Deep Learning for Multiclass Classification, Predictive Modeling and Segmentation of Disease Prone Regions in Alzheimer’s Disease

One of the challenges facing accurate diagnosis and prognosis of Alzheimer’s Disease (AD) is identifying the subtle changes that define the early onset of the disease. This dissertation investigates three of the main challenges confronted when such subtle changes are to be identified in the most meaningful way. These are (1) the missing data challenge, (2) longitudinal modeling of disease progression, and (3) the segmentation and volumetric calculation of disease-prone brain areas in medical images. The scarcity of sufficient data compounded by the missing data challenge in many longitudinal samples exacerbates the problem as we seek statistical meaningfulness in multiclass classification and regression analysis. Although there are many participants in the AD Neuroimaging Initiative (ADNI) study, many of the observations have a lot of missing features which often lead to the exclusion of potentially valuable data points that could add significant meaning in many ongoing experiments. Motivated by the necessity of examining all participants, even those with missing tests or imaging modalities, multiple techniques of handling missing data in this domain have been explored. Specific attention was drawn to the Gradient Boosting (GB) algorithm which has an inherent capability of addressing missing values. Prior to applying state-of-the-art classifiers such as Support Vector Machine (SVM) and Random Forest (RF), the impact of imputing data in common datasets with numerical techniques has been also investigated and compared with the GB algorithm. Furthermore, to discriminate AD subjects from healthy control individuals, and Mild Cognitive Impairment (MCI), longitudinal multimodal heterogeneous data was modeled using recurring neural networks (RNNs). In the segmentation and volumetric calculation challenge, this dissertation places its focus on one of the most relevant disease-prone areas in many neurological and neurodegenerative diseases, the hippocampus region. Changes in hippocampus shape and volume are considered significant biomarkers for AD diagnosis and prognosis. Thus, a two-stage model based on integrating the Vision Transformer and Convolutional Neural Network (CNN) is developed to automatically locate, segment, and estimate the hippocampus volume from the brain 3D MRI. The proposed architecture was trained and tested on a dataset containing 195 brain MRIs from the 2019 Medical Segmentation Decathlon Challenge against the manually segmented regions provided therein and was deployed on 326 MRI from our own data collected through Mount Sinai Medical Center as part of the 1Florida Alzheimer Disease Research Center (ADRC)

A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.Comment: Revised survey includes expanded discussion section and reworked introductory section on common deep architectures. Added missed papers from before Feb 1st 201

A CAD system for early diagnosis of autism using different imaging modalities.

The term “autism spectrum disorder” (ASD) refers to a collection of neuro-developmental disorders that affect linguistic, behavioral, and social skills. Autism has many symptoms, most prominently, social impairment and repetitive behaviors. It is crucial to diagnose autism at an early stage for better assessment and investigation of this complex syndrome. There have been a lot of efforts to diagnose ASD using different techniques, such as imaging modalities, genetic techniques, and behavior reports. Imaging modalities have been extensively exploited for ASD diagnosis, and one of the most successful ones is Magnetic resonance imaging(MRI),where it has shown promise for the early diagnosis of the ASD related abnormalities in particular. Magnetic resonance imaging (MRI) modalities have emerged as powerful means that facilitate non-invasive clinical diagnostics of various diseases and abnormalities since their inception in the 1980s. After the advent in the nineteen eighties, MRI soon became one of the most promising non- invasive modalities for visualization and diagnostics of ASD-related abnormalities. Along with its main advantage of no exposure to radiation, high contrast, and spatial resolution, the recent advances to MRI modalities have notably increased diagnostic certainty. Multiple MRI modalities, such as different types of structural MRI (sMRI) that examines anatomical changes, and functional MRI (fMRI) that examines brain activity by monitoring blood flow changes,have been employed to investigate facets of ASD in order to better understand this complex syndrome. This work aims at developing a new computer-aided diagnostic (CAD) system for autism diagnosis using different imaging modalities. It mainly relies on making use of structural magnetic resonance images for extracting notable shape features from parts of the brainthat proved to correlate with ASD from previous neuropathological studies. Shape features from both the cerebral cortex (Cx) and cerebral white matter(CWM)are extracted. Fusion of features from these two structures is conducted based on the recent findings suggesting that Cx changes in autism are related to CWM abnormalities. Also, when fusing features from more than one structure, this would increase the robustness of the CAD system. Moreover, fMRI experiments are done and analyzed to find areas of activation in the brains of autistic and typically developing individuals that are related to a specific task. All sMRI findings are fused with those of fMRI to better understand ASD in terms of both anatomy and functionality,and thus better classify the two groups. This is one aspect of the novelty of this CAD system, where sMRI and fMRI studies are both applied on subjects from different ages to diagnose ASD. In order to build such a CAD system, three main blocks are required. First, 3D brain segmentation is applied using a novel hybrid model that combines shape, intensity, and spatial information. Second, shape features from both Cx and CWM are extracted and anf MRI reward experiment is conducted from which areas of activation that are related to the task of this experiment are identified. Those features were extracted from local areas of the brain to provide an accurate analysis of ASD and correlate it with certain anatomical areas. Third and last, fusion of all the extracted features is done using a deep-fusion classification network to perform classification and obtain the diagnosis report. Fusing features from all modalities achieved a classification accuracy of 94.7%, which emphasizes the significance of combining structures/modalities for ASD diagnosis. To conclude, this work could pave the pathway for better understanding of the autism spectrum by finding local areas that correlate to the disease. The idea of personalized medicine is emphasized in this work, where the proposed CAD system holds the promise to resolve autism endophenotypes and help clinicians deliver personalized treatment to individuals affected with this complex syndrome

Precis of neuroconstructivism: how the brain constructs cognition

Neuroconstructivism: How the Brain Constructs Cognition proposes a unifying framework for the study of cognitive development that brings together (1) constructivism (which views development as the progressive elaboration of increasingly complex structures), (2) cognitive neuroscience (which aims to understand the neural mechanisms underlying behavior), and (3) computational modeling (which proposes formal and explicit specifications of information processing). The guiding principle of our approach is context dependence, within and (in contrast to Marr [1982]) between levels of organization. We propose that three mechanisms guide the emergence of representations: competition, cooperation, and chronotopy; which themselves allow for two central processes: proactivity and progressive specialization. We suggest that the main outcome of development is partial representations, distributed across distinct functional circuits. This framework is derived by examining development at the level of single neurons, brain systems, and whole organisms. We use the terms encellment, embrainment, and embodiment to describe the higher-level contextual influences that act at each of these levels of organization. To illustrate these mechanisms in operation we provide case studies in early visual perception, infant habituation, phonological development, and object representations in infancy. Three further case studies are concerned with interactions between levels of explanation: social development, atypical development and within that, developmental dyslexia. We conclude that cognitive development arises from a dynamic, contextual change in embodied neural structures leading to partial representations across multiple brain regions and timescales, in response to proactively specified physical and social environment

Learning from Complex Neuroimaging Datasets

Advancements in Magnetic Resonance Imaging (MRI) allowed for the early diagnosis of neurodevelopmental disorders and neurodegenerative diseases. Neuroanatomical abnormalities in the cerebral cortex are often investigated by examining group-level differences of brain morphometric measures extracted from highly-sampled cortical surfaces. However, group-level differences do not allow for individual-level outcome prediction critical for the application to clinical practice. Despite the success of MRI-based deep learning frameworks, critical issues have been identified: (1) extracting accurate and reliable local features from the cortical surface, (2) determining a parsimonious subset of cortical features for correct disease diagnosis, (3) learning directly from a non-Euclidean high-dimensional feature space, (4) improving the robustness of multi-task multi-modal models, and (5) identifying anomalies in imbalanced and heterogeneous settings. This dissertation describes novel methodological contributions to tackle the challenges above. First, I introduce a Laplacian-based method for quantifying local Extra-Axial Cerebrospinal Fluid (EA-CSF) from structural MRI. Next, I describe a deep learning approach for combining local EA-CSF with other morphometric cortical measures for early disease detection. Then, I propose a data-driven approach for extending convolutional learning to non-Euclidean manifolds such as cortical surfaces. I also present a unified framework for robust multi-task learning from imaging and non-imaging information. Finally, I propose a semi-supervised generative approach for the detection of samples from untrained classes in imbalanced and heterogeneous developmental datasets. The proposed methodological contributions are evaluated by applying them to the early detection of Autism Spectrum Disorder (ASD) in the first year of the infant’s life. Also, the aging human brain is examined in the context of studying different stages of Alzheimer’s Disease (AD).Doctor of Philosoph