Automated Decision Support System for Traumatic Injuries

With trauma being one of the leading causes of death in the U.S., automated decision support systems that can accurately detect traumatic injuries and predict their outcomes are crucial for preventing secondary injuries and guiding care management. My dissertation research incorporates machine learning and image processing techniques to extract knowledge from structured (e.g., electronic health records) and unstructured (e.g., computed tomography images) data to generate real-time, robust, quantitative trauma diagnosis and prognosis. This work addresses two challenges: 1) incorporating clinical domain knowledge into deep convolutional neural networks using classical image processing techniques and 2) using post-hoc explainers to align black box predictive machine learning models with clinical domain knowledge. Addressing these challenges is necessary for developing trustworthy clinical decision-support systems that can be generalized across the healthcare system. Motivated by this goal, we introduce an explainable and expert-guided machine learning framework to predict the outcome of traumatic brain injury. We also propose image processing approaches to automatically assess trauma from computed tomography scans. This research comprises four projects. In the first project, we propose an explainable hierarchical machine learning framework to predict the long-term functional outcome of traumatic brain injury using information available in electronic health records. This information includes demographic data, baseline features, radiology reports, laboratory values, injury severity scores, and medical history. To build such a framework, we peer inside the black-box machine learning models to explain their rationale for each predicted risk score. Accordingly, additional layers of statistical inference and human expert validation are added to the model, which ensures the predicted risk score’s trustworthiness. We demonstrate that imposing statistical and domain knowledge “checks and balances” not only does not adversely affect the performance of the machine learning classifier but also makes it more reliable. In the second project, we introduce a framework for detecting and assessing the severity of brain subdural hematomas. First, the hematoma is segmented using a combination of hand-crafted and deep learning features. Next, we calculate the volume of the injured region to quantitatively assess its severity. We show that the combination of classical image processing and deep learning can outperform deep-learning-only methods to achieve improved average performance and robustness. In the third project, we develop a framework to identify and assess liver trauma by calculating the percentage of the liver parenchyma disrupted by trauma. First, liver parenchyma and trauma masks are segmented by employing a deep learning backbone. Next, these segmented regions are refined with respect to the domain knowledge about the location and intensity distribution of liver trauma. This framework accurately estimated the severity of liver parenchyma trauma. In the final project, we propose a kidney segmentation method for patients with blunt abdominal trauma. This model incorporates machine learning and active contour modeling to generate kidney masks on abdominal CT images. The resultant of this component can provide a region of interest for screening kidney traumas in future studies. Together, the four projects discussed in this thesis contribute to diagnosis and prognosis of trauma across multiple body regions. They provide a quantitative assessment of traumas that is a more accurate measurement of the risk for adverse health outcomes as an alternative to current qualitative and sometimes subjective current clinical practice.PHDBioinformaticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/168065/1/negarf_1.pd

Cluster analysis of the signal curves in perfusion DCE-MRI datasets

Pathological studies show that tumors consist of different sub-regions with more homogeneous vascular properties during their growth. In addition, destroying tumor's blood supply is the target of most cancer therapies. Finding the sub-regions in the tissue of interest with similar perfusion patterns provides us with valuable information about tissue structure and angiogenesis. This information on cancer therapy, for example, can be used in monitoring the response of the cancer treatment to the drug. Cluster analysis of perfusion curves assays to find sub-regions with a similar perfusion pattern. The present work focuses on the cluster analysis of perfusion curves, measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The study, besides searching for the proper clustering method, follows two other major topics, the choice of an appropriate similarity measure, and determining the number of clusters. These three subjects are connected to each other in such a way that success in one direction will help solving the other problems. This work introduces a new similarity measure, parallelism measure (PM), for comparing the parallelism in the washout phase of the signal curves. Most of the previous works used the Euclidean distance as the measure of dissimilarity. However, the Euclidean distance does not take the patterns of the signal curves into account and therefore for comparing the signal curves is not sufficient. To combine the advantages of both measures a two-steps clustering is developed. The two-steps clustering uses two different similarity measures, the introduced PM measure and Euclidean distance in two consecutive steps. The results of two-steps clustering are compared with the results of other clustering methods. The two-steps clustering besides good performance has some other advantages. The granularity and the number of clusters are controlled by thresholds defined by considering the noise in signal curves. The method is easy to implement and is robust against noise. The focus of the work is mainly the cluster analysis of breast tumors in DCE-MRI datasets. The possibility to adopt the method for liver datasets is studied as well

Multidimensional image analysis of cardiac function in MRI

Cardiac morphology is a key indicator of cardiac health. Important metrics that are currently in clinical use are left-ventricle cardiac ejection fraction, cardiac muscle (myocardium) mass, myocardium thickness and myocardium thickening over the cardiac cycle. Advances in imaging technologies have led to an increase in temporal and spatial resolution. Such an increase in data presents a laborious task for medical practitioners to analyse. In this thesis, measurement of the cardiac left-ventricle function is achieved by developing novel methods for the automatic segmentation of the left-ventricle blood-pool and the left ventricle myocardium boundaries. A preliminary challenge faced in this task is the removal of noise from Magnetic Resonance Imaging (MRI) data, which is addressed by using advanced data filtering procedures. Two mechanisms for left-ventricle segmentation are employed. Firstly segmentation of the left ventricle blood-pool for the measurement of ejection fraction is undertaken in the signal intensity domain. Utilising the high discrimination between blood and tissue, a novel methodology based on a statistical partitioning method offers success in localising and segmenting the blood pool of the left ventricle. From this initialisation, the estimation of the outer wall (epi-cardium) of the left ventricle can be achieved using gradient information and prior knowledge. Secondly, a more involved method for extracting the myocardium of the leftventricle is developed, that can better perform segmentation in higher dimensions. Spatial information is incorporated in the segmentation by employing a gradient-based boundary evolution. A level-set scheme is implemented and a novel formulation for the extraction of the cardiac muscle is introduced. Two surfaces, representing the inner and the outer boundaries of the left-ventricle, are simultaneously evolved using a coupling function and supervised with a probabilistic model of expertly assisted manual segmentations

Analysis of contrast-enhanced medical images.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection–the immunological response of the human immune system to a foreign kidney–is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient’s chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today’s CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images

The Probabilistic Active Shape Model: From Model Construction to Flexible Medical Image Segmentation

Automatic processing of three-dimensional image data acquired with computed tomography or magnetic resonance imaging plays an increasingly important role in medicine. For example, the automatic segmentation of anatomical structures in tomographic images allows to generate three-dimensional visualizations of a patient’s anatomy and thereby supports surgeons during planning of various kinds of surgeries. Because organs in medical images often exhibit a low contrast to adjacent structures, and because the image quality may be hampered by noise or other image acquisition artifacts, the development of segmentation algorithms that are both robust and accurate is very challenging. In order to increase the robustness, the use of model-based algorithms is mandatory, as for example algorithms that incorporate prior knowledge about an organ’s shape into the segmentation process. Recent research has proven that Statistical Shape Models are especially appropriate for robust medical image segmentation. In these models, the typical shape of an organ is learned from a set of training examples. However, Statistical Shape Models have two major disadvantages: The construction of the models is relatively difficult, and the models are often used too restrictively, such that the resulting segmentation does not delineate the organ exactly. This thesis addresses both problems: The first part of the thesis introduces new methods for establishing correspondence between training shapes, which is a necessary prerequisite for shape model learning. The developed methods include consistent parameterization algorithms for organs with spherical and genus 1 topology, as well as a nonrigid mesh registration algorithm for shapes with arbitrary topology. The second part of the thesis presents a new shape model-based segmentation algorithm that allows for an accurate delineation of organs. In contrast to existing approaches, it is possible to integrate not only linear shape models into the algorithm, but also nonlinear shape models, which allow for a more specific description of an organ’s shape variation. The proposed segmentation algorithm is evaluated in three applications to medical image data: Liver and vertebra segmentation in contrast-enhanced computed tomography scans, and prostate segmentation in magnetic resonance images