Synergistic Visualization And Quantitative Analysis Of Volumetric Medical Images

The medical diagnosis process starts with an interview with the patient, and continues with the physical exam. In practice, the medical professional may require additional screenings to precisely diagnose. Medical imaging is one of the most frequently used non-invasive screening methods to acquire insight of human body. Medical imaging is not only essential for accurate diagnosis, but also it can enable early prevention. Medical data visualization refers to projecting the medical data into a human understandable format at mediums such as 2D or head-mounted displays without causing any interpretation which may lead to clinical intervention. In contrast to the medical visualization, quantification refers to extracting the information in the medical scan to enable the clinicians to make fast and accurate decisions. Despite the extraordinary process both in medical visualization and quantitative radiology, efforts to improve these two complementary fields are often performed independently and synergistic combination is under-studied. Existing image-based software platforms mostly fail to be used in routine clinics due to lack of a unified strategy that guides clinicians both visually and quan- titatively. Hence, there is an urgent need for a bridge connecting the medical visualization and automatic quantification algorithms in the same software platform. In this thesis, we aim to fill this research gap by visualizing medical images interactively from anywhere, and performing a fast, accurate and fully-automatic quantification of the medical imaging data. To end this, we propose several innovative and novel methods. Specifically, we solve the following sub-problems of the ul- timate goal: (1) direct web-based out-of-core volume rendering, (2) robust, accurate, and efficient learning based algorithms to segment highly pathological medical data, (3) automatic landmark- ing for aiding diagnosis and surgical planning and (4) novel artificial intelligence algorithms to determine the sufficient and necessary data to derive large-scale problems

Towards AI-Assisted Disease Diagnosis: Learning Deep Feature Representations for Medical Image Analysis

Artificial Intelligence (AI) has impacted our lives in many meaningful ways. For our research, we focus on improving disease diagnosis systems by analyzing medical images using AI, specifically deep learning technologies. The recent advances in deep learning technologies are leading to enhanced performance for medical image analysis and computer-aided disease diagnosis. In this dissertation, we explore a major research area in medical image analysis - Image classification. Image classification is the process to assign an image a label from a fixed set of categories. For our research, we focus on the problem of Alzheimer\u27s Disease (AD) diagnosis from 3D structural Magnetic Resonance Imaging (sMRI) and Positron Emission Tomography (PET) brain scans. Alzheimer\u27s Disease is a severe neurological disorder. In this dissertation, we address challenges related to Alzheimer\u27s Disease diagnosis and propose several models for improved diagnosis. We focus on analyzing the 3D Structural MRI (sMRI) and Positron Emission Tomography (PET) brain scans to identify the current stage of Alzheimer\u27s Disease: Normal Controls (CN), Mild Cognitive Impairment (MCI), and Alzheimer\u27s Disease (AD). This dissertation demonstrates ways to improve the performance of a Convolutional Neural Network (CNN) for Alzheimer\u27s Disease diagnosis. Besides, we present approaches to solve the class-imbalance problem and improving classification performance with limited training data for medical image analysis. To understand the decision of the CNN, we present methods to visualize the behavior of a CNN model for disease diagnosis. As a case study, we analyzed brain PET scans of AD and CN patients to see how CNN discriminates among data samples of different classes. Additionally, this dissertation proposes a novel approach to generate synthetic medical images using Generative Adversarial Networks (GANs). Working with the limited dataset and small amount of annotated samples makes it difficult to develop a robust automated disease diagnosis model. Our proposed model can solve such issue and generate brain MRI and PET images for three different stages of Alzheimer\u27s Disease - Normal Control (CN), Mild Cognitive Impairment (MCI), and Alzheimer\u27s Disease (AD). Our proposed approach can be generalized to create synthetic data for other medical image analysis problems and help to develop better disease diagnosis model

Intensity Based Non-rigid Registration of 3D Whole Mouse Optical and MR Image Volumes

Novel magnetic resonance (MR) imaging techniques can be validated using accurate co-registration with histology. Whole-animal histological sections allow for simultaneous analysis of multiple tissues, and may also aid in registration by providing contextual information and structural support to tissues which if isolated from the body would be difficult to register. This thesis explores the feasibility of co-registration between whole mouse histology with 3D MR images using an intermediate optical image volume acquired during tissue sectioning. Of the two transformations required for this approach, 3D co-registration of MR and optical images is more challenging to perform due to changes in contrast, slice orientation, and resolution between these modalities. Here, an automated non-rigid registration technique utilizing mutual information is proposed to accurately register 3D whole mouse optical and MR images as a first step towards automated registration of histology. Validation of this technique was accomplished through calculation of post-registration target registration error

Quantitative MRI correlates of hippocampal and neocortical pathology in intractable temporal lobe epilepsy

Intractable or drug-resistant epilepsy occurs in over 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to investigate histopathological correlates of quantitative relaxometry and DTI from hippocampal and neocortical specimens of intractable TLE patients. To achieve this goal I developed and evaluated a pipeline for histology to in-vivo MRI image registration, which finds dense spatial correspondence between both modalities. This protocol was divided in two steps whereby sparsely sectioned histology from temporal lobe specimens was first registered to the intermediate ex-vivo MRI which is then registered to the in-vivo MRI, completing a pipeline for histology to in-vivo MRI registration. When correlating relaxometry and DTI with neuronal density and morphology in the temporal lobe neocortex, I found T1 to be a predictor of neuronal density in the neocortical GM and demonstrated that employing multi-parametric MRI (combining T1 and FA together) provided a significantly better fit than each parameter alone in predicting density of neurons. This work was the first to relate in-vivo T1 and FA values to the proportion of neurons in GM. When investigating these quantitative multimodal parameters with histological features within the hippocampal subfields, I demonstrated that MD correlates with neuronal density and size, and can act as a marker for neuron integrity within the hippocampus. More importantly, this work was the first to highlight the potential of subfield relaxometry and diffusion parameters (mainly T2 and MD) as well as volumetry in predicting the extent of cell loss per subfield pre-operatively, with a precision so far unachievable. These results suggest that high-resolution quantitative MRI sequences could impact clinical practice for pre-operative evaluation and prediction of surgical outcomes of intractable epilepsy

Landmark Localization, Feature Matching and Biomarker Discovery from Magnetic Resonance Images

The work presented in this thesis proposes several methods that can be roughly divided into three different categories: I) landmark localization in medical images, II) feature matching for image registration, and III) biomarker discovery in neuroimaging. The first part deals with the identification of anatomical landmarks. The motivation stems from the fact that the manual identification and labeling of these landmarks is very time consuming and prone to observer errors, especially when large datasets must be analyzed. In this thesis we present three methods to tackle this challenge: A landmark descriptor based on local self-similarities (SS), a subspace building framework based on manifold learning and a sparse coding landmark descriptor based on data-specific learned dictionary basis. The second part of this thesis deals with finding matching features between a pair of images. These matches can be used to perform a registration between them. Registration is a powerful tool that allows mapping images in a common space in order to aid in their analysis. Accurate registration can be challenging to achieve using intensity based registration algorithms. Here, a framework is proposed for learning correspondences in pairs of images by matching SS features and random sample and consensus (RANSAC) is employed as a robust model estimator to learn a deformation model based on feature matches. Finally, the third part of the thesis deals with biomarker discovery using machine learning. In this section a framework for feature extraction from learned low-dimensional subspaces that represent inter-subject variability is proposed. The manifold subspace is built using data-driven regions of interest (ROI). These regions are learned via sparse regression, with stability selection. Also, probabilistic distribution models for different stages in the disease trajectory are estimated for different class populations in the low-dimensional manifold and used to construct a probabilistic scoring function.Open Acces

Volumetric MRI Reconstruction from 2D Slices in the Presence of Motion

Despite recent advances in acquisition techniques and reconstruction algorithms, magnetic resonance imaging (MRI) remains challenging in the presence of motion. To mitigate this, ultra-fast two-dimensional (2D) MRI sequences are often used in clinical practice to acquire thick, low-resolution (LR) 2D slices to reduce in-plane motion. The resulting stacks of thick 2D slices typically provide high-quality visualizations when viewed in the in-plane direction. However, the low spatial resolution in the through-plane direction in combination with motion commonly occurring between individual slice acquisitions gives rise to stacks with overall limited geometric integrity. In further consequence, an accurate and reliable diagnosis may be compromised when using such motion-corrupted, thick-slice MRI data. This thesis presents methods to volumetrically reconstruct geometrically consistent, high-resolution (HR) three-dimensional (3D) images from motion-corrupted, possibly sparse, low-resolution 2D MR slices. It focuses on volumetric reconstructions techniques using inverse problem formulations applicable to a broad field of clinical applications in which associated motion patterns are inherently different, but the use of thick-slice MR data is current clinical practice. In particular, volumetric reconstruction frameworks are developed based on slice-to-volume registration with inter-slice transformation regularization and robust, complete-outlier rejection for the reconstruction step that can either avoid or efficiently deal with potential slice-misregistrations. Additionally, this thesis describes efficient Forward-Backward Splitting schemes for image registration for any combination of differentiable (not necessarily convex) similarity measure and convex (not necessarily smooth) regularization with a tractable proximal operator. Experiments are performed on fetal and upper abdominal MRI, and on historical, printed brain MR films associated with a uniquely long-term study dating back to the 1980s. The results demonstrate the broad applicability of the presented frameworks to achieve robust reconstructions with the potential to improve disease diagnosis and patient management in clinical practice