Label-aligned multi-task feature learning for multimodal classification of Alzheimer’s disease and mild cognitive impairment

Multimodal classification methods using different modalities of imaging and non-imaging data have recently shown great advantages over traditional single-modality-based ones for diagnosis and prognosis of Alzheimer’s disease (AD), as well as its prodromal stage, i.e., mild cognitive impairment (MCI). However, to the best of our knowledge, most existing methods focus on mining the relationship across multiple modalities of the same subjects, while ignoring the potentially useful relationship across different subjects. Accordingly, in this paper, we propose a novel learning method for multimodal classification of AD/MCI, by fully exploring the relationships across both modalities and subjects. Specifically, our proposed method includes two subsequent components, i.e., label-aligned multi-task feature selection and multimodal classification. In the first step, the feature selection learning from multiple modalities are treated as different learning tasks and a group sparsity regularizer is imposed to jointly select a subset of relevant features. Furthermore, to utilize the discriminative information among labeled subjects, a new label-aligned regularization term is added into the objective function of standard multi-task feature selection, where label-alignment means that all multi-modality subjects with the same class labels should be closer in the new feature-reduced space. In the second step, a multi-kernel support vector machine (SVM) is adopted to fuse the selected features from multi-modality data for final classification. To validate our method, we perform experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline MRI and FDG-PET imaging data. The experimental results demonstrate that our proposed method achieves better classification performance compared with several state-of-the-art methods for multimodal classification of AD/MCI

Sparse Multi-Response Tensor Regression for Alzheimer's Disease Study With Multivariate Clinical Assessments

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has recently seen serious increase in the number of affected subjects. In the last decade, neuroimaging has been shown to be a useful tool to understand AD and its prodromal stage, amnestic mild cognitive impairment (MCI). The majority of AD/MCI studies have focused on disease diagnosis, by formulating the problem as classification with a binary outcome of AD/MCI or healthy controls. There have recently emerged studies that associate image scans with continuous clinical scores that are expected to contain richer information than a binary outcome. However, very few studies aim at modeling multiple clinical scores simultaneously, even though it is commonly conceived that multivariate outcomes provide correlated and complementary information about the disease pathology. In this article, we propose a sparse multi-response tensor regression method to model multiple outcomes jointly as well as to model multiple voxels of an image jointly. The proposed method is particularly useful to both infer clinical scores and thus disease diagnosis, and to identify brain subregions that are highly relevant to the disease outcomes. We conducted experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and showed that the proposed method enhances the performance and clearly outperforms the competing solutions

An Intelligent Hybrid Optimization with Deep Learning model-based Schizophrenia Identification from Structural MRI

One of the fatal diseases that claim women while they are pregnant or nursing is schizophrenia. Despite several developments and symptoms, it can be challenging to discern between benign and malignant conditions. The main and most popular imaging method to predict Schizophrenia is MR Images. Furthermore, a few earlier models had a definite accuracy when diagnosing the condition. Stable MRI criteria must also be implemented immediately. Compared to other imaging technologies, the MRI imaging method is the simplest, safest, and most common for predicting Schizophrenia. The following factors are mostly involved in the subprocess for the initial MRI image. Before calculating the length between the sample point and the cluster center, the initial cluster center of the sample is identified. Classification is done according to how far the sample point is from the cluster center. The picture is then generated once the new cluster center has been derived using the classification history and verified to match the cluster convergence condition. A grey wolf optimization-based convolutional neural network approach is offered to get beyond the limitations and find schizophrenia, whether its hazardous or not. Many MRI images or datasets are analyzed in a short time, and the results show a more accurate or higher rate of schizophrenia recognition

Fine-Granularity Functional Interaction Signatures for Characterization of Brain Conditions

In the human brain, functional activity occurs at multiple spatial scales. Current studies on functional brain networks and their alterations in brain diseases via resting-state functional magnetic resonance imaging (rs-fMRI) are generally either at local scale (regionally confined analysis and inter-regional functional connectivity analysis) or at global scale (graph theoretic analysis). In contrast, inferring functional interaction at fine-granularity sub-network scale has not been adequately explored yet. Here our hypothesis is that functional interaction measured at fine-granularity subnetwork scale can provide new insight into the neural mechanisms of neurological and psychological conditions, thus offering complementary information for healthy and diseased population classification. In this paper, we derived fine-granularity functional interaction (FGFI) signatures in subjects with Mild Cognitive Impairment (MCI) and Schizophrenia by diffusion tensor imaging (DTI) and rsfMRI, and used patient-control classification experiments to evaluate the distinctiveness of the derived FGFI features. Our experimental results have shown that the FGFI features alone can achieve comparable classification performance compared with the commonly used inter-regional connectivity features. However, the classification performance can be substantially improved when FGFI features and inter-regional connectivity features are integrated, suggesting the complementary information achieved from the FGFI signatures

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease

Background: Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Methods: Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. Results: The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. Conclusions: In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics

An insight into the brain of patients with type-2 diabetes mellitus and impaired glucose tolerance using multi-modal magnetic resonance image processing

The purpose of this thesis was to investigate brain anatomy and physiology of subjects with impaired glucose tolerance (IGT - 12 subjects), type-2 diabetes (T2DM - 17 subjects) and normoglycemia (16 subjects) using multi-modal magnetic resonance imaging (MRI) at 3T. Perfusion imaging using quantitative STAR labeling of arterial regions (QUASAR) arterial spin labeling (ASL) was the core dataset. Optimization of the post-processing methodology for this sequence was performed and the outcome was used for hemodynamic analysis of the cohort. Typical perfusion-related parameters, along with novel hemodynamic features were quantified. High-resolution structural, angiographic and carotid flow scans were also acquired and processed. Functional acquisitions were repeated following a vasodilating stimulus. Differences between the groups were examined using statistical analysis and a machine-learning framework. Hemodynamic parameters differing between the groups emerged from both baseline and post-stimulus scans for T2DM and mainly from the post-stimulus scan for IGT. It was demonstrated that quantification of not-typically determined hemodynamic features could lead to optimal group-separation. Such features captured the pattern of delayed delivery of the blood to the arterial and tissue compartments of the hyperglycemic groups. Alterations in gray and white matter, cerebral vasculature and carotid blood flow were detected for the T2DM group. The IGT cohort was structurally similar to the healthy cohort but demonstrated functional similarities to T2DM. When combining all extracted MRI metrics, features driving optimal separation between different glycemic conditions emerged mainly from the QUASAR scan. The only highly discriminant non-QUASAR feature, when comparing T2DM to healthy subjects, emerged from the cerebral angiogram. In this thesis, it was demonstrated that MRI-derived features could lead to potentially optimal differentiation between normoglycemia and hyperglycemia. More importantly, it was shown that an impaired cerebral hemodynamic pattern exists in both IGT and T2DM and that the IGT group exhibits functional alterations similar to the T2DM group

Radiomic Features to Predict Overall Survival Time for Patients with Glioblastoma Brain Tumors Based on Machine Learning and Deep Learning Methods

Machine Learning (ML) methods including Deep Learning (DL) Methods have been employed in the medical field to improve diagnosis process and patient’s prognosis outcomes. Glioblastoma multiforme is an extremely aggressive Glioma brain tumor that has a poor survival rate. Understanding the behavior of the Glioblastoma brain tumor is still uncertain and some factors are still unrecognized. In fact, the tumor behavior is important to decide a proper treatment plan and to improve a patient’s health. The aim of this dissertation is to develop a Computer-Aided-Diagnosis system (CADiag) based on ML/DL methods to automatically estimate the Overall Survival Time (OST) for patients with Glioblastoma brain tumors from medical imaging and non-imaging data. This system is developed to enhance and speed-up the diagnosis process, as well as to increase understanding of the behavior of Glioblastoma brain tumors. The proposed OST prediction system is developed based on a classification process to categorize a GBM patient into one of the following three survival time groups: short-term (months), mid-term (10-15 months), and long-term (\u3e15 months). The Brain Tumor Segmentation challenge (BraTS) dataset is used to develop the automatic OST prediction system. This dataset consists of multimodal preoperative Magnetic Resonance Imaging (mpMRI) data, and clinical data. The training data is relatively small in size to train an accurate OST prediction model based on DL method. Therefore, traditional ML methods such as Support Vector Machine (SVM), Neural Network, K-Nearest Neighbor (KNN), Decision Tree (DT) were used to develop the OST prediction model for GBM patients. The main contributions in the perspective of ML field include: developing and evaluating five novel radiomic feature extraction methods to produce an automatic and reliable OST prediction system based on classification task. These methods are volumetric, shape, location, texture, histogram-based, and DL features. Some of these radiomic features can be extracted directly from MRI images, such as statistical texture features and histogram-based features. However, preprocessing methods are required to extract automatically other radiomic features from MRI images such as the volume, shape, and location information of the GBM brain tumors. Therefore, a three-dimension (3D) segmentation DL model based on modified U-Net architecture is developed to identify and localize the three glioma brain tumor subregions, peritumoral edematous/invaded tissue (ED), GD-enhancing tumor (ET), and the necrotic tumor core (NCR), in multi MRI scans. The segmentation results are used to calculate the volume, location and shape information of a GBM tumor. Two novel approaches based on volumetric, shape, and location information, are proposed and evaluated in this dissertation. To improve the performance of the OST prediction system, information fusion strategies based on data-fusion, features-fusion and decision-fusion are involved. The best prediction model was developed based on feature fusions and ensemble models using NN classifiers. The proposed OST prediction system achieved competitive results in the BraTS 2020 with accuracy 55.2% and 55.1% on the BraTS 2020 validation and test datasets, respectively. In sum, developing automatic CADiag systems based on robust features and ML methods, such as our developed OST prediction system, enhances the diagnosis process in terms of cost, accuracy, and time. Our OST prediction system was evaluated from the perspective of the ML field. In addition, preprocessing steps are essential to improve not only the quality of the features but also boost the performance of the prediction system. To test the effectiveness of our developed OST system in medical decisions, we suggest more evaluations from the perspective of biology and medical decisions, to be then involved in the diagnosis process as a fast, inexpensive and automatic diagnosis method. To improve the performance of our developed OST prediction system, we believe it is required to increase the size of the training data, involve multi-modal data, and/or provide any uncertain or missing information to the data (such as patients\u27 resection statuses, gender, etc.). The DL structure is able to extract numerous meaningful low-level and high-level radiomic features during the training process without any feature type nominations by researchers. We thus believe that DL methods could achieve better predictions than ML methods if large size and proper data is available

The anthropometric, environmental and genetic determinants of right ventricular structure and function

BACKGROUND Measures of right ventricular (RV) structure and function have significant prognostic value. The right ventricle is currently assessed by global measures, or point surrogates, which are insensitive to regional and directional changes. We aim to create a high-resolution three-dimensional RV model to improve understanding of its structural and functional determinants. These may be particularly of interest in pulmonary hypertension (PH), a condition in which RV function and outcome are strongly linked. PURPOSE To investigate the feasibility and additional benefit of applying three-dimensional phenotyping and contemporary statistical and genetic approaches to large patient populations. METHODS Healthy subjects and incident PH patients were prospectively recruited. Using a semi-automated atlas-based segmentation algorithm, 3D models characterising RV wall position and displacement were developed, validated and compared with anthropometric, physiological and genetic influences. Statistical techniques were adapted from other high-dimensional approaches to deal with the problems of multiple testing, contiguity, sparsity and computational burden. RESULTS 1527 healthy subjects successfully completed high-resolution 3D CMR and automated segmentation. Of these, 927 subjects underwent next-generation sequencing of the sarcomeric gene titin and 947 subjects completed genotyping of common variants for genome-wide association study. 405 incident PH patients were recruited, of whom 256 completed phenotyping. 3D modelling demonstrated significant reductions in sample size compared to two-dimensional approaches. 3D analysis demonstrated that RV basal-freewall function reflects global functional changes most accurately and that a similar region in PH patients provides stronger survival prediction than all anthropometric, haemodynamic and functional markers. Vascular stiffness, titin truncating variants and common variants may also contribute to changes in RV structure and function. CONCLUSIONS High-resolution phenotyping coupled with computational analysis methods can improve insights into the determinants of RV structure and function in both healthy subjects and PH patients. Large, population-based approaches offer physiological insights relevant to clinical care in selected patient groups.Open Acces

Role of Anterior Cingulate Cortex in Saccade Control

Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. It has been postulated that prefrontal cortex is mainly involved in higher order cognitive functions. Specifically, anterior cingulate cortex (ACC), which is part of the prefrontal cortex, is suggested to be involved in performance monitoring and conflict monitoring that are considered to be cognitive control functions. Saccades are the fast eye movements that align the fovea on the objects of interest in the environment. In this thesis, I have explored the role of ACC in control of saccadic eye movements. First, I performed a resting-state fMRI study to identify areas within the ACC that are functionally connected to the frontal eye fields (FEF). It has been shown that FEF is involved in saccade generation. Therefore, the ACC areas that are functionally connected to FEF could be hypothesized to have a role in saccade control. Then, I performed simultaneous electrophysiological recordings in the ACC and FEF. Furthermore, I explored whether ACC exerts control over FEF. My results show that ACC is involved in cognitive control of saccades. Furthermore, the ACC and FEF neurons communicate through synchronized theta and beta band activity in these areas. The results of this thesis shine light on the mechanisms by which these brain areas communicate. Moreover, my findings support the notion that ACC and FEF have a unique oscillatory property, and more specifically ACC has a prominent theta band, and to a lesser extent beta band activity