-of-the-art methods in different learning schemas. Our method outperformed the other techniques in the ability to separate MCI from normal controls

Machine Learning for Multiclass Classification and Prediction of Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) is an irreversible neurodegenerative disorder and a common form of dementia. This research aims to develop machine learning algorithms that diagnose and predict the progression of AD from multimodal heterogonous biomarkers with a focus placed on the early diagnosis. To meet this goal, several machine learning-based methods with their unique characteristics for feature extraction and automated classification, prediction, and visualization have been developed to discern subtle progression trends and predict the trajectory of disease progression. The methodology envisioned aims to enhance both the multiclass classification accuracy and prediction outcomes by effectively modeling the interplay between the multimodal biomarkers, handle the missing data challenge, and adequately extract all the relevant features that will be fed into the machine learning framework, all in order to understand the subtle changes that happen in the different stages of the disease. This research will also investigate the notion of multitasking to discover how the two processes of multiclass classification and prediction relate to one another in terms of the features they share and whether they could learn from one another for optimizing multiclass classification and prediction accuracy. This research work also delves into predicting cognitive scores of specific tests over time, using multimodal longitudinal data. The intent is to augment our prospects for analyzing the interplay between the different multimodal features used in the input space to the predicted cognitive scores. Moreover, the power of modality fusion, kernelization, and tensorization have also been investigated to efficiently extract important features hidden in the lower-dimensional feature space without being distracted by those deemed as irrelevant. With the adage that a picture is worth a thousand words, this dissertation introduces a unique color-coded visualization system with a fully integrated machine learning model for the enhanced diagnosis and prognosis of Alzheimer\u27s disease. The incentive here is to show that through visualization, the challenges imposed by both the variability and interrelatedness of the multimodal features could be overcome. Ultimately, this form of visualization via machine learning informs on the challenges faced with multiclass classification and adds insight into the decision-making process for a diagnosis and prognosis