A distributed multitask multimodal approach for the prediction of Alzheimer's disease in a longitudinal study.

Predicting the progression of Alzheimer's Disease (AD) has been held back for decades due to the lack of sufficient longitudinal data required for the development of novel machine learning algorithms. This study proposes a novel machine learning algorithm for predicting the progression of Alzheimer's disease using a distributed multimodal, multitask learning method. More specifically, each individual task is defined as a regression model, which predicts cognitive scores at a single time point. Since the prediction tasks for multiple intervals are related to each other in chronological order, multitask regression models have been developed to track the relationship between subsequent tasks. Furthermore, since subjects have various combinations of recording modalities together with other genetic, neuropsychological and demographic risk factors, special attention is given to the fact that each modality may experience a specific sparsity pattern. The model is hence generalized by exploiting multiple individual multitask regression coefficient matrices for each modality. The outcome for each independent modality-specific learner is then integrated with complementary information, known as risk factor parameters, revealing the most prevalent trends of the multimodal data. This new feature space is then used as input to the gradient boosting kernel in search for a more accurate prediction. This proposed model not only captures the complex relationships between the different feature representations, but it also ignores any unrelated information which might skew the regression coefficients. Comparative assessments are made between the performance of the proposed method with several other well-established methods using different multimodal platforms. The results indicate that by capturing the interrelatedness between the different modalities and extracting only relevant information in the data, even in an incomplete longitudinal dataset, will yield minimized prediction errors.

A unique color-coded visualization system with multimodal information fusion and deep learning in a longitudinal study of Alzheimer's disease.

PURPOSE: Automated diagnosis and prognosis of Alzheimer's Disease remain a challenging problem that machine learning (ML) techniques have attempted to resolve in the last decade. This study introduces a first-of-its-kind color-coded visualization mechanism driven by an integrated ML model to predict disease trajectory in a 2-year longitudinal study. The main aim of this study is to help capture visually in 2D and 3D renderings the diagnosis and prognosis of AD, therefore augmenting our understanding of the processes of multiclass classification and regression analysis. METHOD: The proposed method, Machine Learning for Visualizing AD (ML4VisAD), is designed to predict disease progression through a visual output. This newly developed model takes baseline measurements as input to generate a color-coded visual image that reflects disease progression at different time points. The architecture of the network relies on convolutional neural networks. With 1123 subjects selected from the ADNI QT-PAD dataset, we use a 10-fold cross-validation process to evaluate the method. Multimodal inputs* include neuroimaging data (MRI, PET), neuropsychological test scores (excluding MMSE, CDR-SB, and ADAS to avoid bias), cerebrospinal fluid (CSF) biomarkers with measures of amyloid beta (ABETA), phosphorylated tau protein (PTAU), total tau protein (TAU), and risk factors that include age, gender, years of education, and ApoE4 gene. FINDINGS/RESULTS: Based on subjective scores reached by three raters, the results showed an accuracy of 0.82 ± 0.03 for a 3-way classification and 0.68 ± 0.05 for a 5-way classification. The visual renderings were generated in 0.08 msec for a 23 × 23 output image and in 0.17 ms for a 45 × 45 output image. Through visualization, this study (1) demonstrates that the ML visual output augments the prospects for a more accurate diagnosis and (2) highlights why multiclass classification and regression analysis are incredibly challenging. An online survey was conducted to gauge this visualization platform's merits and obtain valuable feedback from users. All implementation codes are shared online on GitHub. CONCLUSION: This approach makes it possible to visualize the many nuances that lead to a specific classification or prediction in the disease trajectory, all in context to multimodal measurements taken at baseline. This ML model can serve as a multiclass classification and prediction model while reinforcing the diagnosis and prognosis capabilities by including a visualization platform.

Addressing the missing data challenge in multi-modal datasets for the diagnosis of Alzheimer's disease.

BACKGROUND: One of the challenges facing accurate diagnosis and prognosis of Alzheimer's disease, beyond identifying the subtle changes that define its early onset, is the scarcity of sufficient data compounded by the missing data challenge. Although there are many participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, many of the observations have a lot of missing features which often leads to the exclusion of potentially valuable data points in many ongoing experiments, especially in longitudinal studies. NEW METHODS: Motivated by the necessity of examining all participants, even those with missing tests or imaging modalities, this study draws attention to the Gradient Boosting (GB) algorithm which has an inherent capability of addressing missing values. The four groups considered include: Cognitively Normal (CN), Early Mild Cognitive Impairment (EMCI), Late Mild Cognitive Impairment (LMCI) and Alzheimer's Disease (AD). Prior to applying state of the art classifiers such as Support Vector Machine (SVM) and Random Forest (RF), the impact of imputing (i.e., replacing) data in common datasets with numerical techniques has been investigated and compared with the GB algorithm. Empirical evaluations show that the GB performance is highly resilient to missing values in comparison to SVM and RF algorithms. These latter algorithms can however be improved when coupled with more sophisticated imputation technique such as soft-impute or K-Nearest Neighbors (KNN) algorithm assuming low extent of data incompleteness. RESULTS: The classification accuracy has been improved by up to 3% in the multiclass classification of all four classes of subjects when all the samples including the incomplete ones are considered during the model generation and testing phases. COMPARISON WITH EXISTING METHODS: Unlike other methods, the proposed approach addresses the challenging multiclass classification of the ADNI dataset in the presence of different levels of missing data points. It also provides a comparative study on effects of existing imputation techniques on a block-wise missing data. Results of the proposed method are validated against gold standard methods used for AD classification.

A Tensorized Multitask Deep Learning Network for Progression Prediction of Alzheimer's Disease.

With the advances in machine learning for the diagnosis of Alzheimer's disease (AD), most studies have focused on either identifying the subject's status through classification algorithms or on predicting their cognitive scores through regression methods, neglecting the potential association between these two tasks. Motivated by the need to enhance the prospects for early diagnosis along with the ability to predict future disease states, this study proposes a deep neural network based on modality fusion, kernelization, and tensorization that perform multiclass classification and longitudinal regression simultaneously within a unified multitask framework. This relationship between multiclass classification and longitudinal regression is found to boost the efficacy of the final model in dealing with both tasks. Different multimodality scenarios are investigated, and complementary aspects of the multimodal features are exploited to simultaneously delineate the subject's label and predict related cognitive scores at future timepoints using baseline data. The main intent in this multitask framework is to consolidate the highest accuracy possible in terms of precision, sensitivity, F1 score, and area under the curve (AUC) in the multiclass classification task while maintaining the highest similarity in the MMSE score as measured through the correlation coefficient and the RMSE for all time points under the prediction task, with both tasks, run simultaneously under the same set of hyperparameters. The overall accuracy for multiclass classification of the proposed KTMnet method is 66.85 ± 3.77. The prediction results show an average RMSE of 2.32 ± 0.52 and a correlation of 0.71 ± 5.98 for predicting MMSE throughout the time points. These results are compared to state-of-the-art techniques reported in the literature. A discovery from the multitasking of this consolidated machine learning framework is that a set of hyperparameters that optimize the prediction results may not necessarily be the same as those that would optimize the multiclass classification. In other words, there is a breakpoint beyond which enhancing further the results of one process could lead to the downgrading in accuracy for the other.

PET Imaging of Tau Pathology and Amyloid-ß, and MRI for Alzheimer's Disease Feature Fusion and Multimodal Classification.

BACKGROUND: Machine learning is a promising tool for biomarker-based diagnosis of Alzheimer's disease (AD). Performing multimodal feature selection and studying the interaction between biological and clinical AD can help to improve the performance of the diagnosis models. OBJECTIVE: This study aims to formulate a feature ranking metric based on the mutual information index to assess the relevance and redundancy of regional biomarkers and improve the AD classification accuracy. METHODS: From the Alzheimer's Disease Neuroimaging Initiative (ADNI), 722 participants with three modalities, including florbetapir-PET, flortaucipir-PET, and MRI, were studied. The multivariate mutual information metric was utilized to capture the redundancy and complementarity of the predictors and develop a feature ranking approach. This was followed by evaluating the capability of single-modal and multimodal biomarkers in predicting the cognitive stage. RESULTS: Although amyloid-ß deposition is an earlier event in the disease trajectory, tau PET with feature selection yielded a higher early-stage classification F1-score (65.4%) compared to amyloid-ß PET (63.3%) and MRI (63.2%). The SVC multimodal scenario with feature selection improved the F1-score to 70.0% and 71.8% for the early and late-stage, respectively. When age and risk factors were included, the scores improved by 2 to 4%. The Amyloid-Tau-Neurodegeneration [AT(N)] framework helped to interpret the classification results for different biomarker categories. CONCLUSION: The results underscore the utility of a novel feature selection approach to reduce the dimensionality of multimodal datasets and enhance model performance. The AT(N) biomarker framework can help to explore the misclassified cases by revealing the relationship between neuropathological biomarkers and cognition.

Image-to-Images Translation for Multi-Task Organ Segmentation and Bone Suppression in Chest X-Ray Radiography.

Chest X-ray radiography is one of the earliest medical imaging technologies and remains one of the most widely-used for diagnosis, screening, and treatment follow up of diseases related to lungs and heart. The literature in this field of research reports many interesting studies dealing with the challenging tasks of bone suppression and organ segmentation but performed separately, limiting any learning that comes with the consolidation of parameters that could optimize both processes. This study, and for the first time, introduces a multitask deep learning model that generates simultaneously the bone-suppressed image and the organ-segmented image, enhancing the accuracy of tasks, minimizing the number of parameters needed by the model and optimizing the processing time, all by exploiting the interplay between the network parameters to benefit the performance of both tasks. The architectural design of this model, which relies on a conditional generative adversarial network, reveals the process on how the wellestablished pix2pix network (image-to-image network) is modified to fit the need for multitasking and extending it to the new image-to-images architecture. The developed source code of this multitask model is shared publicly on Github as the first attempt for providing the two-task pix2pix extension, a supervised/paired/aligned/registered image-to-images translation which would be useful in many multitask applications. Dilated convolutions are also used to improve the results through a more effective receptive field assessment. The comparison with state-of-the-art al-gorithms along with ablation study and a demonstration video1 are provided to evaluate the efficacy and gauge the merits of the proposed approach.