Developing advanced mathematical models for detecting abnormalities in 2D/3D medical structures.

Detecting abnormalities in two-dimensional (2D) and three-dimensional (3D) medical structures is among the most interesting and challenging research areas in the medical imaging field. Obtaining the desired accurate automated quantification of abnormalities in medical structures is still very challenging. This is due to a large and constantly growing number of different objects of interest and associated abnormalities, large variations of their appearances and shapes in images, different medical imaging modalities, and associated changes of signal homogeneity and noise for each object. The main objective of this dissertation is to address these problems and to provide proper mathematical models and techniques that are capable of analyzing low and high resolution medical data and providing an accurate, automated analysis of the abnormalities in medical structures in terms of their area/volume, shape, and associated abnormal functionality. This dissertation presents different preliminary mathematical models and techniques that are applied in three case studies: (i) detecting abnormal tissue in the left ventricle (LV) wall of the heart from delayed contrast-enhanced cardiac magnetic resonance images (MRI), (ii) detecting local cardiac diseases based on estimating the functional strain metric from cardiac cine MRI, and (iii) identifying the abnormalities in the corpus callosum (CC) brain structure—the largest fiber bundle that connects the two hemispheres in the brain—for subjects that suffer from developmental brain disorders. For detecting the abnormal tissue in the heart, a graph-cut mathematical optimization model with a cost function that accounts for the object’s visual appearance and shape is used to segment the the inner cavity. The model is further integrated with a geometric model (i.e., a fast marching level set model) to segment the outer border of the myocardial wall (the LV). Then the abnormal tissue in the myocardium wall (also called dead tissue, pathological tissue, or infarct area) is identified based on a joint Markov-Gibbs random field (MGRF) model of the image and its region (segmentation) map that accounts for the pixel intensities and the spatial interactions between the pixels. Experiments with real in-vivo data and comparative results with ground truth (identified by a radiologist) and other approaches showed that the proposed framework can accurately detect the pathological tissue and can provide useful metrics for radiologists and clinicians. To estimate the strain from cardiac cine MRI, a novel method based on tracking the LV wall geometry is proposed. To achieve this goal, a partial differential equation (PDE) method is applied to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. The main advantage of the proposed tracking method over traditional texture-based methods is its ability to track the movement and rotation of the LV wall based on tracking the geometric features of the inner, mid-, and outer walls of the LV. This overcomes noise sources that come from scanner and heart motion. To identify the abnormalities in the CC from brain MRI, the CCs are aligned using a rigid registration model and are segmented using a shape-appearance model. Then, they are mapped to a simple unified space for analysis. This work introduces a novel cylindrical mapping model, which is conformal (i.e., one to one transformation and bijective), that enables accurate 3D shape analysis of the CC in the cylindrical domain. The framework can detect abnormalities in all divisions of the CC (i.e., splenium, rostrum, genu and body). In addition, it offers a whole 3D analysis of the CC abnormalities instead of only area-based analysis as done by previous groups. The initial classification results based on the centerline length and CC thickness suggest that the proposed CC shape analysis is a promising supplement to the current techniques for diagnosing dyslexia. The proposed techniques in this dissertation have been successfully tested on complex synthetic and MR images and can be used to advantage in many of today’s clinical applications of computer-assisted medical diagnostics and intervention

Shape analysis of the human brain.

Autism is a complex developmental disability that has dramatically increased in prevalence, having a decisive impact on the health and behavior of children. Methods used to detect and recommend therapies have been much debated in the medical community because of the subjective nature of diagnosing autism. In order to provide an alternative method for understanding autism, the current work has developed a 3-dimensional state-of-the-art shape based analysis of the human brain to aid in creating more accurate diagnostic assessments and guided risk analyses for individuals with neurological conditions, such as autism. Methods: The aim of this work was to assess whether the shape of the human brain can be used as a reliable source of information for determining whether an individual will be diagnosed with autism. The study was conducted using multi-center databases of magnetic resonance images of the human brain. The subjects in the databases were analyzed using a series of algorithms consisting of bias correction, skull stripping, multi-label brain segmentation, 3-dimensional mesh construction, spherical harmonic decomposition, registration, and classification. The software algorithms were developed as an original contribution of this dissertation in collaboration with the BioImaging Laboratory at the University of Louisville Speed School of Engineering. The classification of each subject was used to construct diagnoses and therapeutic risk assessments for each patient. Results: A reliable metric for making neurological diagnoses and constructing therapeutic risk assessment for individuals has been identified. The metric was explored in populations of individuals having autism spectrum disorders, dyslexia, Alzheimers disease, and lung cancer. Conclusion: Currently, the clinical applicability and benefits of the proposed software approach are being discussed by the broader community of doctors, therapists, and parents for use in improving current methods by which autism spectrum disorders are diagnosed and understood

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

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 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

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

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

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

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

A non-invasive image based system for early diagnosis of prostate cancer.

Prostate cancer is the second most fatal cancer experienced by American males. The average American male has a 16.15% chance of developing prostate cancer, which is 8.38% higher than lung cancer, the second most likely cancer. The current in-vitro techniques that are based on analyzing a patients blood and urine have several limitations concerning their accuracy. In addition, the prostate Specific Antigen (PSA) blood-based test, has a high chance of false positive diagnosis, ranging from 28%-58%. Yet, biopsy remains the gold standard for the assessment of prostate cancer, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The major limitation of the relatively small needle biopsy samples is the higher possibility of producing false positive diagnosis. Moreover, the visual inspection system (e.g., Gleason grading system) is not quantitative technique and different observers may classify a sample differently, leading to discrepancies in the diagnosis. As reported in the literature that the early detection of prostate cancer is a crucial step for decreasing prostate cancer related deaths. Thus, there is an urgent need for developing objective, non-invasive image based technology for early detection of prostate cancer. The objective of this dissertation is to develop a computer vision methodology, later translated into a clinically usable software tool, which can improve sensitivity and specificity of early prostate cancer diagnosis based on the well-known hypothesis that malignant tumors are will connected with the blood vessels than the benign tumors. Therefore, using either Diffusion Weighted Magnetic Resonance imaging (DW-MRI) or Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), we will be able to interrelate the amount of blood in the detected prostate tumors by estimating either the Apparent Diffusion Coefficient (ADC) in the prostate with the malignancy of the prostate tumor or perfusion parameters. We intend to validate this hypothesis by demonstrating that automatic segmentation of the prostate from either DW-MRI or DCE-MRI after handling its local motion, provides discriminatory features for early prostate cancer diagnosis. The proposed CAD system consists of three majors components, the first two of which constitute new research contributions to a challenging computer vision problem. The three main components are: (1) A novel Shape-based segmentation approach to segment the prostate from either low contrast DW-MRI or DCE-MRI data; (2) A novel iso-contours-based non-rigid registration approach to ensure that we have voxel-on-voxel matches of all data which may be more difficult due to gross patient motion, transmitted respiratory effects, and intrinsic and transmitted pulsatile effects; and (3) Probabilistic models for the estimated diffusion and perfusion features for both malignant and benign tumors. Our results showed a 98% classification accuracy using Leave-One-Subject-Out (LOSO) approach based on the estimated ADC for 30 patients (12 patients diagnosed as malignant; 18 diagnosed as benign). These results show the promise of the proposed image-based diagnostic technique as a supplement to current technologies for diagnosing prostate cancer