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

A novel diffusion tensor imaging-based computer-aided diagnostic system for early diagnosis of autism.

Autism spectrum disorders (ASDs) denote a significant growing public health concern. Currently, one in 68 children has been diagnosed with ASDs in the United States, and most children are diagnosed after the age of four, despite the fact that ASDs can be identified as early as age two. The ultimate goal of this thesis is to develop a computer-aided diagnosis (CAD) system for the accurate and early diagnosis of ASDs using diffusion tensor imaging (DTI). This CAD system consists of three main steps. First, the brain tissues are segmented based on three image descriptors: a visual appearance model that has the ability to model a large dimensional feature space, a shape model that is adapted during the segmentation process using first- and second-order visual appearance features, and a spatially invariant second-order homogeneity descriptor. Secondly, discriminatory features are extracted from the segmented brains. Cortex shape variability is assessed using shape construction methods, and white matter integrity is further examined through connectivity analysis. Finally, the diagnostic capabilities of these extracted features are investigated. The accuracy of the presented CAD system has been tested on 25 infants with a high risk of developing ASDs. The preliminary diagnostic results are promising in identifying autistic from control patients

The role of MRI in diagnosing autism: a machine learning perspective.

There is approximately 1 in every 44 children in the United States suffers from autism spectrum disorder (ASD), a disorder characterized by social and behavioral impairments. Communication difficulties, interpersonal difficulties, and behavioral difficulties are the top common symptoms. Even though symptoms can begin as early as infancy, it may take multiple visits to a pediatric specialist before an accurate diagnosis can be made. In addition, the diagnosis can be subjective, and different specialists may give different scores. There is a growing body of research suggesting differences in brain development and/or environmental and/or genetic factors contribute to autism development, but scientists have yet to identify exactly the pathology of this disorder. ASD can currently be diagnosed by a set of diagnostic evaluations, regarded as the gold standard, such as the Autism Diagnostic Observation Schedule (ADOS) or the Autism Diagnostic Interview-Revised (ADI-R). A team of qualified clinicians is needed for performing the behavioral and communication tests as well as clinical history information, hence a considerable amount of time, effort, and subjective judgment is involved in using these gold-standard diagnostic instruments. In addition to standard observational assessment, recent advancements in neuroimaging and machine learning suggest a rapid and objective alternative, using brain imaging. An investigation of the employment of different imaging modalities, namely Diffusion Tensor Imaging (DTI), and resting state functional MRI (rs-fMRI) for autism diagnosis is presented in this comprehensive work. A detailed study of the implementation of feature engineering tools to find discriminant insights from different brain imaging modalities, including the use of novel feature representations, and the use of a machine learning framework to assist in the accurate classification of autistic individuals is introduced in this dissertation. Based on three large publicly available datasets, this extensive research highlights different decisions along the pipeline and their impact on diagnostic accuracy. It also identifies potentially impacted brain regions that contribute to an autism diagnosis. Achieving high global state-of-the-art cross-validated accuracy confirms the benefits of feature representation and feature engineering in extracting useful information, as well as the potential benefits of utilizing neuroimaging in the diagnosis of autism. This should enable an early, automated, and more objective personalized diagnosis

Fast and robust hybrid framework for infant brain classification from structural MRI : a case study for early diagnosis of autism.

The ultimate goal of this work is to develop a computer-aided diagnosis (CAD) system for early autism diagnosis from infant structural magnetic resonance imaging (MRI). The vital step to achieve this goal is to get accurate segmentation of the different brain structures: whitematter, graymatter, and cerebrospinal fluid, which will be the main focus of this thesis. The proposed brain classification approach consists of two major steps. First, the brain is extracted based on the integration of a stochastic model that serves to learn the visual appearance of the brain texture, and a geometric model that preserves the brain geometry during the extraction process. Secondly, the brain tissues are segmented based on shape priors, built using a subset of co-aligned training images, that is adapted during the segmentation process using first- and second-order visual appearance features of infant MRIs. The accuracy of the presented segmentation approach has been tested on 300 infant subjects and evaluated blindly on 15 adult subjects. The experimental results have been evaluated by the MICCAI MR Brain Image Segmentation (MRBrainS13) challenge organizers using three metrics: Dice coefficient, 95-percentile Hausdorff distance, and absolute volume difference. The proposed method has been ranked the first in terms of performance and speed

CAD system for early diagnosis of diabetic retinopathy based on 3D extracted imaging markers.

This dissertation makes significant contributions to the field of ophthalmology, addressing the segmentation of retinal layers and the diagnosis of diabetic retinopathy (DR). The first contribution is a novel 3D segmentation approach that leverages the patientspecific anatomy of retinal layers. This approach demonstrates superior accuracy in segmenting all retinal layers from a 3D retinal image compared to current state-of-the-art methods. It also offers enhanced speed, enabling potential clinical applications. The proposed segmentation approach holds great potential for supporting surgical planning and guidance in retinal procedures such as retinal detachment repair or macular hole closure. Surgeons can benefit from the accurate delineation of retinal layers, enabling better understanding of the anatomical structure and more effective surgical interventions. Moreover, real-time guidance systems can be developed to assist surgeons during procedures, improving overall patient outcomes. The second contribution of this dissertation is the introduction of a novel computeraided diagnosis (CAD) system for precise identification of diabetic retinopathy. The CAD system utilizes 3D-OCT imaging and employs an innovative approach that extracts two distinct features: first-order reflectivity and 3D thickness. These features are then fused and used to train and test a neural network classifier. The proposed CAD system exhibits promising results, surpassing other machine learning and deep learning algorithms commonly employed in DR detection. This demonstrates the effectiveness of the comprehensive analysis approach employed by the CAD system, which considers both low-level and high-level data from the 3D retinal layers. The CAD system presents a groundbreaking contribution to the field, as it goes beyond conventional methods, optimizing backpropagated neural networks to integrate multiple levels of information effectively. By achieving superior performance, the proposed CAD system showcases its potential in accurately diagnosing DR and aiding in the prevention of vision loss. In conclusion, this dissertation presents novel approaches for the segmentation of retinal layers and the diagnosis of diabetic retinopathy. The proposed methods exhibit significant improvements in accuracy, speed, and performance compared to existing techniques, opening new avenues for clinical applications and advancements in the field of ophthalmology. By addressing future research directions, such as testing on larger datasets, exploring alternative algorithms, and incorporating user feedback, the proposed methods can be further refined and developed into robust, accurate, and clinically valuable tools for diagnosing and monitoring retinal diseases

Interrogating autism from a multidimensional perspective: an integrative framework.

Autism Spectrum Disorder (ASD) is a condition characterized by social and behavioral impairments, affecting approximately 1 in every 44 children in the United States. Common symptoms include difficulties in communication, interpersonal interactions, and behavior. While symptoms can manifest as early as infancy, obtaining an accurate diagnosis may require multiple visits to a pediatric specialist due to the subjective nature of the assessment, which may yield varying scores from different specialists. Despite growing evidence of the role of differences in brain development and/or environmental and/or genetic factors in autism development, the exact pathology of this disorder has yet to be fully elucidated by scientists. At present, the diagnosis of ASD typically involves a set of gold-standard diagnostic evaluations, such as the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview-Revised (ADI-R), and the more cost-effective Social Responsive Scale (SRS). Administering these diagnostic tests, which involve assessing communication and behavioral patterns, along with obtaining a clinical history, requires the expertise of a team of qualified clinicians. This process is time-consuming, effortful, and involves a degree of subjectivity due to the reliance on clinical judgment. Aside from conventional observational assessments, recent developments in neuroimaging and machine learning offer a fast and objective alternative for diagnosing ASD using brain imaging. This comprehensive work explores the use of different imaging modalvities, namely structural MRI (sMRI) and resting-state functional MRI (rs-fMRI), to investigate their potential for autism diagnosis. The proposed study aims to offer a new approach and perspective in comprehending ASD as a multidimensional problem, within a behavioral space that is defined by one of the available ASD diagnostic tools. This dissertation introduces a thorough investigation of the utilization of feature engineering tools to extract distinctive insights from various brain imaging modalities, including the application of novel feature representations. Additionally, the use of a machine learning framework to aid in the precise classification of individuals with autism is also explored in detail. This extensive research, which draws upon large publicly available datasets, sheds light on the influence of various decisions made throughout the pipeline on diagnostic accuracy. Furthermore, it identifies brain regions that may be impacted and contribute to an autism diagnosis. The attainment of high global state-of-the-art cross-validated, and hold-out set accuracy validates the advantages of feature representation and engineering in extracting valuable information, as well as the potential benefits of employing neuroimaging for autism diagnosis. Furthermore, a suggested diagnostic report has been put forth to assist physicians in mapping diagnoses to underlying neuroimaging markers. This approach could enable an earlier, automated, and more objective personalized diagnosis

Role of machine learning in early diagnosis of kidney diseases.

Machine learning (ML) and deep learning (DL) approaches have been used as indispensable tools in modern artificial intelligence-based computer-aided diagnostic (AIbased CAD) systems that can provide non-invasive, early, and accurate diagnosis of a given medical condition. These AI-based CAD systems have proven themselves to be reproducible and have the generalization ability to diagnose new unseen cases with several diseases and medical conditions in different organs (e.g., kidneys, prostate, brain, liver, lung, breast, and bladder). In this dissertation, we will focus on the role of such AI-based CAD systems in early diagnosis of two kidney diseases, namely: acute rejection (AR) post kidney transplantation and renal cancer (RC). A new renal computer-assisted diagnostic (Renal-CAD) system was developed to precisely diagnose AR post kidney transplantation at an early stage. The developed Renal-CAD system perform the following main steps: (1) auto-segmentation of the renal allograft from surrounding tissues from diffusion weighted magnetic resonance imaging (DW-MRI) and blood oxygen level-dependent MRI (BOLD-MRI), (2) extraction of image markers, namely: voxel-wise apparent diffusion coefficients (ADCs) are calculated from DW-MRI scans at 11 different low and high b-values and then represented as cumulative distribution functions (CDFs) and extraction of the transverse relaxation rate (R2*) values from the segmented kidneys using BOLD-MRI scans at different echotimes, (3) integration of multimodal image markers with the associated clinical biomarkers, serum creatinine (SCr) and creatinine clearance (CrCl), and (4) diagnosing renal allograft status as nonrejection (NR) or AR by utilizing these integrated biomarkers and the developed deep learning classification model built on stacked auto-encoders (SAEs). Using a leaveone- subject-out cross-validation approach along with SAEs on a total of 30 patients with transplanted kidney (AR = 10 and NR = 20), the Renal-CAD system demonstrated 93.3% accuracy, 90.0% sensitivity, and 95.0% specificity in differentiating AR from NR. Robustness of the Renal-CAD system was also confirmed by the area under the curve value of 0.92. Using a stratified 10-fold cross-validation approach, the Renal-CAD system demonstrated its reproduciblity and robustness with a diagnostic accuracy of 86.7%, sensitivity of 80.0%, specificity of 90.0%, and AUC of 0.88. In addition, a new renal cancer CAD (RC-CAD) system for precise diagnosis of RC at an early stage was developed, which incorporates the following main steps: (1) estimating the morphological features by applying a new parametric spherical harmonic technique, (2) extracting appearance-based features, namely: first order textural features are calculated and second order textural features are extracted after constructing the graylevel co-occurrence matrix (GLCM), (3) estimating the functional features by constructing wash-in/wash-out slopes to quantify the enhancement variations across different contrast enhanced computed tomography (CE-CT) phases, (4) integrating all the aforementioned features and modeling a two-stage multilayer perceptron artificial neural network (MLPANN) classifier to classify the renal tumor as benign or malignant and identify the malignancy subtype. On a total of 140 RC patients (malignant = 70 patients (ccRCC = 40 and nccRCC = 30) and benign angiomyolipoma tumors = 70), the developed RC-CAD system was validated using a leave-one-subject-out cross-validation approach. The developed RC-CAD system achieved a sensitivity of 95.3% ± 2.0%, a specificity of 99.9% ± 0.4%, and Dice similarity coefficient of 0.98 ± 0.01 in differentiating malignant from benign renal tumors, as well as an overall accuracy of 89.6% ± 5.0% in the sub-typing of RCC. The diagnostic abilities of the developed RC-CAD system were further validated using a randomly stratified 10-fold cross-validation approach. The results obtained using the proposed MLP-ANN classification model outperformed other machine learning classifiers (e.g., support vector machine, random forests, and relational functional gradient boosting) as well as other different approaches from the literature. In summary, machine and deep learning approaches have shown potential abilities to be utilized to build AI-based CAD systems. This is evidenced by the promising diagnostic performance obtained by both Renal-CAD and RC-CAD systems. For the Renal- CAD, the integration of functional markers extracted from multimodal MRIs with clinical biomarkers using SAEs classification model, potentially improved the final diagnostic results evidenced by high accuracy, sensitivity, and specificity. The developed Renal-CAD demonstrated high feasibility and efficacy for early, accurate, and non-invasive identification of AR. For the RC-CAD, integrating morphological, textural, and functional features extracted from CE-CT images using a MLP-ANN classification model eventually enhanced the final results in terms of accuracy, sensitivity, and specificity, making the proposed RC-CAD a reliable noninvasive diagnostic tool for RC. The early and accurate diagnosis of AR or RC will help physicians to provide early intervention with the appropriate treatment plan to prolong the life span of the diseased kidney, increase the survival chance of the patient, and thus improve the healthcare outcome in the U.S. and worldwide

Contributions to the study of Austism Spectrum Brain conectivity

164 p.Autism Spectrum Disorder (ASD) is a largely prevalent neurodevelopmental condition with a big social and economical impact affecting the entire life of families. There is an intense search for biomarkers that can be assessed as early as possible in order to initiate treatment and preparation of the family to deal with the challenges imposed by the condition. Brain imaging biomarkers have special interest. Specifically, functional connectivity data extracted from resting state functional magnetic resonance imaging (rs-fMRI) should allow to detect brain connectivity alterations. Machine learning pipelines encompass the estimation of the functional connectivity matrix from brain parcellations, feature extraction and building classification models for ASD prediction. The works reported in the literature are very heterogeneous from the computational and methodological point of view. In this Thesis we carry out a comprehensive computational exploration of the impact of the choices involved while building these machine learning pipelines