New approaches to automated annotation of pathology-level findings in brain images DINH THIEN ANH Bachelor of Computing National University of Singapore A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY SCHOOL OF COMPUTING NATIONAL UNIVERSITY OF SINGAPORE 2013 Acknowledgements First and foremost, I would like to express my deepest gratitude to my thesis advisor, Dr. Tze-Yun Leong, for her incisive guidance, encouragement, patience and immense support through out my Ph.D career. And I have learned a lot from her. She has also provided me with an excellent research environment that is full of freedom. Without her help and belief, I would not have finished my dissertation. I am very grateful to have Dr. Choie Cheio Tchoyoson Lim from National Neuroscience Institute as my medical advisor. Despite his extremely busy schedule, he is always available to share with me his valuable medical knowledge and insightful feedbacks for my research. In addition, thanks to his generous reference, I have the honor to receive the Singapore Millennium Scholarship for my graduate study. I am also much indebted to Dr. Tomi Silander for being such an excellent mentor and for his inputs in my research. He has helped me to overcome so many obstacles in my research. Together with Dr. Tze Yun Leong, he has reviewed my thesis and provided many thoughtful suggestions, which help me to improve this thesis tremendously. I cannot thank him enough for his devotion. And I have also benefited so much from his wide knowledge and constructive advices. I am very fortunate to have several other mentors and collaborators along the way. I am thankful to Dr. Chew Lim Tan for his financial support which funded me as Research Assistant through the last year of my study. I would like to thank Dr. Boon Chuan Pang and Dr. Cheng Kiang Lee from National Neuroscience Institute for providing me the traumatic brain injury dataset. My sincere thank goes to Dr. Tianxia i Gong for providing me the labelled training dataset and her valuable experience in the medical imaging field. I wish to extend my thanks to Dr. Dinh Truong Huy Nguyen, Dr. Duc Hiep Chu, Thang Truong Duc, Dr. Bolan Su, Quang Loc Le, Thuy Ngoc Le, Thanh Trung Nguyen, Zhuoru Li, and many more great friends and colleagues through out the years for their friendship, ideas, encouragement and support. Without their accompanies, I would not have had that much fun in my life. My heartfelt gratitude goes to my fiance Ngoc Yen for her unconditional love, encouragement, patience, loyalty and for standing by me in both good and bad times. She has been virtually working as hard as me on this thesis. I am completely amazed at her willingness to proof read my writing countlessly. She is truly a gift that I am so blessed to have. Thank you dear from the bottom of my heart and I am looking forward to starting a family with you. Last but not least, I am extremely grateful to my parents for their unbounded love and sacrifice; and my elder brother and sister-in-law for their encouragement and understanding. My parents have been giving me many wonderful opportunities in life. I am forever thankful to have such an amazing family, and there is no word that can describe how much I love them. The past six years have been a bumpy ride for me. And their love, care, sacrifice, support and encouragement have made it become much easier. Thus, I owe this to my family. ii Table of Contents Introduction 1.1 Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Approaches and contributions . . . . . . . . . . . . . . . . . . . . . 1.3 Problem formulation . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Road map of this thesis . . . . . . . . . . . . . . . . . . . . . . . . . The medical domains 11 2.1 Ischemic stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.1.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.1.2 Related work . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Traumatic brain injury . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.2.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.2.2 Related work . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2.2 2.3 An overview of the pathology-level medical image annotation system 19 3.1 Feature extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.2 Modelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.3 Annotation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.4 Evaluation metrics . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Related work 27 4.1 27 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii 4.2 4.3 4.4 4.5 4.1.1 Generative models vs. Discriminative models . . . . . . . . . 27 4.1.2 Ensemble learning . . . . . . . . . . . . . . . . . . . . . . . 29 Feature extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 4.2.1 Global features . . . . . . . . . . . . . . . . . . . . . . . . . 31 4.2.2 Local features . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Annotating natural images . . . . . . . . . . . . . . . . . . . . . . . 33 4.3.1 Translation paradigm . . . . . . . . . . . . . . . . . . . . . . 34 4.3.2 Relevance Models . . . . . . . . . . . . . . . . . . . . . . . 35 4.3.3 Other approaches . . . . . . . . . . . . . . . . . . . . . . . . 35 4.3.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Annotating medical images . . . . . . . . . . . . . . . . . . . . . . . 38 4.4.1 Organ-level annotation . . . . . . . . . . . . . . . . . . . . . 39 4.4.2 Pathology-level annotation . . . . . . . . . . . . . . . . . . . 40 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 A generative model based approach 43 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 5.2 Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 5.3 Image Processing Component . . . . . . . . . . . . . . . . . . . . . 46 5.3.1 Automated lesion segmentation . . . . . . . . . . . . . . . . 47 5.3.2 Feature Extraction . . . . . . . . . . . . . . . . . . . . . . . 48 5.4 Generative model . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.5 Content-based retrieval . . . . . . . . . . . . . . . . . . . . . . . . . 56 5.6 Result . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 5.7 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 5.8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 A discriminative-model based approach 61 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 6.2 Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 6.3 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 6.3.1 65 Feature extraction component . . . . . . . . . . . . . . . . . iv 6.3.2 Classification system . . . . . . . . . . . . . . . . . . . . . . 66 Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 6.4.1 Without global features . . . . . . . . . . . . . . . . . . . . . 74 6.4.2 With global features . . . . . . . . . . . . . . . . . . . . . . 76 6.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 6.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 6.4 Unsupervised classification by combining case-based classifiers 81 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 7.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 7.2.1 System architecture . . . . . . . . . . . . . . . . . . . . . . . 84 7.2.2 Gabor feature extraction . . . . . . . . . . . . . . . . . . . . 84 7.2.3 Sparse representation-based classifier . . . . . . . . . . . . . 87 7.2.4 Ensemble of weak classifiers . . . . . . . . . . . . . . . . . . 89 Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 7.3.1 Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 7.3.2 Experimental setup . . . . . . . . . . . . . . . . . . . . . . . 92 7.3.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 7.3 7.4 Automatic Traumatic Brain Injury prognosis 99 8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 8.2 Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 8.3 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 8.3.1 Preprocessing and feature extraction . . . . . . . . . . . . . . 103 8.3.2 Classification of CT image slices . . . . . . . . . . . . . . . . 104 8.4 Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 8.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 8.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 Prototype implementation and informal evaluation 9.1 113 Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 v 9.1.1 GUI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 9.1.2 Annotator . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 9.2 Informal evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 9.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 10 Conclusion 121 10.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 10.2 Proposed approaches and contributions . . . . . . . . . . . . . . . . . 122 10.2.1 The generative model based approach . . . . . . . . . . . . . 122 10.2.2 The discriminative model based approach . . . . . . . . . . . 123 10.2.3 The unsupervised classification by combining case-based classifiers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 10.3 Future work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 vi Summary Medical image annotation aims to improve the e↵ectiveness and efficiency of keywordbased image retrieval. In this work, we focus on automated pathology annotation that tries to identify potential pathologies, abnormalities and diseases from brain images. This is a challenging task because pathology annotation demands a deep understanding of the structural and functional changes induced by diseases. Existing works in pathological annotation often require large and fully annotated training data, reliable segmentation, and domain knowledge for hand-crafted feature extraction and selection. Since these prerequisites are not always feasible, they reduce the level of automation, desirability, and practicality of the annotation systems. To mitigate the requirements of annotated training data and reliable segmentation, we propose to use probabilistic generative models, since they support the integration of expert knowledge and e↵ectively handle the uncertainties inherent in the images and segmentation. However, when a priori knowledge is not available, these generative models are not able to achieve their best performance. In this case, we suggest using a discriminative model which incorporates an automated feature selection method to tackle the problem. Specifically, sparse group lasso provides a flexible selection mechanism that helps to handle annotation problems without relying on the domain knowledge. The performance of existing annotation methods heavily depends on the quality of hand-crafted features extracted from an automatic image segmentation. To achieve good performance, constructing the system requires a considerable amount of manual work. We propose to combine an unsupervised feature extraction technique with a case-based classification in an ensemble learning framework to improve the adaptability and automation of the annotation systems. The unsupervised nature of this non-parametric technique can significantly reduce the time and e↵ort for system calibration. To evaluate these approaches, we select two important neurological disorders - ischemic stroke and traumatic brain injury, as illustrative domains because imaging findings of these diseases play significant roles in their diagnosis. Despite the additional challenges due to the relaxation of the common prerequisites in existing systems, our vii proposed frameworks still show reasonable performance. An informal evaluation with expert users has also demonstrated the practical promise of the proposed system. viii Chapter 10 Conclusion We conclude by reflecting on the lessons learned from this research. We summarize the contributions of this work and compare our approaches with related work. Finally, we discuss some directions for future research. 10.1 Summary We began with the comparison of existing methodologies for addressing a subclass of medical image annotation problems. We identified that generative models, discriminative models and ensemble learning are three common bases of the current techniques. Building on these common bases and integrating di↵erent features of these techniques, we proposed three novel approaches for annotating pathology-level information in medical images. To evaluate the feasibility and e↵ectiveness of these approaches, we implemented them in two important medical imaging domains: ischemic stroke and traumatic brain injury. In addition, we found that pathology-level annotation techniques can be used for a clinical outcome prediction. We also conducted an informal evaluation of the prototype system of one of our proposed methods. This exercise demonstrated the practical promise of the overall framework. 121 10.2 Proposed approaches and contributions In pathology-level image annotation, many existing systems operate under several prerequisite conditions which limit their automation, robustness and practicality. The first prerequisite is to have annotated training data. Although medical images are abundant, annotated training data is rare because it is labour-intensive and time-consuming to annotate them. Secondly, existing frameworks often require accurate segmentation results. The inability of the systems to deal with imperfect segmentation results restricts their usability in practice. Moreover, automated segmentation techniques still require a considerable amount of manual calibration work. Third, domain knowledge is required for hand-crafted feature extraction and selection. However, such prior knowledge is not always available. Lastly, the availability of large training dataset is often assumed. The main contributions of our proposed approaches is to improve the automation and practicality of existing pathology image annotation systems by relaxing some of the assumptions or prerequisites mentioned above. We proposed three novel approaches to pathology annotation of brain images. 10.2.1 The generative model based approach To address the issues with the lack of annotated training data and reliable segmentation, we propose using the probabilistic generative model which naturally supports the incorporation of an expert knowledge and e↵ectively handles the uncertainties inherent in the images and image segmentation. Unlike existing generative image annotation methods based on the translation paradigm [87, 29, 7], the relevance models [51, 33] and the closely related method by Carneiro et al. [13], the proposed model can capture spatial constraints among abnormal findings in an image, which are essential in identifying diseases and disorders and ruling out artifacts. Furthermore, since these techniques usually require a large training dataset for model construction, they 122 are not suitable for dealing with small training medical image dataset. Our empirical study demonstrates the feasibility of building a pathology-level annotation system with a limited training dataset. This proposed solution is also the first attempt to perform subtype annotation in the ischemic stroke domain. 10.2.2 The discriminative model based approach Di↵erent from the generative model approach, the discriminative model with an automated feature selection can avoid the dependency on prior knowledge. When the domain knowledge is not available, our framework that adopts the sparse group lasso feature selection technique and the SVM can achieve better performance. Similar to the generative model, fully annotated training data and perfect segmentation results for the relevant brain regions are optional. In addition, the sparse group lasso provides a flexible selection mechanism to capture the structure of the dataset. We have also combined both region-based features and global features in our model. Since existing works [21, 70, 115] only handle annotating regions of interests (ROI) from CT brain images, the main highlight of the proposed method is to work directly with a CT brain scan. Comparing our method with the state-of-the-art approach in classifying ROIs [37], our classifier has demonstrated very encouraging results. 10.2.3 The unsupervised classification by combining case-based classifiers The performance of existing methods often depends on the quality of hand-crafted features extracted from automatic image segmentation. Therefore, extracting useful features and calibrating automatic segmentation heavily depend on manual work. We have presented an ensemble classification framework with sparse Gabor-feature based classifiers to tackle these limitations. By doing so, we can achieve an automated and robust image annotation system. In comparing with the most recent methods in 123 annotating TBI images [38], we have obtained reasonable results without relying on a time-consuming process of manually selecting handcrafted features. We further extend the unsupervised method to deal with 3-D brain images. Unlike many previous methods [20, 99] which require expensive and time-consuming manual interpretation of the original brain images, the proposed method automatically predicts an outcome of a CT scan using only weakly labelled training data. As a result, it is suitable for classifying large brain image datasets. In an initial human evaluation, senior radiologists found the accuracy of the automated prognosis to be potentially useful in practice. Although the above approaches are demonstrated in ischemic stroke and TBI images, they are also applicable to other brain imaging domains because no modalitydependent assumption is made in our work. However, there are open questions and technical limitations that have not been addressed in this dissertation. In the next section, we will discuss some potential directions that could further improve the proposed approaches. 10.3 Future work We identify five areas for improvement below. We often encounter the imbalance problem in medical domain, which means the critically ill patients normally constitute a small portion of the whole patient population. Imbalanced data often causes negative e↵ects on the performance of machine learning algorithms. In the scope of our work, this problem has not been addressed adequately. Existing techniques in tackling these problems such as SMOTE and modelbased sampling [15, 50] should be studied and incorporated into our proposed system. Second, one of the major problems in dealing with medical images is the lack of sufficient training data. Training an accurate model is a very challenging task. Therefore, incorporating textual information and metadata of medical images can help 124 to improve annotation accuracy. However, metadata is often captured in free text and subjective. How to integrate both visual information and textual information into a coherent annotation model could be a promising future direction. Third, in this work, the annotation process is done separately from the retrieval process. Hence, it could be inefficient for image retrieval. Ranking images within each category or concept has not been fully taken into account yet. While the previously proposed generative model can be conveniently converted into the retrieval system, it is more challenging for our methods based on discriminative approaches (Chapter 6) to achieve the same purpose [113]. Additional e↵orts should be put into studying this problem. The fourth issue is the lack of standard vocabulary and taxonomy for annotation. Currently, arbitrary vocabularies are being used. Hierarchical taxonomy and ontologies not only would standardize the annotation vocabulary but also make the annotation system more comprehensive for the image retrieval process. Last but not least, the predictive power of our annotation model could be enhanced by utilizing real-time feedback from the users in practice. Relevance feedback method [95] could be a good starting point in this direction. 125 126 Bibliography [1] Harold P Adams, Birgitte H Bendixen, L Jaap Kappelle, Jose Biller, Besty B Love, David Lee Gordon, Eugene E Marsh, and the TOAST Investigators. Classification of subtype of acute ischemic stroke. definitions for use in a multicenter clinical trial. toast. trial of org 10172 in acute stroke treatment. Stroke, 24(1):35–41, 1993. [2] Brian T Andrews, Bennie W Chiles III, Walter L Olsen, and Lawrence H Pitts. The e↵ect of intracerebral hematoma location on the risk of brain-stem compression and on clinical outcome. Journal of neurosurgery, 69(4):518–522, 1988. 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IEEE, 2007. 136 [...]... overview of the pathology- level medical image annotation system In this chapter, we describe a general framework for the pathology- level annotation of medical images The framework supports automated or semi -automated annotation of pathology- level information in input images The framework is able to handle images in 2-D or 3-D format and from di↵erent modalities (such as CT, MRI, X-ray) Annotated images. .. content, existing techniques for annotating natural images are not always suitable for annotating medical images As a result, automated annotation techniques for medical images need to be designed di↵erently There are two types of medical image annotation: organ -level annotation and pathology- level annotation Organ level annotation is the process of annotating general aspects of the images such as... training data size 1.4 Road map of this thesis The following is a road map of the remaining chapters of this thesis In Chapter 2, we discuss the domain knowledge and related work in ischemic stroke imaging and traumatic brain injury imaging In Chapter 3, we present the general framework of a pathology- level image annotation system In Chapter 4, we survey existing techniques in annotating natural and medical. .. (Figure 11) In stroke imaging, clinical imaging features are the abnormalities which often are the hyper intensive regions in the MRI images The objective of pathology annotation in ischemic stroke is to automatically annotate a 3-D MRI brain scan with its corresponding pathology class For instance, when small scatter lesions are observed in one vascular territory of a patient’s brain, the scan images can... have carefully examined the challenges in pathology- level annotation • We have proposed three novel approaches to existing unaddressed challenges of pathology- level annotation problem 7 • Our work provides a solid step toward improving the automation and practicality of existing pathology- level annotation systems • The proposed methods are evaluated into two important neurological domains, ischemic stroke... medical images Before going into the details of these techniques, we will briefly present the 9 strengths and weaknesses of three general machine learning approaches commonly used for these tasks, including discriminative models, generative models and ensemble learning We will then illustrate the common methods in annotating natural images and the challenges in applying to the medical imaging domain We... stroke subtype [57] The following are the main challenges in pathology annotation in this domain: 1 Semantic gap: The mapping between low -level image features and high -level image semantics is challenging in pathology annotation due to the complexity of the pathology A subtle change in the image could indicate a di↵erent pathological class Uncertainty and noise in the medical image feature extraction... framework consists of three main components: feature extraction, modelling and annotation (Figure 3-1) The life cycle of the annotation system can be divided into two di↵erent phases: 1) Training phase where training samples are used to construct modelling and annotation components and 2) Annotating phase where the system is actually used for annotating new images 19 Training' (volumetric)' images' Tes5ng'... attempt in an automated segmentation of stroke lesions from DWI images is introduced by Martel et al [81] They introduce a method of using the adaptive thresholding algorithm with spatial constraints for segmentation Matesin et al [82] apply seeded region growing algorithm and rule-based labeling to recognize brain lesions from CT images Usinskas et al [105] introduce an unsupervised classifier to identify... not only to ischemic stroke but also to other brain diseases or disorders (such as Traumatic brain injury) and in di↵erent image modalities (such as CT, MRI or X-ray) 1.2 Approaches and contributions The aim of this thesis is to propose solutions to the challenges of annotating medical images, especially of the brain, at the pathology level The annotation is guided by abnormalities found in the image . New approaches to automated annotation of pathology- level findings in brain images DINH THIEN ANH Bachelor of Computing National University of Singapore A THESIS SUBMITTED FOR THE DEGREE OF. designed di↵erently. There are two types of medical image annotation: organ -level annotation and pathology- level annotation. Organ level annotation is the process of annotating gen- eral aspects of the images such as. following are the main challenges in pathology annotation in this domain: 1. Semantic gap: The mapping between low -level image features and high -level image semantics is challenging in pathology annotation