Identification of progressive mild cognitive impairment patients using incomplete longitudinal MRI scans

Distinguishing progressive mild cognitive impairment (pMCI) from stable mild cognitive impairment (sMCI) is critical for identification of patients who are at-risk for Alzheimer’s disease (AD), so that early treatment can be administered. In this paper, we propose a pMCI/sMCI classification framework that harnesses information available in longitudinal magnetic resonance imaging (MRI) data, which could be incomplete, to improve diagnostic accuracy. Volumetric features were first extracted from the baseline MRI scan and subsequent scans acquired after 6, 12, and 18 months. Dynamic features were then obtained by using the 18th-month scan as the reference and computing the ratios of feature differences for the earlier scans. Features that are linearly or non-linearly correlated with diagnostic labels are then selected using two elastic net sparse learning algorithms. Missing feature values due to the incomplete longitudinal data are imputed using a low-rank matrix completion method. Finally, based on the completed feature matrix, we build a multi-kernel support vector machine (mkSVM) to predict the diagnostic label of samples with unknown diagnostic statuses. Our evaluation indicates that a diagnosis accuracy as high as 78.2% can be achieved when information from the longitudinal scans is used – 6.6% higher than the case using only the reference time point image. In other words, information provided by the longitudinal history of the disease improves diagnosis accuracy

Longitudinal clinical score prediction in Alzheimer's disease with soft-split sparse regression based random forest

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease and affects a large population in the world. Cognitive scores at multiple time points can be reliably used to evaluate the progression of the disease clinically. In recent studies, machine learning techniques have shown promising results on the prediction of AD clinical scores. However, there are multiple limitations in the current models such as linearity assumption and missing data exclusion. Here, we present a nonlinear supervised sparse regression–based random forest (RF) framework to predict a variety of longitudinal AD clinical scores. Furthermore, we propose a soft-split technique to assign probabilistic paths to a test sample in RF for more accurate predictions. In order to benefit from the longitudinal scores in the study, unlike the previous studies that often removed the subjects with missing scores, we first estimate those missing scores with our proposed soft-split sparse regression–based RF and then utilize those estimated longitudinal scores at all the previous time points to predict the scores at the next time point. The experiment results demonstrate that our proposed method is superior to the traditional RF and outperforms other state-of-art regression models. Our method can also be extended to be a general regression framework to predict other disease scores

A transversal approach for patch-based label fusion via matrix completion

Recently, multi-atlas patch-based label fusion has received an increasing interest in the medical image segmentation field. After warping the anatomical labels from the atlas images to the target image by registration, label fusion is the key step to determine the latent label for each target image point. Two popular types of patch-based label fusion approaches are (1) reconstruction-based approaches that compute the target labels as a weighted average of atlas labels, where the weights are derived by reconstructing the target image patch using the atlas image patches; and (2) classification-based approaches that determine the target label as a mapping of the target image patch, where the mapping function is often learned using the atlas image patches and their corresponding labels. Both approaches have their advantages and limitations. In this paper, we propose a novel patch-based label fusion method to combine the above two types of approaches via matrix completion (and hence, we call it transversal). As we will show, our method overcomes the individual limitations of both reconstruction-based and classification-based approaches. Since the labeling confidences may vary across the target image points, we further propose a sequential labeling framework that first labels the highly confident points and then gradually labels more challenging points in an iterative manner, guided by the label information determined in the previous iterations. We demonstrate the performance of our novel label fusion method in segmenting the hippocampus in the ADNI dataset, subcortical and limbic structures in the LONI dataset, and mid-brain structures in the SATA dataset. We achieve more accurate segmentation results than both reconstruction-based and classification-based approaches. Our label fusion method is also ranked 1st in the online SATA Multi-Atlas Segmentation Challenge

A Robust Deep Model for Improved Classification of AD/MCI Patients

Accurate classification of Alzheimer\u27s disease (AD) and its prodromal stage, mild cognitive impairment (MCI), plays a critical role in possibly preventing progression of memory impairment and improving quality of life for AD patients. Among many research tasks, it is of a particular interest to identify noninvasive imaging biomarkers for AD diagnosis. In this paper, we present a robust deep learning system to identify different progression stages of AD patients based on MRI and PET scans. We utilized the dropout technique to improve classical deep learning by preventing its weight coadaptation, which is a typical cause of overfitting in deep learning. In addition, we incorporated stability selection, an adaptive learning factor, and a multitask learning strategy into the deep learning framework. We applied the proposed method to the ADNI dataset, and conducted experiments for AD and MCI conversion diagnosis. Experimental results showed that the dropout technique is very effective in AD diagnosis, improving the classification accuracies by 5.9% on average as compared to the classical deep learning methods

Multi-Task Linear Programming Discriminant Analysis for the Identification of Progressive MCI Individuals

Accurately identifying mild cognitive impairment (MCI) individuals who will progress to Alzheimer's disease (AD) is very important for making early interventions. Many classification methods focus on integrating multiple imaging modalities such as magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). However, the main challenge for MCI classification using multiple imaging modalities is the existence of a lot of missing data in many subjects. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, almost half of the subjects do not have PET images. In this paper, we propose a new and flexible binary classification method, namely Multi-task Linear Programming Discriminant (MLPD) analysis, for the incomplete multi-source feature learning. Specifically, we decompose the classification problem into different classification tasks, i.e., one for each combination of available data sources. To solve all different classification tasks jointly, our proposed MLPD method links them together by constraining them to achieve the similar estimated mean difference between the two classes (under classification) for those shared features. Compared with the state-of-the-art incomplete Multi-Source Feature (iMSF) learning method, instead of constraining different classification tasks to choose a common feature subset for those shared features, MLPD can flexibly and adaptively choose different feature subsets for different classification tasks. Furthermore, our proposed MLPD method can be efficiently implemented by linear programming. To validate our MLPD method, we perform experiments on the ADNI baseline dataset with the incomplete MRI and PET images from 167 progressive MCI (pMCI) subjects and 226 stable MCI (sMCI) subjects. We further compared our method with the iMSF method (using incomplete MRI and PET images) and also the single-task classification method (using only MRI or only subjects with both MRI and PET images). Experimental results show very promising performance of our proposed MLPD method

Neurodegenerative disease diagnosis using incomplete multi-modality data via matrix shrinkage and completion

In this work, we are interested in predicting the diagnostic statuses of potentially neurodegenerated patients using feature values derived from multi-modality neuroimaging data and biological data, which might be incomplete. Collecting the feature values into a matrix, with each row containing a feature vector of a sample, we propose a framework to predict the corresponding associated multiple target outputs (e.g., diagnosis label and clinical scores) from this feature matrix by performing matrix shrinkage following by matrix completion. Specifically, we first combine the feature and target output matrices into a large matrix and then partition this large incomplete matrix into smaller submatrices, each consisting of samples with complete feature values (corresponding to a certain combination of modalities) and target outputs. Treating each target output as the outcome of a prediction task, we apply a 2-step multi-task learning algorithm to select the most discriminative features and samples in each submatrix. Features and samples that are not selected in any of the submatrices are discarded, resulting in a shrunk version of the original large matrix. The missing feature values and unknown target outputs of the shrunk matrix is then completed simultaneously. Experimental results using the ADNI dataset indicate that our proposed framework achieves higher classification accuracy at a greater speed when compared with conventional imputation-based classification methods and also yields competitive performance when compared with the state-of-the-art methods

Robust Feature-Sample Linear Discriminant Analysis for Brain Disorders Diagnosis

Abstract A wide spectrum of discriminative methods is increasingly used in diverse applications for classification or regression tasks. However, many existing discriminative methods assume that the input data is nearly noise-free, which limits their applications to solve real-world problems. Particularly for disease diagnosis, the data acquired by the neuroimaging devices are always prone to different sources of noise. Robust discriminative models are somewhat scarce and only a few attempts have been made to make them robust against noise or outliers. These methods focus on detecting either the sample-outliers or feature-noises. Moreover, they usually use unsupervised de-noising procedures, or separately de-noise the training and the testing data. All these factors may induce biases in the learning process, and thus limit its performance. In this paper, we propose a classification method based on the least-squares formulation of linear discriminant analysis, which simultaneously detects the sample-outliers and feature-noises. The proposed method operates under a semi-supervised setting, in which both labeled training and unlabeled testing data are incorporated to form the intrinsic geometry of the sample space. Therefore, the violating samples or feature values are identified as sample-outliers or feature-noises, respectively. We test our algorithm on one synthetic and two brain neurodegenerative databases (particularly for Parkinson's disease and Alzheimer's disease). The results demonstrate that our method outperforms all baseline and state-of-the-art methods, in terms of both accuracy and the area under the ROC curve

Identification of infants at high-risk for autism spectrum disorder using multiparameter multiscale white matter connectivity networks: Identification of Infants at High-Risk for ASD

Autism spectrum disorder (ASD) is a wide range of disabilities that cause life-long cognitive impairment and social, communication, and behavioral challenges. Early diagnosis and medical intervention are important for improving the life quality of autistic patients. However, in the current practice, diagnosis often has to be delayed until the behavioral symptoms become evident during childhood. In this study, we demonstrate the feasibility of using machine learning techniques for identifying high-risk ASD infants at as early as six months after birth. This is based on the observation that ASD-induced abnormalities in white matter (WM) tracts and whole-brain connectivity have already started to appear within 24 months after birth. In particular, we propose a novel multikernel support vector machine classification framework by using the connectivity features gathered from WM connectivity networks, which are generated via multiscale regions of interest (ROIs) and multiple diffusion statistics such as fractional anisotropy, mean diffusivity, and average fiber length. Our proposed framework achieves an accuracy of 76% and an area of 0.80 under the receiver operating characteristic curve (AUC), in comparison to the accuracy of 70% and the AUC of 70% provided by the best single-parameter single-scale network. The improvement in accuracy is mainly due to the complementary information provided by multiparameter multiscale networks. In addition, our framework also provides the potential imaging connectomic markers and an objective means for early ASD diagnosis