A non-invasive diagnostic system for early assessment of acute renal transplant rejection.

Early diagnosis of acute renal transplant rejection (ARTR) is of immense importance for appropriate therapeutic treatment administration. Although the current diagnostic technique is based on renal biopsy, it is not preferred due to its invasiveness, recovery time (1-2 weeks), and potential for complications, e.g., bleeding and/or infection. In this thesis, a computer-aided diagnostic (CAD) system for early detection of ARTR from 4D (3D + b-value) diffusion-weighted (DW) MRI data is developed. The CAD process starts from a 3D B-spline-based data alignment (to handle local deviations due to breathing and heart beat) and kidney tissue segmentation with an evolving geometric (level-set-based) deformable model. The latter is guided by a voxel-wise stochastic speed function, which follows from a joint kidney-background Markov-Gibbs random field model accounting for an adaptive kidney shape prior and for on-going visual kidney-background appearances. A cumulative empirical distribution of apparent diffusion coefficient (ADC) at different b-values of the segmented DW-MRI is considered a discriminatory transplant status feature. Finally, a classifier based on deep learning of a non-negative constrained stacked auto-encoder is employed to distinguish between rejected and non-rejected renal transplants. In the “leave-one-subject-out” experiments on 53 subjects, 98% of the subjects were correctly classified (namely, 36 out of 37 rejected transplants and 16 out of 16 nonrejected ones). Additionally, a four-fold cross-validation experiment was performed, and an average accuracy of 96% was obtained. These experimental results hold promise of the proposed CAD system as a reliable non-invasive diagnostic tool

A novel NMF-based DWI CAD framework for prostate cancer.

In this thesis, a computer aided diagnostic (CAD) framework for detecting prostate cancer in DWI data is proposed. The proposed CAD method consists of two frameworks that use nonnegative matrix factorization (NMF) to learn meaningful features from sets of high-dimensional data. The first technique, is a three dimensional (3D) level-set DWI prostate segmentation algorithm guided by a novel probabilistic speed function. This speed function is driven by the features learned by NMF from 3D appearance, shape, and spatial data. The second technique, is a probabilistic classifier that seeks to label a prostate segmented from DWI data as either alignat, contain cancer, or benign, containing no cancer. This approach uses a NMF-based feature fusion to create a feature space where data classes are clustered. In addition, using DWI data acquired at a wide range of b-values (i.e. magnetic field strengths) is investigated. Experimental analysis indicates that for both of these frameworks, using NMF producing more accurate segmentation and classification results, respectively, and that combining the information from DWI data at several b-values can assist in detecting prostate cancer

Computational methods to predict and enhance decision-making with biomedical data.

The proposed research applies machine learning techniques to healthcare applications. The core ideas were using intelligent techniques to find automatic methods to analyze healthcare applications. Different classification and feature extraction techniques on various clinical datasets are applied. The datasets include: brain MR images, breathing curves from vessels around tumor cells during in time, breathing curves extracted from patients with successful or rejected lung transplants, and lung cancer patients diagnosed in US from in 2004-2009 extracted from SEER database. The novel idea on brain MR images segmentation is to develop a multi-scale technique to segment blood vessel tissues from similar tissues in the brain. By analyzing the vascularization of the cancer tissue during time and the behavior of vessels (arteries and veins provided in time), a new feature extraction technique developed and classification techniques was used to rank the vascularization of each tumor type. Lung transplantation is a critical surgery for which predicting the acceptance or rejection of the transplant would be very important. A review of classification techniques on the SEER database was developed to analyze the survival rates of lung cancer patients, and the best feature vector that can be used to predict the most similar patients are analyzed

A novel MRA-based framework for the detection of changes in cerebrovascular blood pressure.

Background: High blood pressure (HBP) affects 75 million adults and is the primary or contributing cause of mortality in 410,000 adults each year in the United States. Chronic HBP leads to cerebrovascular changes and is a significant contributor for strokes, dementia, and cognitive impairment. Non-invasive measurement of changes in cerebral vasculature and blood pressure (BP) may enable physicians to optimally treat HBP patients. This manuscript describes a method to non-invasively quantify changes in cerebral vasculature and BP using Magnetic Resonance Angiography (MRA) imaging. Methods: MRA images and BP measurements were obtained from patients (n=15, M=8, F=7, Age= 49.2 ± 7.3 years) over a span of 700 days. A novel segmentation algorithm was developed to identify brain vasculature from surrounding tissue. The data was processed to calculate the vascular probability distribution function (PDF); a measure of the vascular diameters in the brain. The initial (day 0) PDF and final (day 700) PDF were used to correlate the changes in cerebral vasculature and BP. Correlation was determined by a mixed effects linear model analysis. Results: The segmentation algorithm had a 99.9% specificity and 99.7% sensitivity in identifying and delineating cerebral vasculature. The PDFs had a statistically significant correlation to BP changes below the circle of Willis (p-value = 0.0007), but not significant (p-value = 0.53) above the circle of Willis, due to smaller blood vessels. Conclusion: Changes in cerebral vasculature and pressure can be non-invasively obtained through MRA image analysis, which may be a useful tool for clinicians to optimize medical management of HBP

Sparse feature learning for image analysis in segmentation, classification, and disease diagnosis.

The success of machine learning algorithms generally depends on intermediate data representation, called features that disentangle the hidden factors of variation in data. Moreover, machine learning models are required to be generalized, in order to reduce the specificity or bias toward the training dataset. Unsupervised feature learning is useful in taking advantage of large amount of unlabeled data, which is available to capture these variations. However, learned features are required to capture variational patterns in data space. In this dissertation, unsupervised feature learning with sparsity is investigated for sparse and local feature extraction with application to lung segmentation, interpretable deep models, and Alzheimer\u27s disease classification. Nonnegative Matrix Factorization, Autoencoder and 3D Convolutional Autoencoder are used as architectures or models for unsupervised feature learning. They are investigated along with nonnegativity, sparsity and part-based representation constraints for generalized and transferable feature extraction

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

3D Kidney Segmentation from Abdominal Images Using Spatial-Appearance Models

Kidney segmentation is an essential step in developing any noninvasive computer-assisted diagnostic system for renal function assessment. This paper introduces an automated framework for 3D kidney segmentation from dynamic computed tomography (CT) images that integrates discriminative features from the current and prior CT appearances into a random forest classification approach. To account for CT images’ inhomogeneities, we employ discriminate features that are extracted from a higher-order spatial model and an adaptive shape model in addition to the first-order CT appearance. To model the interactions between CT data voxels, we employed a higher-order spatial model, which adds the triple and quad clique families to the traditional pairwise clique family. The kidney shape prior model is built using a set of training CT data and is updated during segmentation using not only region labels but also voxels’ appearances in neighboring spatial voxel locations. Our framework performance has been evaluated on in vivo dynamic CT data collected from 20 subjects and comprises multiple 3D scans acquired before and after contrast medium administration. Quantitative evaluation between manually and automatically segmented kidney contours using Dice similarity, percentage volume differences, and 95th-percentile bidirectional Hausdorff distances confirms the high accuracy of our approach

Machine learning approaches for lung cancer diagnosis.

The enormity of changes and development in the field of medical imaging technology is hard to fathom, as it does not just represent the technique and process of constructing visual representations of the body from inside for medical analysis and to reveal the internal structure of different organs under the skin, but also it provides a noninvasive way for diagnosis of various disease and suggest an efficient ways to treat them. While data surrounding all of our lives are stored and collected to be ready for analysis by data scientists, medical images are considered a rich source that could provide us with a huge amount of data, that could not be read easily by physicians and radiologists, with valuable information that could be used in smart ways to discover new knowledge from these vast quantities of data. Therefore, the design of computer-aided diagnostic (CAD) system, that can be approved for use in clinical practice that aid radiologists in diagnosis and detecting potential abnormalities, is of a great importance. This dissertation deals with the development of a CAD system for lung cancer diagnosis, which is the second most common cancer in men after prostate cancer and in women after breast cancer. Moreover, lung cancer is considered the leading cause of cancer death among both genders in USA. Recently, the number of lung cancer patients has increased dramatically worldwide and its early detection doubles a patient’s chance of survival. Histological examination through biopsies is considered the gold standard for final diagnosis of pulmonary nodules. Even though resection of pulmonary nodules is the ideal and most reliable way for diagnosis, there is still a lot of different methods often used just to eliminate the risks associated with the surgical procedure. Lung nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. A pulmonary nodule is the first indication to start diagnosing lung cancer. Lung nodules can be benign (normal subjects) or malignant (cancerous subjects). Large (generally defined as greater than 2 cm in diameter) malignant nodules can be easily detected with traditional CT scanning techniques. However, the diagnostic options for small indeterminate nodules are limited due to problems associated with accessing small tumors. Therefore, additional diagnostic and imaging techniques which depends on the nodules’ shape and appearance are needed. The ultimate goal of this dissertation is to develop a fast noninvasive diagnostic system that can enhance the accuracy measures of early lung cancer diagnosis based on the well-known hypotheses that malignant nodules have different shape and appearance than benign nodules, because of the high growth rate of the malignant nodules. The proposed methodologies introduces new shape and appearance features which can distinguish between benign and malignant nodules. To achieve this goal a CAD system is implemented and validated using different datasets. This CAD system uses two different types of features integrated together to be able to give a full description to the pulmonary nodule. These two types are appearance features and shape features. For the appearance features different texture appearance descriptors are developed, namely the 3D histogram of oriented gradient, 3D spherical sector isosurface histogram of oriented gradient, 3D adjusted local binary pattern, 3D resolved ambiguity local binary pattern, multi-view analytical local binary pattern, and Markov Gibbs random field. Each one of these descriptors gives a good description for the nodule texture and the level of its signal homogeneity which is a distinguishable feature between benign and malignant nodules. For the shape features multi-view peripheral sum curvature scale space, spherical harmonics expansions, and different group of fundamental geometric features are utilized to describe the nodule shape complexity. Finally, the fusion of different combinations of these features, which is based on two stages is introduced. The first stage generates a primary estimation for every descriptor. Followed by the second stage that consists of an autoencoder with a single layer augmented with a softmax classifier to provide us with the ultimate classification of the nodule. These different combinations of descriptors are combined into different frameworks that are evaluated using different datasets. The first dataset is the Lung Image Database Consortium which is a benchmark publicly available dataset for lung nodule detection and diagnosis. The second dataset is our local acquired computed tomography imaging data that has been collected from the University of Louisville hospital and the research protocol was approved by the Institutional Review Board at the University of Louisville (IRB number 10.0642). These frameworks accuracy was about 94%, which make the proposed frameworks demonstrate promise to be valuable tool for the detection of lung cancer

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

Diffusion-weighted magnetic resonance imaging in diagnosing graft dysfunction : a non-invasive alternative to renal biopsy.

The thesis is divided into three parts. The first part focuses on background information including how the kidney functions, diseases, and available kidney disease treatment strategies. In addition, the thesis provides information on imaging instruments and how they can be used to diagnose renal graft dysfunction. The second part focuses on elucidating the parameters linked with highly accurate diagnosis of rejection. Four parameters categories were tested: clinical biomarkers alone, individual mean apparent diffusion coefficient (ADC) at 11-different b- values, mean ADCs of certain groups of b-value, and fusion of clinical biomarkers and all b-values. The most accurate model was found to be when the b-value of b=100 s/mm2 and b=700 s/mm2 were fused. The third part of this thesis focuses on a study that uses Diffusion-Weighted MRI to diagnose and differentiate two types of renal rejection. The system was found to correctly differentiate the two types of rejection with a 98% accuracy. The last part of this thesis concludes the work that has been done and states the possible trends and future avenues