Normative modelling is an emerging method for understanding the underlying heterogeneity within brain disorders like Alzheimer Disease (AD) by quantifying how each patient deviates from the expected normative pattern that has been learned from a healthy control distribution. Since AD is a multifactorial disease with more than one biological pathways, multimodal magnetic resonance imaging (MRI) neuroimaging data can provide complementary information about the disease heterogeneity. However, existing deep learning based normative models on multimodal MRI data use unimodal autoencoders with a single encoder and decoder that may fail to capture the relationship between brain measurements extracted from different MRI modalities. In this work, we propose multi-modal variational autoencoder (mmVAE) based normative modelling framework that can capture the joint distribution between different modalities to identify abnormal brain structural patterns in AD. Our multi-modal framework takes as input Freesurfer processed brain region volumes from T1-weighted (cortical and subcortical) and T2-weighed (hippocampal) scans of cognitively normal participants to learn the morphological characteristics of the healthy brain. The estimated normative model is then applied on Alzheimer Disease (AD) patients to quantify the deviation in brain volumes and identify the abnormal brain structural patterns due to the effect of the different AD stages. Our experimental results show that modeling joint distribution between the multiple MRI modalities generates deviation maps that are more sensitive to disease staging within AD, have a better correlation with patient cognition and result in higher number of brain regions with statistically significant deviations compared to a unimodal baseline model with all modalities concatenated as a single input.
Lehigh University（利哈伊大学）；University of Illinois at Chicago（伊利诺伊大学芝加哥分校）；NYU Grossman School of Medicine（纽约大学格罗斯曼医学院）
Normative modeling is an emerging and promising approach to effectively study disorder heterogeneity in individual participants. In this study, we propose a novel normative modeling method by combining conditional variational autoencoder with adversarial learning (ACVAE) to identify brain dysfunction in Alzheimer's Disease (AD). Specifically, we first train a conditional VAE on the healthy control (HC) group to create a normative model conditioned on covariates like age, gender and intracranial volume. Then we incorporate an adversarial training process to construct a discriminative feature sp…
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）；School of Biomedical Engineering, Shenzhen University（深圳大学生物医学工程学院）；Gaoling School of Artificial Intelligence, Renmin University of China（中国人民大学高瓴人工智能学院）
One of the main reasons for Alzheimer's disease (AD) is the disorder of some neural circuits. Existing methods for AD prediction have achieved great success, however, detecting abnormal neural circuits from the perspective of brain networks is still a big challenge. In this work, a novel decoupling generative adversarial network (DecGAN) is proposed to detect abnormal neural circuits for AD. Concretely, a decoupling module is designed to decompose a brain network into two parts: one part is composed of a few sparse graphs which represent the neural circuits largely determining the development …
Improving Normative Modeling for Multi-modal Neuroimaging Data using mixture-of-product-of-experts variational autoencoders
Department of Computer Science and Engineering, Washington University in St. Louis, USA（计算机科学与工程系，华盛顿大学圣路易斯分校）；Institute for Informatics, Data Science and Biostatistics, Washington University in St.Louis, USA（信息学、数据科学与生物统计研究所，华盛顿大学圣路易斯分校）；Department of Radiology, Washington University in St.Louis, USA（放射学系，华盛顿大学圣路易斯分校）
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）；Shenzhen University（深圳大学）；Renmin University of China（中国人民大学）；Central South University（中南大学）
Alzheimer's disease is characterized by alterations of the brain's structural and functional connectivity during its progressive degenerative processes. Existing auxiliary diagnostic methods have accomplished the classification task, but few of them can accurately evaluate the changing characteristics of brain connectivity. In this work, a prior guided adversarial representation learning and hypergraph perceptual network (PGARL-HPN) is proposed to predict abnormal brain connections using triple-modality medical images. Concretely, a prior distribution from the anatomical knowledge is estimated…
CADD: Context aware disease deviations via restoration of brain images using normative conditional diffusion models
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School（阿提诺拉A.马丁纳生物医学成像中心，麻省总医院和哈佛医学院）；Hawkes Institute, University College London（霍克斯研究所，伦敦大学学院）；Mecha Health（Mecha健康）；Computer Science & Artificial Intelligence Lab, Massachusetts Institute of Technology（计算机科学与人工智能实验室，麻省理工学院）；Department of Radiology, the University of Tokyo（东京大学放射科）；Medical Engineering, Chiba University（千叶大学医学工程）；Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital（东京大学医院计算诊断放射学与预防医学科）
Erasmus MC（伊拉斯姆斯医学中心）；Delft University of Technology（代尔夫特理工大学）；University of Copenhagen（哥本哈根大学）
Event-based models (EBM) are a class of disease progression models that can be used to estimate temporal ordering of neuropathological changes from cross-sectional data. Current EBMs only handle scalar biomarkers, such as regional volumes, as inputs. However, regional aggregates are a crude summary of the underlying high-resolution images, potentially limiting the accuracy of EBM. Therefore, we propose a novel method that exploits high-dimensional voxel-wise imaging biomarkers: n-dimensional discriminative EBM (nDEBM). nDEBM is based on an insight that mixture modeling, which is a key element …
Alzheimer's disease and Frontotemporal dementia are two major types of dementia. Their accurate diagnosis and differentiation is crucial for determining specific intervention and treatment. However, differential diagnosis of these two types of dementia remains difficult at the early stage of disease due to similar patterns of clinical symptoms. Therefore, the automatic classification of multiple types of dementia has an important clinical value. So far, this challenge has not been actively explored. Recent development of deep learning in the field of medical image has demonstrated high perform…
Tianjin University（天津大学）；Kunming University of Science and Technology（昆明理工大学）；Tianjin Dementia Institute（天津痴呆研究所）；Tianjin Huanhu Hospital（天津环湖医院）
Alzheimer's Disease (AD) causes a continuous decline in memory, thinking, and judgment. Traditional diagnoses are usually based on clinical experience, which is limited by some realistic factors. In this paper, we focus on exploiting deep learning techniques to diagnose AD based on eye-tracking behaviors. Visual attention, as typical eye-tracking behavior, is of great clinical value to detect cognitive abnormalities in AD patients. To better analyze the differences in visual attention between AD patients and normals, we first conduct a 3D comprehensive visual task on a non-invasive eye-trackin…
Alzheimer's disease (AD) is the most common age-related dementia. Mild cognitive impairment (MCI) is the early stage of cognitive decline before AD. It is crucial to predict the MCI-to-AD conversion for precise management, which remains challenging due to the diversity of patients. Previous evidence shows that the brain network generated from diffusion MRI promises to classify dementia using deep learning. However, the limited availability of diffusion MRI challenges the model training. In this study, we develop a self-supervised contrastive learning approach to generate structural brain netwo…
Alzheimer's Disease is the most common cause of dementia. Accurate diagnosis and prognosis of this disease are essential to design an appropriate treatment plan, increasing the life expectancy of the patient. Intense research has been conducted on the use of machine learning to identify Alzheimer's Disease from neuroimaging data, such as structural magnetic resonance imaging. In recent years, advances of deep learning in computer vision suggest a new research direction for this problem. Current deep learning-based approaches in this field, however, have a number of drawbacks, including the int…
LPIXEL Inc.（LPIXEL公司）；University of Cambridge（剑桥大学）；National Institute of Informatics（国立信息学研究所）；National Center for Global Health and Medicine（国立国际医疗研究中心）；Juntendo University（顺天堂大学）；ELTE Eötvös Loránd University（厄特沃什·罗兰大学）；The University of Tokyo（东京大学）
Unsupervised learning can discover various unseen abnormalities, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a 2D/3D single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer's Disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with eith…
Bias in Unsupervised Anomaly Detection in Brain MRI
Technical University of Munich（慕尼黑工业大学）；Helmholtz AI（亥姆霍兹人工智能研究所）；Helmholtz Center Munich（亥姆霍兹慕尼黑中心）；King’s College London（伦敦国王学院）；Klinikum Rechts der Isar（伊萨尔河畔临床教学中心）；Imperial College London（帝国理工学院）
