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

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

Heterogeneous volumetric data mapping and its medical applications

With the advance of data acquisition techniques, massive solid geometries are being collected routinely in scientific tasks, these complex and unstructured data need to be effectively correlated for various processing and analysis. Volumetric mapping solves bijective low-distortion correspondence between/among 3D geometric data, and can serve as an important preprocessing step in many tasks in compute-aided design and analysis, industrial manufacturing, medical image analysis, to name a few. This dissertation studied two important volumetric mapping problems: the mapping of heterogeneous volumes (with nonuniform inner structures/layers) and the mapping of sequential dynamic volumes. To effectively handle heterogeneous volumes, first, we studied the feature-aligned harmonic volumetric mapping. Compared to previous harmonic mapping, it supports the point, curve, and iso-surface alignment, which are important low-dimensional structures in heterogeneous volumetric data. Second, we proposed a biharmonic model for volumetric mapping. Unlike the conventional harmonic volumetric mapping that only supports positional continuity on the boundary, this new model allows us to have higher order continuity $C^1$ along the boundary surface. This suggests a potential model to solve the volumetric mapping of complex and big geometries through divide-and-conquer. We also studied the medical applications of our volumetric mapping in lung tumor respiratory motion modeling. We were building an effective digital platform for lung tumor radiotherapy based on effective volumetric CT/MRI image matching and analysis. We developed and integrated in this platform a set of geometric/image processing techniques including advanced image segmentation, finite element meshing, volumetric registration and interpolation. The lung organ/tumor and surrounding tissues are treated as a heterogeneous region and a dynamic 4D registration framework is developed for lung tumor motion modeling and tracking. Compared to the previous 3D pairwise registration, our new 4D parameterization model leads to a significantly improved registration accuracy. The constructed deforming model can hence approximate the deformation of the tissues and tumor

Leveraging Supervoxels for Medical Image Volume Segmentation With Limited Supervision

The majority of existing methods for machine learning-based medical image segmentation are supervised models that require large amounts of fully annotated images. These types of datasets are typically not available in the medical domain and are difficult and expensive to generate. A wide-spread use of machine learning based models for medical image segmentation therefore requires the development of data-efficient algorithms that only require limited supervision. To address these challenges, this thesis presents new machine learning methodology for unsupervised lung tumor segmentation and few-shot learning based organ segmentation. When working in the limited supervision paradigm, exploiting the available information in the data is key. The methodology developed in this thesis leverages automatically generated supervoxels in various ways to exploit the structural information in the images. The work on unsupervised tumor segmentation explores the opportunity of performing clustering on a population-level in order to provide the algorithm with as much information as possible. To facilitate this population-level across-patient clustering, supervoxel representations are exploited to reduce the number of samples, and thereby the computational cost. In the work on few-shot learning-based organ segmentation, supervoxels are used to generate pseudo-labels for self-supervised training. Further, to obtain a model that is robust to the typically large and inhomogeneous background class, a novel anomaly detection-inspired classifier is proposed to ease the modelling of the background. To encourage the resulting segmentation maps to respect edges defined in the input space, a supervoxel-informed feature refinement module is proposed to refine the embedded feature vectors during inference. Finally, to improve trustworthiness, an architecture-agnostic mechanism to estimate model uncertainty in few-shot segmentation is developed. Results demonstrate that supervoxels are versatile tools for leveraging structural information in medical data when training segmentation models with limited supervision

Pulmonary Image Segmentation and Registration Algorithms: Towards Regional Evaluation of Obstructive Lung Disease

Pulmonary imaging, including pulmonary magnetic resonance imaging (MRI) and computed tomography (CT), provides a way to sensitively and regionally measure spatially heterogeneous lung structural-functional abnormalities. These unique imaging biomarkers offer the potential for better understanding pulmonary disease mechanisms, monitoring disease progression and response to therapy, and developing novel treatments for improved patient care. To generate these regional lung structure-function measurements and enable broad clinical applications of quantitative pulmonary MRI and CT biomarkers, as a first step, accurate, reproducible and rapid lung segmentation and registration methods are required. In this regard, we first developed a 1H MRI lung segmentation algorithm that employs complementary hyperpolarized 3He MRI functional information for improved lung segmentation. The 1H-3He MRI joint segmentation algorithm was formulated as a coupled continuous min-cut model and solved through convex relaxation, for which a dual coupled continuous max-flow model was proposed and a max-flow-based efficient numerical solver was developed. Experimental results on a clinical dataset of 25 chronic obstructive pulmonary disease (COPD) patients ranging in disease severity demonstrated that the algorithm provided rapid lung segmentation with high accuracy, reproducibility and diminished user interaction. We then developed a general 1H MRI left-right lung segmentation approach by exploring the left-to-right lung volume proportion prior. The challenging volume proportion-constrained multi-region segmentation problem was approximated through convex relaxation and equivalently represented by a max-flow model with bounded flow conservation conditions. This gave rise to a multiplier-based high performance numerical implementation based on convex optimization theories. In 20 patients with mild- to-moderate and severe asthma, the approach demonstrated high agreement with manual segmentation, excellent reproducibility and computational efficiency. Finally, we developed a CT-3He MRI deformable registration approach that coupled the complementary CT-1H MRI registration. The joint registration problem was solved by exploring optical-flow techniques, primal-dual analyses and convex optimization theories. In a diverse group of patients with asthma and COPD, the registration approach demonstrated lower target registration error than single registration and provided fast regional lung structure-function measurements that were strongly correlated with a reference method. Collectively, these lung segmentation and registration algorithms demonstrated accuracy, reproducibility and workflow efficiency that all may be clinically-acceptable. All of this is consistent with the need for broad and large-scale clinical applications of pulmonary MRI and CT

Minimally Interactive Segmentation with Application to Human Placenta in Fetal MR Images

Placenta segmentation from fetal Magnetic Resonance (MR) images is important for fetal surgical planning. However, accurate segmentation results are difficult to achieve for automatic methods, due to sparse acquisition, inter-slice motion, and the widely varying position and shape of the placenta among pregnant women. Interactive methods have been widely used to get more accurate and robust results. A good interactive segmentation method should achieve high accuracy, minimize user interactions with low variability among users, and be computationally fast. Exploiting recent advances in machine learning, I explore a family of new interactive methods for placenta segmentation from fetal MR images. I investigate the combination of user interactions with learning from a single image or a large set of images. For learning from a single image, I propose novel Online Random Forests to efficiently leverage user interactions for the segmentation of 2D and 3D fetal MR images. I also investigate co-segmentation of multiple volumes of the same patient with 4D Graph Cuts. For learning from a large set of images, I first propose a deep learning-based framework that combines user interactions with Convolutional Neural Networks (CNN) based on geodesic distance transforms to achieve accurate segmentation and good interactivity. I then propose image-specific fine-tuning to make CNNs adaptive to different individual images and able to segment previously unseen objects. Experimental results show that the proposed algorithms outperform traditional interactive segmentation methods in terms of accuracy and interactivity. Therefore, they might be suitable for segmentation of the placenta in planning systems for fetal and maternal surgery, and for rapid characterization of the placenta by MR images. I also demonstrate that they can be applied to the segmentation of other organs from 2D and 3D images

Feasibility and relevance of discrete vasculature modeling in routine hyperthermia treatment planning

Purpose: To investigate the effect of patient specific vessel cooling on head and neck hyperthermia treatment planning (HTP). Methods and materials: Twelve patients undergoing radiotherapy were scanned using computed tomography (CT), magnetic resonance imaging (MRI) and contrast enhanced MR angiography (CEMRA). 3D patient models were constructed using the CT and MRI data. The arterial vessel tree was constructed from the MRA images using the ‘graph-cut’ method, combining information from Frangi vesselness filtering and region growing, and the results were validated against manually placed markers in/outside the vessels. Patient specific HTP was performed and the change in thermal distribution prediction caused by arterial cooling was evaluated by adding discrete vasculature (DIVA) modeling to the Pennes bioheat equation (PBHE). Results: Inclusion of arterial cooling showed a relevant impact, i.e., DIVA modeling predicts a decreased treatment quality by on average 0.19 °C (T90), 0.32 °C (T50) and 0.35 °C (T20) that is robust against variations in the inflow blood rate (|ΔT| 0.5 °C) were observed. Conclusion: Addition of patient-specific DIVA into the thermal modeling can significantly change predicted treatment quality. In cases where clinically detectable vessels pass the heated region, we advise to perform DIVA modeling