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

Hemorrhage Detection and Analysis in Traumatic Pelvic Injuries

Traumatic pelvic injuries associated with high-energy pelvic fractures are life-threatening injuries. Extensive bleeding is relatively common with pelvic fractures. However, bleeding is especially prevalent with high-energy fractures. Hemorrhage remains the major cause of death that occur within the first 24 hours after a traumatic pelvic injury. Emergent-life saving treatment is required for high-energy pelvic fractures associated with hemorrhage. A thorough understanding of potential sources of bleeding within a short period is essential for diagnosis and treatment planning. Computed Tomography (CT) images have been widely in use in identifying the potential sources of bleeding. A pelvic CT scan contains a large number of images. Analyzing each slice in a scan via simple visual inspection is very time consuming. Time is a crucial factor in emergency medicine. Therefore, a computer-assisted pelvic trauma decision-making system is advantageous for assisting physicians in fast and accurate decision making and treatment planning. The proposed project presents an automated system to detect and segment hemorrhage and combines it with the other extracted features from pelvic images and demographic data to provide recommendations to trauma caregivers for diagnosis and treatment. The first part of the project is to develop automated methods to detect arteries by incorporating bone information. This part of the project merges bone edges and segments bone using a seed growing technique. Later the segmented bone information is utilized along with the best template matching to locate arteries and extract gray level information of the located arteries in the pelvic region. The second part of the project focuses on locating the source of hemorrhage and its segmentation. The hemorrhage is segmented using a novel rule based hemorrhage segmentation approach. This approach segments hemorrhage through hemorrhage matching, rule optimization, and region growing. Later the position of hemorrhage in the image and the volume of the hemorrhage are determined to analyze hemorrhage severity. The third part of the project is to automatically classify the outcome using features extracted from the medical images and patient medical records and demographics. A multi-stage feature selection algorithm is used to select the predominant features among all the features. Finally, boosted logistic model tree is used to classify the outcome. The methods are tested on CT images of traumatic pelvic injury patients. The hemorrhage segmentation and classification results seem promising and demonstrate that the proposed method is not only capable of automatically segmenting hemorrhage and classifying outcome, but also has the potential to be used for clinical applications. Finally, the project is extended to abdominal trauma and a novel knowledge based heuristic technique is used to detect and segment spleen from the abdominal CT images. This technique is tested on a limited number of subjects and the results are promising

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 mu m. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney

Image Processing and Analysis for Preclinical and Clinical Applications

Radiomics is one of the most successful branches of research in the field of image processing and analysis, as it provides valuable quantitative information for the personalized medicine. It has the potential to discover features of the disease that cannot be appreciated with the naked eye in both preclinical and clinical studies. In general, all quantitative approaches based on biomedical images, such as positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI), have a positive clinical impact in the detection of biological processes and diseases as well as in predicting response to treatment. This Special Issue, “Image Processing and Analysis for Preclinical and Clinical Applications”, addresses some gaps in this field to improve the quality of research in the clinical and preclinical environment. It consists of fourteen peer-reviewed papers covering a range of topics and applications related to biomedical image processing and analysis

The leucocytosis of trauma

The studies in this thesis have attempted to establish the existence of the leucocytosis of trauma, to clarify its features, and to examine its possible implications for the immune response. 110 patients were studied within three hours of moderate or major injury, and a significant difference (p < 0 .0001) established between their leucocyte counts and those of 110 normal controls. Differential leucocyte counts of 42 patients gave evidence of a very early neutrophilia and lymphocytosis. The neutrophilia was maximal at 3-4 hours post-injury and resolved slowly. The lymphocytosis resolved rapidly and was commonly replaced by lymphopenia. Serial phenotype studies of lymphocytes in 28 patients showed significant reductions (p<0.01) in total lymphocytes, CD4 and CD8 lymphocytes between blood samples taken less than 4 hours and 12-24 hours after injury. CD4 lymphocyte counts were low in 24 patients (85%), of which 6 (20%) were critically low (<0.25x10⁹/L). 22 patients (78%) also had low CD8 counts. Neutrophils of trauma patients exhibited reduced adhesion to nylon fibre when suspended in their own plasma, but not in tissue culture medium. Trauma plasma induced a reduction in adhesion of normal donor neutrophils, which was reversed by pre-incubation of the neutrophils with propranolol. The leucocytosis of trauma may therefore be due in part to reduced neutrophil adhesion induced by raised adrenaline levels. Studies of neutrophil microbicidal pathways within 6 hours of injury in 23 patients showed normal responses in 21 (91%). In 8 patients studied 8 hours or more after injury, only one (12.5%) had normal responses. Electron microscopic studies of neutrophils in 17 trauma patients showed no evidence of systemic degranulation within the first four hours after injury. Taken together, these results indicate the existence of a leucocytosis of trauma, which is composed of normal cell lines. Derangements of cell function appear after 4-8 hours, and the early post-trauma phase may offer the opportunity for development of therapies to avoid later sepsis and multiple organ failure

On uncertainty propagation in image-guided renal navigation: Exploring uncertainty reduction techniques through simulation and in vitro phantom evaluation

Image-guided interventions (IGIs) entail the use of imaging to augment or replace direct vision during therapeutic interventions, with the overall goal is to provide effective treatment in a less invasive manner, as an alternative to traditional open surgery, while reducing patient trauma and shortening the recovery time post-procedure. IGIs rely on pre-operative images, surgical tracking and localization systems, and intra-operative images to provide correct views of the surgical scene. Pre-operative images are used to generate patient-specific anatomical models that are then registered to the patient using the surgical tracking system, and often complemented with real-time, intra-operative images. IGI systems are subject to uncertainty from several sources, including surgical instrument tracking / localization uncertainty, model-to-patient registration uncertainty, user-induced navigation uncertainty, as well as the uncertainty associated with the calibration of various surgical instruments and intra-operative imaging devices (i.e., laparoscopic camera) instrumented with surgical tracking sensors. All these uncertainties impact the overall targeting accuracy, which represents the error associated with the navigation of a surgical instrument to a specific target to be treated under image guidance provided by the IGI system. Therefore, understanding the overall uncertainty of an IGI system is paramount to the overall outcome of the intervention, as procedure success entails achieving certain accuracy tolerances specific to individual procedures. This work has focused on studying the navigation uncertainty, along with techniques to reduce uncertainty, for an IGI platform dedicated to image-guided renal interventions. We constructed life-size replica patient-specific kidney models from pre-operative images using 3D printing and tissue emulating materials and conducted experiments to characterize the uncertainty of both optical and electromagnetic surgical tracking systems, the uncertainty associated with the virtual model-to-physical phantom registration, as well as the uncertainty associated with live augmented reality (AR) views of the surgical scene achieved by enhancing the pre-procedural model and tracked surgical instrument views with live video views acquires using a camera tracked in real time. To better understand the effects of the tracked instrument calibration, registration fiducial configuration, and tracked camera calibration on the overall navigation uncertainty, we conducted Monte Carlo simulations that enabled us to identify optimal configurations that were subsequently validated experimentally using patient-specific phantoms in the laboratory. To mitigate the inherent accuracy limitations associated with the pre-procedural model-to-patient registration and their effect on the overall navigation, we also demonstrated the use of tracked video imaging to update the registration, enabling us to restore targeting accuracy to within its acceptable range. Lastly, we conducted several validation experiments using patient-specific kidney emulating phantoms using post-procedure CT imaging as reference ground truth to assess the accuracy of AR-guided navigation in the context of in vitro renal interventions. This work helped find answers to key questions about uncertainty propagation in image-guided renal interventions and led to the development of key techniques and tools to help reduce optimize the overall navigation / targeting uncertainty

TrauMAP - Integrating Anatomical and Physiological Simulation (Dissertation Proposal)

In trauma, many injuries impact anatomical structures, which may in turn affect physiological processes - not only those processes within the structure, but also ones occurring in physical proximity to them. Our goal with this research is to model mechanical interactions of different body systems and their impingement on underlying physiological processes. We are particularly concerned with pathological situations in which body system functions that normally do not interact become dependent as a result of mechanical behavior. Towards that end, the proposed TRAUMAP system (Trauma Modeling of Anatomy and Physiology) consists of three modules: (1) a hypothesis generator for suggesting possible structural changes that result from the direct injuries sustained; (2) an information source for responding to operator querying about anatomical structures, physiological processes, and pathophysiological processes; and (3) a continuous system simulator for simulating and illustrating anatomical and physiological changes in three dimensions. Models that can capture such changes may serve as an infrastructure for more detailed modeling and benefit surgical planning, surgical training, and general medical education, enabling students to visualize better, in an interactive environment, certain basic anatomical and physiological dependencies

Focal Spot, Winter 2006/2007

https://digitalcommons.wustl.edu/focal_spot_archives/1104/thumbnail.jp

Focal Spot, Summer 2003

https://digitalcommons.wustl.edu/focal_spot_archives/1094/thumbnail.jp