Robust Modeling and Prediction of Disease Progression Using Machine Learning

This work studies modeling the progression of Alzheimer’s disease using a parametric method robust to outliers and missing data and a nonparametric method robust to missing values and training instabilities. The proposed parametric method linearly maps the individual’s age to a disease progression score (DPS) and jointly fits constrained generalized logistic functions to the longitudinal dynamics of biomarkers as functions of the DPS using M-estimation. The proposed nonparametric method applies a generalized training rule based on normalizing the input and loss to the number of available data points to the long short-term memory (LSTM) recurrent neural networks to handle missing input and target values. Moreover, a robust initialization method is developed to address the training instability in LSTM networks based on a scaled random initialization of the network weights, aiming at preserving the variance of the network input and output in the same range. Both proposed methods are evaluated on data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) for robust modeling of volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET) biomarkers, cerebrospinal fluid (CSF) measurements, as well as cognitive tests, and are compared to the state-of-the-art methods. The obtained results show that the proposed parametric model outperforms almost all state-of-the-art parametric methods in predicting biomarker values and classifying clinical status, and it generalizes well when applied to independent data from the National Alzheimer’s Coordinating Center (NACC). Additionally, the proposed generalized training rule for deep neural networks achieves superior results to standard LSTMs using data imputation before training, especially when applied to data with lower rates of missing values. A comprehensive analysis of the proposed methods in neurodegenerative disease progression modeling reveals that the proposed nonparametric method performs better than the proposed parametric method in predicting biomarker values, while the parametric method works significantly better in clinical status classification

Plant identification using deep convolutional networks based on principal component analysis

Plants have substantial effects in human vitality through their different uses in agriculture, food industry, pharmacology, and climate control. The large number of herbs and plant species and shortage of skilled botanists have increased the need for automated plant identification systems in recent years. As one of the challenging problems in object recognition, automatic plant identification aims to assign the plant in an image to a known taxon or species using machine learning and computer vision algorithms. However, this problem is challenging due to the inter-class similarities within a plant family and large intra-class variations in background, occlusion, pose, color, and illumination. In this thesis, we propose an automatic plant identification system based on deep convolutional networks. This system uses a simple baseline and applies principal component analysis (PCA) to patches of images to learn the network weights in an unsupervised learning approach. After multi-stage PCA filter banks are learned, a simple binary hashing is applied to output maps and the obtained maps are subsampled through max-pooling. Finally, the spatial pyramid pooling is applied to the downsampled data to extract features from block histograms. A multi-class linear support vector machine is then trained to classify the different species. The system performance is evaluated on the plant identification datasets of LifeCLEF 2014 in terms of classification accuracy, inverse rank score, and robustness against pose (translation, scaling, and rotation) and illumination variations. A comparison of our results with those of the top systems submitted to LifeCLEF 2014 campaign reveals that our proposed system would have achieved the second place in the categories of Entire, Branch, Fruit, Leaf, Scanned Leaf, and Stem, and the third place in the Flower category while having a simpler architecture and lower computational complexity than the winner system(s). We achieved the best accuracy in scanned leaves where we obtained an inverse rank score of 0.6157 and a classification accuracy of 68.25%

Combining Multiple Views for Visual Speech Recognition

Visual speech recognition is a challenging research problem with a particular practical application of aiding audio speech recognition in noisy scenarios. Multiple camera setups can be beneficial for the visual speech recognition systems in terms of improved performance and robustness. In this paper, we explore this aspect and provide a comprehensive study on combining multiple views for visual speech recognition. The thorough analysis covers fusion of all possible view angle combinations both at feature level and decision level. The employed visual speech recognition system in this study extracts features through a PCA-based convolutional neural network, followed by an LSTM network. Finally, these features are processed in a tandem system, being fed into a GMM-HMM scheme. The decision fusion acts after this point by combining the Viterbi path log-likelihoods. The results show that the complementary information contained in recordings from different view angles improves the results significantly. For example, the sentence correctness on the test set is increased from 76% for the highest performing single view ($30^\circ$) to up to 83% when combining this view with the frontal and $60^\circ$ view angles

Open-set plant identification using an ensemble of deep convolutional neural networks

Open-set recognition, a challenging problem in computer vision, is concerned with identification or verification tasks where queries may belong to unknown classes. This work describes a fine-grained plant identification system consisting of an ensemble of deep convolutional neural networks within an open-set identification framework. Two wellknown deep learning architectures of VGGNet and GoogLeNet, pretrained on the object recognition dataset of ILSVRC 2012, are finetuned using the plant dataset of LifeCLEF 2015. Moreover, GoogLeNet is fine-tuned using plant and non-plant images for rejecting samples from non-plant classes. Our systems have been evaluated on the test dataset of PlantCLEF 2016 by the campaign organizers and our best proposed model has achieved an official score of 0.738 in terms of the mean average precision, while the best official score is 0.742

Robust training of recurrent neural networks to handle missing data for disease progression modeling

Disease progression modeling (DPM) using longitudinal data is a challenging task in machine learning for healthcare that can provide clinicians with better tools for diagnosis and monitoring of disease. Existing DPM algorithms neglect temporal dependencies among measurements and make parametric assumptions about biomarker trajectories. In addition, they do not model multiple biomarkers jointly and need to align 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. We, therefore, propose a generalized training rule for the most widely used RNN architecture, long short-term memory (LSTM) networks, that can handle missing values in both target and predictor variables. This algorithm is applied for modeling the progression of Alzheimer's disease (AD) using magnetic resonance imaging (MRI) biomarkers. The results show that the proposed LSTM algorithm achieves a lower mean absolute error for prediction of measurements across all considered MRI biomarkers compared to using standard LSTM networks with data imputation or using a regression-based DPM method. Moreover, applying linear discriminant analysis to the biomarkers' values predicted by the proposed algorithm results in a larger area under the receiver operating characteristic curve (AUC) for clinical diagnosis of AD compared to the same alternatives, and the AUC is comparable to state-of-the-art AUCs from a recent cross-sectional medical image classification challenge. This paper shows that built-in handling of missing values in LSTM network training paves the way for application of RNNs in disease progression modeling.Comment: 9 pages, 1 figure, MIDL conferenc

Training recurrent neural networks robust to incomplete data: application to Alzheimer's disease progression modeling

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. Instead, we propose a generalized training rule for the most widely used RNN architecture, long short-term memory (LSTM) networks, that can handle both missing predictor and target values. The proposed LSTM algorithm is applied to model the progression of Alzheimer's disease (AD) using six volumetric magnetic resonance imaging (MRI) biomarkers, i.e., volumes of ventricles, hippocampus, whole brain, fusiform, middle temporal gyrus, and entorhinal cortex, and it is compared to standard LSTM networks with data imputation and a parametric, regression-based DPM method. The results show that the proposed algorithm achieves a significantly lower mean absolute error (MAE) than the alternatives with p < 0.05 using Wilcoxon signed rank test in predicting values of almost all of the MRI biomarkers. Moreover, a linear discriminant analysis (LDA) classifier applied to the predicted biomarker values produces a significantly larger AUC of 0.90 vs. at most 0.84 with p < 0.001 using McNemar's test for clinical diagnosis of AD. Inspection of MAE curves as a function of the amount of missing data reveals that the proposed LSTM algorithm achieves the best performance up until more than 74% missing values. Finally, it is illustrated how the method can successfully be applied to data with varying time intervals.Comment: arXiv admin note: substantial text overlap with arXiv:1808.0550

Robust parametric modeling of Alzheimer's disease progression

Quantitative characterization of disease progression using longitudinal data can provide long-term predictions for the pathological stages of individuals. This work studies the robust modeling of Alzheimer's disease progression using parametric methods. The proposed method linearly maps the individual's age to a disease progression score (DPS) and jointly fits constrained generalized logistic functions to the longitudinal dynamics of biomarkers as functions of the DPS using M-estimation. Robustness of the estimates is quantified using bootstrapping via Monte Carlo resampling, and the estimated inflection points of the fitted functions are used to temporally order the modeled biomarkers in the disease course. Kernel density estimation is applied to the obtained DPSs for clinical status classification using a Bayesian classifier. Different M-estimators and logistic functions, including a novel type proposed in this study, called modified Stannard, are evaluated on the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for robust modeling of volumetric MRI and PET biomarkers, CSF measurements, as well as cognitive tests. The results show that the modified Stannard function fitted using the logistic loss achieves the best modeling performance with an average normalized MAE of 0.991 across all biomarkers and bootstraps. Applied to the ADNI test set, this model achieves a multiclass AUC of 0.934 in clinical status classification. The obtained results for the proposed model outperform almost all state-of-the-art results in predicting biomarker values and classifying clinical status. Finally, the experiments show that the proposed model, trained using abundant ADNI data, generalizes well to data from the National Alzheimer's Coordinating Center (NACC) with an average normalized MAE of 1.182 and a multiclass AUC of 0.929