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

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

Alzheimer Disease Detection Techniques and Methods: A Review

Brain pathological changes linked with Alzheimer's disease (AD) can be measured with Neuroimaging. In the past few years, these measures are rapidly integrated into the signatures of Alzheimer disease (AD) with the help of classification frameworks which are offering tools for diagnosis and prognosis. Here is the review study of Alzheimer's disease based on Neuroimaging and cognitive impairment classification. This work is a systematic review for the published work in the field of AD especially the computer-aided diagnosis. The imaging modalities include 1) Magnetic resonance imaging (MRI) 2) Functional MRI (fMRI) 3) Diffusion tensor imaging 4) Positron emission tomography (PET) and 5) amyloid-PET. The study revealed that the classification criterion based on the features shows promising results to diagnose the disease and helps in clinical progression. The most widely used machine learning classifiers for AD diagnosis include Support Vector Machine, Bayesian Classifiers, Linear Discriminant Analysis, and K-Nearest Neighbor along with Deep learning. The study revealed that the deep learning techniques and support vector machine give higher accuracies in the identification of Alzheimer’s disease. The possible challenges along with future directions are also discussed in the paper

An effective feature selection using improved marine predators algorithm for Alzheimer’s disease classification

Alzheimer’s disease (AD) is an irremediable neurodegenerative illness developed by the fast deterioration of brain cells. AD is mostly common in elder people and it extremely disturbs the physical and mental health of patients, therefore early detection is essential to prevent AD development. However, the precise detection of AD and mild cognitive impairment (MCI) is difficult during classification. In this paper, the Residual network i.e., ResNet-18 is used for extracting the features, and the proposed improved marine predators algorithm (IMPA) is developed for choosing the optimum features to perform an effective classification of AD. The multi-verse optimizer (MVO) used in the IMPA helps to balance exploration and exploitation, which leads to the selection of optimal relevant features. Further, the classification of AD is accomplished using the multiclass support vector machine (MSVM). Open access series of imaging studies-1 (OASIS-1) and Alzheimer disease neuroimaging initiative (ADNI) datasets are used to evaluate the IMPA-MSVM method. The performance of the IMPA-MSVM method is analyzed using accuracy, sensitivity, specificity, positive predictive value (PPV) and matthews correlation coefficient (MCC). The existing methods such as the deep learning-based segmenting method using SegNet (DLSS), mish activation function (MAF) with spatial transformer network (STN) and BrainNet2D are used to evaluate the IMPA-MSVM method. The accuracy of IMPA-MSVM for the ADNI dataset is 98.43% which is more when compared to the DLSS and MAF-STN

Deep Interpretability Methods for Neuroimaging

Brain dynamics are highly complex and yet hold the key to understanding brain function and dysfunction. The dynamics captured by resting-state functional magnetic resonance imaging data are noisy, high-dimensional, and not readily interpretable. The typical approach of reducing this data to low-dimensional features and focusing on the most predictive features comes with strong assumptions and can miss essential aspects of the underlying dynamics. In contrast, introspection of discriminatively trained deep learning models may uncover disorder-relevant elements of the signal at the level of individual time points and spatial locations. Nevertheless, the difficulty of reliable training on high-dimensional but small-sample datasets and the unclear relevance of the resulting predictive markers prevent the widespread use of deep learning in functional neuroimaging. In this dissertation, we address these challenges by proposing a deep learning framework to learn from high-dimensional dynamical data while maintaining stable, ecologically valid interpretations. The developed model is pre-trainable and alleviates the need to collect an enormous amount of neuroimaging samples to achieve optimal training. We also provide a quantitative validation module, Retain and Retrain (RAR), that can objectively verify the higher predictability of the dynamics learned by the model. Results successfully demonstrate that the proposed framework enables learning the fMRI dynamics directly from small data and capturing compact, stable interpretations of features predictive of function and dysfunction. We also comprehensively reviewed deep interpretability literature in the neuroimaging domain. Our analysis reveals the ongoing trend of interpretability practices in neuroimaging studies and identifies the gaps that should be addressed for effective human-machine collaboration in this domain. This dissertation also proposed a post hoc interpretability method, Geometrically Guided Integrated Gradients (GGIG), that leverages geometric properties of the functional space as learned by a deep learning model. With extensive experiments and quantitative validation on MNIST and ImageNet datasets, we demonstrate that GGIG outperforms integrated gradients (IG), which is considered to be a popular interpretability method in the literature. As GGIG is able to identify the contours of the discriminative regions in the input space, GGIG may be useful in various medical imaging tasks where fine-grained localization as an explanation is beneficial

Investigation of Multi-dimensional Tensor Multi-task Learning for Modeling Alzheimer's Disease Progression

Machine learning (ML) techniques for predicting Alzheimer's disease (AD) progression can significantly assist clinicians and researchers in constructing effective AD prevention and treatment strategies. The main constraints on the performance of current ML approaches are prediction accuracy and stability problems in medical small dataset scenarios, monotonic data formats (loss of multi-dimensional knowledge of the data and loss of correlation knowledge between biomarkers) and biomarker interpretability limitations. This thesis investigates how multi-dimensional information and knowledge from biomarker data integrated with multi-task learning approaches to predict AD progression. Firstly, a novel similarity-based quantification approach is proposed with two components: multi-dimensional knowledge vector construction and amalgamated magnitude-direction quantification of brain structural variation, which considers both the magnitude and directional correlations of structural variation between brain biomarkers and encodes the quantified data as a third-order tensor to address the problem of monotonic data form. Secondly, multi-task learning regression algorithms with the ability to integrate multi-dimensional tensor data and mine MRI data for spatio-temporal structural variation information and knowledge were designed and constructed to improve the accuracy, stability and interpretability of AD progression prediction in medical small dataset scenarios. The algorithm consists of three components: supervised symmetric tensor decomposition for extracting biomarker latent factors, tensor multi-task learning regression and algorithmic regularisation terms. The proposed algorithm aims to extract a set of first-order latent factors from the raw data, each represented by its first biomarker, second biomarker and patient sample dimensions, to elucidate potential factors affecting the variability of the data in an interpretable manner and can be utilised as predictor variables for training the prediction model that regards the prediction of each patient as a task, with each task sharing a set of biomarker latent factors obtained from tensor decomposition. Knowledge sharing between tasks improves the generalisation ability of the model and addresses the problem of sparse medical data. The experimental results demonstrate that the proposed approach achieves superior accuracy and stability in predicting various cognitive scores of AD progression compared to single-task learning, benchmarks and state-of-the-art multi-task regression methods. The proposed approach identifies brain structural variations in patients and the important brain biomarker correlations revealed by the experiments can be utilised as potential indicators for AD early identification

Quantifying cognitive and mortality outcomes in older patients following acute illness using epidemiological and machine learning approaches

Introduction: Cognitive and functional decompensation during acute illness in older people are poorly understood. It remains unclear how delirium, an acute confusional state reflective of cognitive decompensation, is contextualised by baseline premorbid cognition and relates to long-term adverse outcomes. High-dimensional machine learning offers a novel, feasible and enticing approach for stratifying acute illness in older people, improving treatment consistency while optimising future research design. Methods: Longitudinal associations were analysed from the Delirium and Population Health Informatics Cohort (DELPHIC) study, a prospective cohort ≥70 years resident in Camden, with cognitive and functional ascertainment at baseline and 2-year follow-up, and daily assessments during incident hospitalisation. Second, using routine clinical data from UCLH, I constructed an extreme gradient-boosted trees predicting 600-day mortality for unselected acute admissions of oldest-old patients with mechanistic inferences. Third, hierarchical agglomerative clustering was performed to demonstrate structure within DELPHIC participants, with predictive implications for survival and length of stay. Results: i. Delirium is associated with increased rates of cognitive decline and mortality risk, in a dose-dependent manner, with an interaction between baseline cognition and delirium exposure. Those with highest delirium exposure but also best premorbid cognition have the “most to lose”. ii. High-dimensional multimodal machine learning models can predict mortality in oldest-old populations with 0.874 accuracy. The anterior cingulate and angular gyri, and extracranial soft tissue, are the highest contributory intracranial and extracranial features respectively. iii. Clinically useful acute illness subtypes in older people can be described using longitudinal clinical, functional, and biochemical features. Conclusions: Interactions between baseline cognition and delirium exposure during acute illness in older patients result in divergent long-term adverse outcomes. Supervised machine learning can robustly predict mortality in in oldest-old patients, producing a valuable prognostication tool using routinely collected data, ready for clinical deployment. Preliminary findings suggest possible discernible subtypes within acute illness in older people

Multi-Modal Magnetic Resonance Imaging Predicts Regional Amyloid Burden in the Brain

Alzheimer’s disease (AD) is the most common cause of dementia and identifying early markers of this disease is important for prevention and treatment strategies. Amyloid- β (Aβ) protein deposition is one of the earliest detectable pathological changes in AD. But in-vivo detection of Aβ using positron emission tomography (PET) is hampered by high cost and limited geographical accessibility. These factors can become limiting when PET is used to screen large numbers of subjects into prevention trials when only a minority are expected to be amyloid-positive. Structural MRI is advantageous; as it is non-invasive, relatively inexpensive and more accessible. Thus it could be widely used in large studies, even when frequent or repetitive imaging is necessary. We used a machine learning, pattern recognition, approach using intensity-based features from individual and combination of MR modalities (T1 weighted, T2 weighted, T2 fluid attenuated inversion recovery [FLAIR], susceptibility weighted imaging) to predict voxel-level amyloid in the brain. The MR- Aβ relation was learned within each subject and generalized across subjects using subject–specific features (demographic, clinical, and summary MR features). When compared to other modalities, combination of T1-weighted, T2-weighted FLAIR, and SWI performed best in predicting the amyloid status as positive or negative. A combination of T2-weighted and SWI imaging performed the best in predicting change in amyloid over two timepoints. Overall, our results show feasibility of amyloid prediction by MRI and its potential use as an amyloid-screening tool

Integrated Structural And Functional Biomarkers For Neurodegeneration

Alzheimer\u27s Disease consists of a complex cascade of pathological processes, leading to the death of cortical neurons and development of dementia. Because it is impossible to regenerate neurons that have already died, a thorough understanding of the earlier stages of the disease, before significant neuronal death has occurred, is critical for developing disease-modifying therapies. The various components of Alzheimer\u27s Disease pathophysiology necessitate a variety of measurement techniques. Image-based measurements known as biomarkers can be used to assess cortical thinning and cerebral blood flow, but non-imaging characteristics such as performance on cognitive tests and age are also important determinants of risk of Alzheimer\u27s Disease. Incorporating the various imaging and non-imaging sources of information into a scientifically interpretable and statistically sound model is challenging. In this thesis, I present a method to include imaging data in standard regression analyses in a data-driven and anatomically interpretable manner. I also introduce a technique for disentangling the effect of cortical structure from blood flow, enabling a clearer picture of the signal carried by cerebral blood flow beyond the confounding effects of anatomical structure. In addition to these technical developments in multi-modal image analysis, I show the results of two clinically-oriented studies focusing on the relative importance of various biomarkers for predicting presence of Alzheimer\u27s Disease pathology in the earliest stages of disease. In the first, I present evidence that white matter hyperintensities, a marker of small vessel disease, are more highly associated with Alzheimer\u27s Disease pathology than current mainstream imaging biomarkers in elderly control patients. In the second, I show that once Alzheimer\u27s Disease has progressed to the point of noticeable cognitive decline, cognitive tests are as predictive of presence of Alzheimer\u27s pathology as standard imaging biomarkers. Taken together, these studies demonstrate that the relative importance of biomarkers and imaging modalities changes over the course of disease progression, and sophisticated data-driven methods for combining a variety of modalities is likely to lead to greater biological insight into the disease process than a single modality