Self-Supervised Multimodal Domino: in Search of Biomarkers for Alzheimer's Disease
Georgia Institute of Technology（佐治亚理工学院）；Georgia State University（佐治亚州立大学）；Emory University（埃默里大学）；Center for Translational Research in Neuroimaging and Data Science（神经影像学与数据科学转化研究中心）；Mila - Quebec AI Institute（米拉-魁北克人工智能研究所）；Université de Montréal（蒙特利尔大学）；Delft University of Technology（代尔夫特理工大学）
Alex Fedorov, Tristan Sylvain, Eloy Geenjaar, Margaux Luck, Lei Wu, Thomas P. DeRamus, Alex Kirilin, Dmitry Bleklov, Vince D. Calhoun, Sergey M. Plis
Sensory input from multiple sources is crucial for robust and coherent human perception. Different sources contribute complementary explanatory factors. Similarly, research studies often collect multimodal imaging data, each of which can provide shared and unique information. This observation motivated the design of powerful multimodal self-supervised representation-learning algorithms. In this paper, we unify recent work on multimodal self-supervised learning under a single framework. Observing that most self-supervised methods optimize similarity metrics between a set of model components, we propose a taxonomy of all reasonable ways to organize this process. We first evaluate models on toy multimodal MNIST datasets and then apply them to a multimodal neuroimaging dataset with Alzheimer's disease patients. We find that (1) multimodal contrastive learning has significant benefits over its unimodal counterpart, (2) the specific composition of multiple contrastive objectives is critical to performance on a downstream task, (3) maximization of the similarity between representations has a regularizing effect on a neural network, which can sometimes lead to reduced downstream performance but still reveal multimodal relations. Results show that the proposed approach outperforms previous self-supervised encoder-decoder methods based on canonical correlation analysis (CCA) or the mixture-of-experts multimodal variational autoEncoder (MMVAE) on various datasets with a linear evaluation protocol. Importantly, we find a promising solution to uncover connections between modalities through a jointly shared subspace that can help advance work in our search for neuroimaging biomarkers.
Ludwig-Maximilians-Universität（路德维希-马克西米利安大学）；Indiana University School of Medicine（印第安纳大学医学院）
The current state-of-the-art deep neural networks (DNNs) for Alzheimer's Disease diagnosis use different biomarker combinations to classify patients, but do not allow extracting knowledge about the interactions of biomarkers. However, to improve our understanding of the disease, it is paramount to extract such knowledge from the learned model. In this paper, we propose a Deep Factorization Machine model that combines the ability of DNNs to learn complex relationships and the ease of interpretability of a linear model. The proposed model has three parts: (i) an embedding layer to deal with spar…
Due to the rapid innovation of technology and the desire to find and employ biomarkers for neurodegenerative disease, high-dimensional data classification problems are routinely encountered in neuroimaging studies. To avoid over-fitting and to explore relationships between disease and potential biomarkers, feature learning and selection plays an important role in classifier construction and is an important area in machine learning. In this article, we review several important feature learning and selection techniques including lasso-based methods, PCA, the two-sample t-test, and stacked auto-e…
Towards early diagnosis of Alzheimer's disease: Advances in immune-related blood biomarkers and computational modeling approaches
Fraunhofer Institute for Algorithms and Scientific Computing (SCAI)（弗劳恩霍夫算法与科学计算研究所（SCAI））；University of Bonn（波恩大学）；Tel Aviv University（特拉维夫大学）；Hospital Clínic de Barcelona（巴塞罗那临床医院）；University of Barcelona（巴塞罗那大学）；ImmunoBrain Checkpoint Ltd.（ImmunoBrain Checkpoint有限公司）；Sagol School of Neuroscience（萨戈尔神经科学学院）
Healthcare datasets present many challenges to both machine learning and statistics as their data are typically heterogeneous, censored, high-dimensional and have missing information. Feature selection is often used to identify the important features but can produce unstable results when applied to high-dimensional data, selecting a different set of features on each iteration. The stability of feature selection can be improved with the use of feature selection ensembles, which aggregate the results of multiple base feature selectors. A threshold must be applied to the final aggregated feature …
Healthcare datasets often contain groups of highly correlated features, such as features from the same biological system. When feature selection is applied to these datasets to identify the most important features, the biases inherent in some multivariate feature selectors due to correlated features make it difficult for these methods to distinguish between the important and irrelevant features and the results of the feature selection process can be unstable. Feature selection ensembles, which aggregate the results of multiple individual base feature selectors, have been investigated as a mean…
Enabling Few-Shot Alzheimer's Disease Diagnosis on Biomarker Data with Tabular LLMs
University of Pennsylvania（宾夕法尼亚大学）；United States Naval Academy（美国海军学院）；University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）；Cedars Sinai Medical Center（西好莱坞 Cedars Sinai 医院）
Predicting Early Stages Of Alzheimer's Disease And Identifying Key Biomarkers Using Deep Artificial Neural Network And Ensemble Of Machine Learning Methodologies
The Ohio State University（俄亥俄州立大学）；University of Pennsylvania（宾夕法尼亚大学）；Indiana University（印第安纳大学）
Background:Cognitive assessments represent the most common clinical routine for the diagnosis of Alzheimer's 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 lear…
Unravelling Causal Genetic Biomarkers of Alzheimer's Disease via Neuron to Gene-token Backtracking in Neural Architecture: A Groundbreaking Reverse-Gene-Finder Approach
Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers
Washington University in St Louis（圣路易斯华盛顿大学）；Washington University School of Medicine in St Louis（圣路易斯华盛顿大学医学院）；Mallinckrodt Institute of Radiology（马林克罗特放射学研究所）
Biomediq A/S（Biomediq公司）；Cerebriu A/S（Cerebriu公司）；University of Copenhagen（哥本哈根大学）；University College London（伦敦大学学院）；King’s College London（伦敦国王学院）
Disease progression modeling (DPM) using longitudinal data is a challenging machine learning task. Existing DPM algorithms neglect temporal dependencies among measurements, make parametric assumptions about biomarker trajectories, do not model multiple biomarkers jointly, and need an alignment of subjects' trajectories. In this paper, recurrent neural networks (RNNs) are utilized to address these issues. However, in many cases, longitudinal cohorts contain incomplete data, which hinders the application of standard RNNs and requires a pre-processing step such as imputation of the missing values…
Forecasting Medium-Horizon Alzheimer's Disease Progression: Residual Gap-Aware Transformers for 24-Month CDR-SB Change from ADNI Clinical and Biomarker Histories
Department of Mathematical Sciences, University of Texas at Dallas（德克萨斯大学达拉斯分校数学科学系）；Department of Plant Science and Landscape Architecture, University of Connecticut（康奈尔大学植物科学与景观建筑系）；Naveen Jindal School of Management, University of Texas at Dallas（德克萨斯大学达拉斯分校纳文·金达管理学院）；Zhejiang Provincial People’s Hospital（浙江省人民医院）
Lehigh University（里海大学）；University of Pennsylvania（宾夕法尼亚大学）
Identification of brain regions related to the specific neurological disorders are of great importance for biomarker and diagnostic studies. In this paper, we propose an interpretable Graph Convolutional Network (GCN) framework for the identification and classification of Alzheimer's disease (AD) using multi-modality brain imaging data. Specifically, we extended the Gradient Class Activation Mapping (Grad-CAM) technique to quantify the most discriminative features identified by GCN from brain connectivity patterns. We then utilized them to find signature regions of interest (ROIs) by detecting…
Early Detection of Alzheimer's Disease Using Explainable Machine Learning on Clinical Biomarkers: A Multi-Class Classification Study Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) Dataset
Towards improving Alzheimer's intervention: a machine learning approach for biomarker detection through combining MEG and MRI pipelines
Universiti Teknologi PETRONAS（马来西亚国油大学）；Hospital Universiti Sains Malaysia（马来西亚理科大学医院）；Universiti Sains Malaysia（马来西亚理科大学）；Ulster University（阿尔斯特大学）；University of Calgary（卡尔加里大学）；University of Bath（巴斯大学）
本文基于 324 名 BioFIND 参与者的 MEG 与 MRI 数据，通过交叉验证机器学习分类识别 MCI，发现融合未校正 MEG 与 z-score 校正 MRI 特征效果最佳。
We introduce a wide and deep neural network for prediction of progression from patients with mild cognitive impairment to Alzheimer's disease. Information from anatomical shape and tabular clinical data (demographics, biomarkers) are fused in a single neural network. The network is invariant to shape transformations and avoids the need to identify point correspondences between shapes. To account for right censored time-to-event data, i.e., when it is only known that a patient did not develop Alzheimer's disease up to a particular time point, we employ a loss commonly used in survival analysis.…
Longitudinal Progression Prediction of Alzheimer's Disease with Tabular Foundation Model
Department of Computer Science Emory University Atlanta GA USA（埃默里大学计算机科学系）；Center for Data Science Nell Hodgson Woodruff School of Nursing Emory University Atlanta GA USA（埃默里大学数据科学中心）；Department of Computer Science Georgia State University Atlanta GA USA（佐治亚州立大学计算机科学系）；Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) Atlanta GA USA（神经影像与数据科学转化研究三机构中心（TReNDS））
Univ. Bordeaux（波尔多大学）；CNRS（法国国家科学研究中心）；Bordeaux INP（波尔多国立高等物理、数学与信息技术学院）；Universitat Politècnia de València（瓦伦西亚理工大学）
Alzheimer's disease is the most common dementia leading to an irreversible neurodegenerative process. To date, subject revealed advanced brain structural alterations when the diagnosis is established. Therefore, an earlier diagnosis of this dementia is crucial although it is a challenging task. Recently, many studies have proposed biomarkers to perform early detection of Alzheimer's disease. Some of them have proposed methods based on inter-subject similarity while other approaches have investigated framework using intra-subject variability. In this work, we propose a novel framework combining…
Cross-Modality Translation with Generative Adversarial Networks to Unveil Alzheimer's Disease Biomarkers
School of Electrical and Computer Engineering, Georgia Institute of Technology（佐治亚理工学院电气与计算机工程学院）；Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University（佐治亚州立大学神经影像学与数据科学转化研究三机构中心（TReNDS））；College of Pharmacy, University of Florida（佛罗里达大学药学院）
Technical University Munich（慕尼黑工业大学）；Ludwig Maximilians University（慕尼黑大学）
Alzheimer's disease (AD) has a complex and multifactorial etiology, which requires integrating information about neuroanatomy, genetics, and cerebrospinal fluid biomarkers for accurate diagnosis. Hence, recent deep learning approaches combined image and tabular information to improve diagnostic performance. However, the black-box nature of such neural networks is still a barrier for clinical applications, in which understanding the decision of a heterogeneous model is integral. We propose PANIC, a prototypical additive neural network for interpretable AD classification that integrates 3D image…
OPTIMUS: Predicting Multivariate Outcomes in Alzheimer's Disease Using Multi-modal Data amidst Missing Values
University Lausanne Hospital (CHUV)（洛桑大学医院）；University of Lausanne (UNIL)（洛桑大学）；Zhejiang University（浙江大学）；Zhejiang University School of Medicine（浙江大学医学院）
Lehigh University（理海大学）；University of Pittsburgh（匹兹堡大学）；The Perelman School of Medicine, University of Pennsylvania（宾夕法尼亚大学佩雷尔曼医学院）
The assessment of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) associated with brain changes remains a challenging task. Recent studies have demonstrated that combination of multi-modality imaging techniques can better reflect pathological characteristics and contribute to more accurate diagnosis of AD and MCI. In this paper, we propose a novel tensor-based multi-modality feature selection and regression method for diagnosis and biomarker identification of AD and MCI from normal controls. Specifically, we leverage the tensor structure to exploit high-level correlation informati…
Alzheimer's disease (AD) is known as one of the major causes of dementia and is characterized by slow progression over several years, with no treatments or available medicines. In this regard, there have been efforts to identify the risk of developing AD in its earliest time. While many of the previous works considered cross-sectional analysis, more recent studies have focused on the diagnosis and prognosis of AD with longitudinal or time series data in a way of disease progression modeling (DPM). Under the same problem settings, in this work, we propose a novel computational framework that ca…
Institute for Applied Computational Science, Harvard John A. Paulson School of Engineering and Applied Sciences（哈佛大学约翰·A·保尔森工程与应用科学学院应用计算科学研究所）
Alzheimer's Disease (AD) ravages the cognitive ability of more than 5 million Americans and creates an enormous strain on the health care system. This paper proposes a machine learning predictive model for AD development without medical imaging and with fewer clinical visits and tests, in hopes of earlier and cheaper diagnoses. That earlier diagnoses could be critical in the effectiveness of any drug or medical treatment to cure this disease. Our model is trained and validated using demographic, biomarker and cognitive test data from two prominent research studies: Alzheimer's Disease Neuroima…
Erasmus MC, University Medical Center Rotterdam（鹿特丹伊拉斯姆斯医学中心（鹿特丹大学医学中心））；Delft University of Technology（代尔夫特理工大学）
Alzheimer's Disease (AD) is characterized by a cascade of biomarkers becoming abnormal, the pathophysiology of which is very complex and largely unknown. Event-based modeling (EBM) is a data-driven technique to estimate the sequence in which biomarkers for a disease become abnormal based on cross-sectional data. It can help in understanding the dynamics of disease progression and facilitate early diagnosis and prognosis. In this work we propose a novel discriminative approach to EBM, which is shown to be more accurate than existing state-of-the-art EBM methods. The method first estimates for e…
Tabular LLMs for Interpretable Few-Shot Alzheimer's Disease Prediction with Multimodal Biomedical Data
University of Pennsylvania（宾夕法尼亚大学）；Stony Brook University（石溪大学）；University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）；Medical University of South Carolina（南卡罗来纳医科大学）；Cedars-Sinai Medical Center（西格拉姆山医疗中心）
Explainable Graph Neural Networks: Understanding Brain Connectivity and Biomarkers in Dementia
School of Computing Technologies RMIT University Melbourne VIC Australia；Department of Biological Sciences；Department of Computer Science \& Information Systems Birla Institute of Technology；Institute of Innovation, Science；Sustainability Federation University Australia Ballarat VIC Australia；RMIT University；Birla Institute of Technology；Federation University Australia
Universidad del País Vasco/Euskal Herriko Unibertsitatea（巴斯克大学）；Fundació Tecnocampus（Tecnocampus基金会）；University of Vic – Central University of Catalonia（维克大学-加泰罗尼亚中央大学）；Universidad de Las Palmas de Gran Canaria（拉斯帕尔马斯大加那利大学）；Brn GuABIAN, Association for Personal Autonomy（GuABIAN 个人自主协会）
Most of medical developments require the ability to identify samples that are anomalous with respect to a target group or control group, in the sense they could belong to a new, previously unseen class or are not class data. In this case when there are not enough data to train two-class One-class classification appear like an available solution. On the other hand non-linear approaches could give very useful information. The aim of our project is to contribute to earlier diagnosis of AD and better estimates of its severity by using automatic analysis performed through new biomarkers extracted f…
Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Early diagnosis is critical for patients to benefit from potential intervention and treatment. The retina has been hypothesized as a diagnostic site for AD detection owing to its anatomical connection with the brain. Developed AI models for this purpose have yet to provide a rational explanation about the decision and neither infer the stage of disease's progression. Along this direction, we propose a novel model-agnostic explainable-AI framework, called Granular Neuron-level Explainer (LAVA)…
An Interpretable Ensemble Framework for Multi-Omics Dementia Biomarker Discovery Under HDLSS Conditions
Department of Mathematics and Physics, Mathematics Major, Gangneung-Wonju National University（数学与物理系，数学专业，江陵-Wonju国立大学）；Department of Data Science, Gangneung-Wonju National University（数据科学系，江陵-Wonju国立大学）
University of Louisville（路易斯维尔大学）；University of Auckland（奥克兰大学）
Early diagnosis, playing an important role in preventing progress and treating the Alzheimer's disease (AD), is based on classification of features extracted from brain images. The features have to accurately capture main AD-related variations of anatomical brain structures, such as, e.g., ventricles size, hippocampus shape, cortical thickness, and brain volume. This paper proposes to predict the AD with a deep 3D convolutional neural network (3D-CNN), which can learn generic features capturing AD biomarkers and adapt to different domain datasets. The 3D-CNN is built upon a 3D convolutional au…
Early diagnosis, playing an important role in preventing progress and treating the Alzheimer\{'}s disease (AD), is based on classification of features extracted from brain images. The features have to accurately capture main AD-related variations of anatomical brain structures, such as, e.g., ventricles size, hippocampus shape, cortical thickness, and brain volume. This paper proposed to predict the AD with a deep 3D convolutional neural network (3D-CNN), which can learn generic features capturing AD biomarkers and adapt to different domain datasets. The 3D-CNN is built upon a 3D convolutional…
Diagnosing Alzheimer's disease (AD) involves a deliberate diagnostic process owing to its innate traits of irreversibility with subtle and gradual progression. These characteristics make AD biomarker identification from structural brain imaging (e.g., structural MRI) scans quite challenging. Furthermore, there is a high possibility of getting entangled with normal aging. We propose a novel deep-learning approach through eXplainable AD Likelihood Map Estimation (XADLiME) for AD progression modeling over 3D sMRIs using clinically-guided prototype learning. Specifically, we establish a set of top…
The Charles Stark Draper Laboratory, Inc.（查尔斯·斯塔克·德雷珀实验室有限公司）
Accurate diagnosis of Alzheimer's Disease (AD) entails clinical evaluation of multiple cognition metrics and biomarkers. Metrics such as the Alzheimer's Disease Assessment Scale - Cognitive test (ADAS-cog) comprise multiple subscores that quantify different aspects of a patient's cognitive state such as learning, memory, and language production/comprehension. Although computer-aided diagnostic techniques for classification of a patient's current disease state exist, they provide little insight into the relationship between changes in brain structure and different aspects of a patient's cogniti…
Robust Multi-Omics Integration from Incomplete Modalities Significantly Improves Prediction of Alzheimer's Disease
LG AI Research, Seoul, Republic of Korea（LG AI研究院，韩国首尔）；Department of Chemistry, Seoul National University, Seoul, Republic of Korea（首尔国立大学化学系）；The Jackson Laboratory, Bar Harbor, Maine, USA（杰克逊实验室，缅因州巴尔 Harbor）
