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Register a new userDisentangling brain heterogeneity via semi-supervised deep-learning and MRI: dimensional representations of Alzheimers Disease
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Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a novel semi-supervised deep-clustering method, which dissects neuroanatomical heterogeneity, enabling identification of disease subtypes via their imaging signatures relative to controls. When applied to MRIs (2 studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified 4 neurodegenerative patterns/axes: P1, normal anatomy and highest cognitive performance; P2, mild/diffuse atrophy and more prominent executive dysfunction; P3, focal medial temporal atrophy and relatively greater memory impairment; P4, advanced neurodegeneration. Further application to longitudinal data revealed two distinct progression pathways: P1$rightarrow$P2$rightarrow$P4 and P1$rightarrow$P3$rightarrow$P4. Baseline expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered better yet complementary performance in predicting clinical progression, compared to amyloid/tau. These deep-learning derived biomarkers offer promise for precision diagnostics and targeted clinical trial recruitment.
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Neuroimaging biomarkers that distinguish between typical brain aging and Alzheimers disease (AD) are valuable for determining how much each contributes to cognitive decline. Machine learning models can derive multi-variate brain change patterns related to the two processes, including the SPARE-AD (Spatial Patterns of Atrophy for Recognition of Alzheimers Disease) and SPARE-BA (of Brain Aging) investigated herein. However, substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology toward disentangling the two. T1-weighted MRI images of 4,054 participants (48-95 years) with AD, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the iSTAGING (Imaging-based coordinate SysTem for AGIng and NeurodeGenerative diseases) consortium were analyzed. First, a subset of AD patients and CN adults were selected based purely on clinical diagnoses to train SPARE-BA1 (regression of age using CN individuals) and SPARE-AD1 (classification of CN versus AD). Second, analogous groups were selected based on clinical and molecular markers to train SPARE-BA2 and SPARE-AD2: amyloid-positive (A+) AD continuum group (consisting of A+AD, A+MCI, and A+ and tau-positive CN individuals) and amyloid-negative (A-) CN group. Finally, the combined group of the AD continuum and A-/CN individuals was used to train SPARE-BA3, with the intention to estimate brain age regardless of AD-related brain changes. Disentangled SPARE models derived brain patterns that were more specific to the two types of the brain changes. Correlation between the SPARE-BA and SPARE-AD was significantly reduced. Correlation of disentangled SPARE-AD was non-inferior to the molecular measurements and to the number of APOE4 alleles, but was less to AD-related psychometric test scores, suggesting contribution of advanced brain aging to these scores.
In recent years, many papers have reported state-of-the-art performance on Alzheimers Disease classification with MRI scans from the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset using convolutional neural networks. However, we discover that when we split that data into training and testing sets at the subject level, we are not able to obtain similar performance, bringing the validity of many of the previous studies into question. Furthermore, we point out that previous works use different subsets of the ADNI data, making comparison across similar works tricky. In this study, we present the results of three splitting methods, discuss the motivations behind their validity, and report our results using all of the available subjects.
The current state-of-the-art deep neural networks (DNNs) for Alzheimers 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 sparse categorical data, (ii) a Factorization Machine to efficiently learn pairwise interactions, and (iii) a DNN to implicitly model higher order interactions. In our experiments on data from the Alzheimers Disease Neuroimaging Initiative, we demonstrate that our proposed model classifies cognitive normal, mild cognitive impaired, and demented patients more accurately than competing models. In addition, we show that valuable knowledge about the interactions among biomarkers can be obtained.
Early and accurate diagnosis of Alzheimers disease (AD) and its prodromal period mild cognitive impairment (MCI) is essential for the delayed disease progression and the improved quality of patientslife. The emerging computer-aided diagnostic methods that combine deep learning with structural magnetic resonance imaging (sMRI) have achieved encouraging results, but some of them are limit of issues such as data leakage and unexplainable diagnosis. In this research, we propose a novel end-to-end deep learning approach for automated diagnosis of AD and localization of important brain regions related to the disease from sMRI data. This approach is based on a 2D single model strategy and has the following differences from the current approaches: 1) Convolutional Neural Network (CNN) models of different structures and capacities are evaluated systemically and the most suitable model is adopted for AD diagnosis; 2) a data augmentation strategy named Two-stage Random RandAugment (TRRA) is proposed to alleviate the overfitting issue caused by limited training data and to improve the classification performance in AD diagnosis; 3) an explainable method of Grad-CAM++ is introduced to generate the visually explainable heatmaps that localize and highlight the brain regions that our model focuses on and to make our model more transparent. Our approach has been evaluated on two publicly accessible datasets for two classification tasks of AD vs. cognitively normal (CN) and progressive MCI (pMCI) vs. stable MCI (sMCI). The experimental results indicate that our approach outperforms the state-of-the-art approaches, including those using multi-model and 3D CNN methods. The resultant localization heatmaps from our approach also highlight the lateral ventricle and some disease-relevant regions of cortex, coincident with the commonly affected regions during the development of AD.
Early detection is crucial to prevent the progression of Alzheimers disease (AD). Thus, specialists can begin preventive treatment as soon as possible. They demand fast and precise assessment in the diagnosis of AD in the earliest and hardest to detect stages. The main objective of this work is to develop a system that automatically detects the presence of the disease in sagittal magnetic resonance images (MRI), which are not generally used. Sagittal MRIs from ADNI and OASIS data sets were employed. Experiments were conducted using Transfer Learning (TL) techniques in order to achieve more accurate results. There are two main conclusions to be drawn from this work: first, the damages related to AD and its stages can be distinguished in sagittal MRI and, second, the results obtained using DL models with sagittal MRIs are similar to the state-of-the-art, which uses the horizontal-plane MRI. Although sagittal-plane MRIs are not commonly used, this work proved that they were, at least, as effective as MRI from other planes at identifying AD in early stages. This could pave the way for further research. Finally, one should bear in mind that in certain fields, obtaining the examples for a data set can be very expensive. This study proved that DL models could be built in these fields, whereas TL is an essential tool for completing the task with fewer examples.
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