An Alarm System For Segmentation Algorithm Based On Shape Model

It is usually hard for a learning system to predict correctly on rare events that never occur in the training data, and there is no exception for segmentation algorithms. Meanwhile, manual inspection of each case to locate the failures becomes infeasible due to the trend of large data scale and limited human resource. Therefore, we build an alarm system that will set off alerts when the segmentation result is possibly unsatisfactory, assuming no corresponding ground truth mask is provided. One plausible solution is to project the segmentation results into a low dimensional feature space; then learn classifiers/regressors to predict their qualities. Motivated by this, in this paper, we learn a feature space using the shape information which is a strong prior shared among different datasets and robust to the appearance variation of input data.The shape feature is captured using a Variational Auto-Encoder (VAE) network that trained with only the ground truth masks. During testing, the segmentation results with bad shapes shall not fit the shape prior well, resulting in large loss values. Thus, the VAE is able to evaluate the quality of segmentation result on unseen data, without using ground truth. Finally, we learn a regressor in the one-dimensional feature space to predict the qualities of segmentation results. Our alarm system is evaluated on several recent state-of-art segmentation algorithms for 3D medical segmentation tasks. Compared with other standard quality assessment methods, our system consistently provides more reliable prediction on the qualities of segmentation results.Comment: Accepted to ICCV 2019 (10 pages, 4 figures

Automated liver tissues delineation based on machine learning techniques: A survey, current trends and future orientations

There is no denying how machine learning and computer vision have grown in the recent years. Their highest advantages lie within their automation, suitability, and ability to generate astounding results in a matter of seconds in a reproducible manner. This is aided by the ubiquitous advancements reached in the computing capabilities of current graphical processing units and the highly efficient implementation of such techniques. Hence, in this paper, we survey the key studies that are published between 2014 and 2020, showcasing the different machine learning algorithms researchers have used to segment the liver, hepatic-tumors, and hepatic-vasculature structures. We divide the surveyed studies based on the tissue of interest (hepatic-parenchyma, hepatic-tumors, or hepatic-vessels), highlighting the studies that tackle more than one task simultaneously. Additionally, the machine learning algorithms are classified as either supervised or unsupervised, and further partitioned if the amount of works that fall under a certain scheme is significant. Moreover, different datasets and challenges found in literature and websites, containing masks of the aforementioned tissues, are thoroughly discussed, highlighting the organizers original contributions, and those of other researchers. Also, the metrics that are used excessively in literature are mentioned in our review stressing their relevancy to the task at hand. Finally, critical challenges and future directions are emphasized for innovative researchers to tackle, exposing gaps that need addressing such as the scarcity of many studies on the vessels segmentation challenge, and why their absence needs to be dealt with in an accelerated manner.Comment: 41 pages, 4 figures, 13 equations, 1 table. A review paper on liver tissues segmentation based on automated ML-based technique

腹部CT像上の複数オブジェクトのセグメンテーションのための統計的手法に関する研究

Computer aided diagnosis (CAD) is the use of a computer-generated output as an auxiliary tool for the assistance of efficient interpretation and accurate diagnosis. Medical image segmentation has an essential role in CAD in clinical applications. Generally, the task of medical image segmentation involves multiple objects, such as organs or diffused tumor regions. Moreover, it is very unfavorable to segment these regions from abdominal Computed Tomography (CT) images because of the overlap in intensity and variability in position and shape of soft tissues. In this thesis, a progressive segmentation framework is proposed to extract liver and tumor regions from CT images more efficiently, which includes the steps of multiple organs coarse segmentation, fine segmentation, and liver tumors segmentation. Benefit from the previous knowledge of the shape and its deformation, the Statistical shape model (SSM) method is firstly utilized to segment multiple organs regions robustly. In the process of building an SSM, the correspondence of landmarks is crucial to the quality of the model. To generate a more representative prototype of organ surface, a k-mean clustering method is proposed. The quality of the SSMs, which is measured by generalization ability, specificity, and compactness, was improved. We furtherly extend the shapes correspondence to multiple objects. A non-rigid iterative closest point surface registration process is proposed to seek more properly corresponded landmarks across the multi-organ surfaces. The accuracy of surface registration was improved as well as the model quality. Moreover, to localize the abdominal organs simultaneously, we proposed a random forest regressor cooperating intensity features to predict the position of multiple organs in the CT image. The regions of the organs are substantially restrained using the trained shape models. The accuracy of coarse segmentation using SSMs was increased by the initial information of organ positions.Consequently, a pixel-wise segmentation using the classification of supervoxels is applied for the fine segmentation of multiple organs. The intensity and spatial features are extracted from each supervoxels and classified by a trained random forest. The boundary of the supervoxels is closer to the real organs than the previous coarse segmentation. Finally, we developed a hybrid framework for liver tumor segmentation in multiphase images. To deal with these issues of distinguishing and delineating tumor regions and peripheral tissues, this task is accomplished in two steps: a cascade region-based convolutional neural network (R-CNN) with a refined head is trained to locate the bounding boxes that contain tumors, and a phase-sensitive noise filtering is introduced to refine the following segmentation of tumor regions conducted by a level-set-based framework. The results of tumor detection show the adjacent tumors are successfully separated by the improved cascaded R-CNN. The accuracy of tumor segmentation is also improved by our proposed method. 26 cases of multi-phase CT images were used to validate our proposed method for the segmentation of liver tumors. The average precision and recall rates for tumor detection are 76.8% and 84.4%, respectively. The intersection over union, true positive rate, and false positive rate for tumor segmentation are 72.7%, 76.2%, and 4.75%, respectively.九州工業大学博士学位論文 学位記番号: 工博甲第546号 学位授与年月日: 令和4年3月25日1 Introduction|2 Literature Review|3 Statistical Shape Model Building|4 Multi-organ Segmentation|5 Liver Tumors Segmentation|6 Summary and Outlook九州工業大学令和3年

MEDICAL MACHINE INTELLIGENCE: DATA-EFFICIENCY AND KNOWLEDGE-AWARENESS

Traditional clinician diagnosis requires massive manual labor from experienced doctors, which is time-consuming and costly. Computer-aided systems are therefore proposed to reduce doctors’ efforts by using machines to automatically make diagnosis and treatment recommendations. The recent success in deep learning has largely advanced the field of computer-aided diagnosis by offering an avenue to deliver automated medical image analysis. Despite such progress, there remain several challenges towards medical machine intelligence, such as unsatisfactory performance regarding challenging small targets, insufficient training data, high annotation cost, the lack of domain-specific knowledge, etc. These challenges cultivate the need for developing data-efficient and knowledge-aware deep learning techniques which can generalize to different medical tasks without requiring intensive manual labeling efforts, and incorporate domain-specific knowledge in the learning process. In this thesis, we rethink the current progress of deep learning in medical image analysis, with a focus on the aforementioned challenges, and present different data-efficient and knowledge-aware deep learning approaches to address them accordingly. Firstly, we introduce coarse-to-fine mechanisms which use the prediction from the first (coarse) stage to shrink the input region for the second (fine) stage, to enhance the model performance especially for segmenting small challenging structures, such as the pancreas which occupies only a very small fraction (e.g., < 0.5%) of the entire CT volume. The method achieved the state-of-the-art result on the NIH pancreas segmentation dataset. Further extensions also demonstrated effectiveness for segmenting neoplasms such as pancreatic cysts or multiple organs. Secondly, we present a semi-supervised learning framework for medical image segmentation by leveraging both limited labeled data and abundant unlabeled data. Our learning method encourages the segmentation output to be consistent for the same input under different viewing conditions. More importantly, the outputs from different viewing directions are fused altogether to improve the quality of the target, which further enhances the overall performance. The comparison with fully-supervised methods on multi-organ segmentation confirms the effectiveness of this method. Thirdly, we discuss how to incorporate knowledge priors for multi-organ segmentation. Noticing that the abdominal organ sizes exhibit similar distributions across different cohorts, we propose to explicitly incorporate anatomical priors on abdominal organ sizes, guiding the training process with domain-specific knowledge. The approach achieves 84.97% on the MICCAI 2015 challenge “Multi-Atlas Labeling Beyond the Cranial Vault”, which significantly outperforms previous state-of-the-art even using fewer annotations. Lastly, by rethinking how radiologists interpret medical images, we identify one limitation for existing deep-learning-based works on detecting pancreatic ductal adenocarcinoma is the lack of knowledge integration from multi-phase images. Thereby, we introduce a dual-path network where different paths are connected for multi-phase information exchange, and an additional loss is added for removing view divergence. By effectively incorporating multi-phase information, the presented method shows superior performance than prior arts on this matter

Uncertainty Quantification in Biophotonic Imaging using Invertible Neural Networks

Owing to high stakes in the field of healthcare, medical machine learning (ML) applications have to adhere to strict safety standards. In particular, their performance needs to be robust toward volatile clinical inputs. The aim of the work presented in this thesis was to develop a framework for uncertainty handling in medical ML applications as a way to increase their robustness and trustworthiness. In particular, it addresses three root causes for lack of robustness that can be deemed central to the successful clinical translation of ML methods: First, many tasks in medical imaging can be phrased in the language of inverse problems. Most common ML methods aimed at solving such inverse problems implicitly assume that they are well-posed, especially that the problem has a unique solution. However, the solution might be ambiguous. In this thesis, we introduce a data-driven method for analyzing the well-posedness of inverse problems. In addition, we propose a framework to validate the suggested method in a problem-aware manner. Second, simulation is an important tool for the development of medical ML systems due to small in vivo data sets and/or a lack of annotated references (e. g. spatially resolved blood oxygenation (sO 2 )). However, simulation introduces a new uncertainty to the ML pipeline as ML performance guarantees generally rely on the testing data being sufficiently similar to the training data. This thesis addresses the uncertainty by quantifying the domain gap between training and testing data via an out-of-distribution (OoD) detection approach. Third, we introduce a new paradigm for medical ML based on personalized models. In a data-scarce regime with high inter-patient variability, classical ML models cannot be assumed to generalize well to new patients. To overcome this problem, we propose to train ML models on a per-patient basis. This approach circumvents the inter-patient variability, but it requires training without a supervision signal. We address this issue via OoD detection, where the current status quo is encoded as in-distribution (ID) using a personalized ML model. Changes to the status quo are then detected as OoD. While these three facets might seem distinct, the suggested framework provides a unified view of them. The enabling technology is the so-called invertible neural network (INN), which can be used as a flexible and expressive (conditional) density estimator. In this way, they can encode solutions to inverse problems as a probability distribution as well as tackle OoD detection tasks via density-based scores, like the widely applicable information criterion (WAIC). The present work validates our framework on the example of biophotonic imaging. Biophotonic imaging promises the estimation of tissue parameters such as sO 2 in a non-invasive way by evaluating the “fingerprint” of the tissue in the light spectrum. We apply our framework to analyze the well-posedness of the tissue parameter estimation problem at varying spectral and spatial resolutions. We find that with sufficient spectral and/or spatial context, the sO 2 estimation problem is well-posed. Furthermore, we examine the realism of simulated biophotonic data using the proposed OoD approach to gauge the generalization capabilities of our ML models to in vivo data. Our analysis shows a considerable remaining domain gap between the in silico and in vivo spectra. Lastly, we validate the personalized ML approach on the example of non-invasive ischemia monitoring in minimally invasive kidney surgery, for which we developed the first-in-human laparoscopic multispectral imaging system. In our study, we find a strong OoD signal between perfused and ischemic kidney spectra. Furthermore, the proposed approach is video-rate capable. In conclusion, we successfully developed a framework for uncertainty handling in medical ML and validated it using a diverse set of medical ML tasks, highlighting the flexibility and potential impact of our approach. The framework opens the door to robust solutions to applications like (recording) device design, quality control for simulation pipelines, and personalized video-rate tissue parameter monitoring. In this way, this thesis facilitates the development of the next generation of trustworthy ML systems in medicine

복부 CT에서 간과 혈관 분할 기법

학위논문(박사)--서울대학교 대학원 :공과대학 컴퓨터공학부,2020. 2. 신영길.복부 전산화 단층 촬영 (CT) 영상에서 정확한 간 및 혈관 분할은 체적 측정, 치료 계획 수립 및 추가적인 증강 현실 기반 수술 가이드와 같은 컴퓨터 진단 보조 시스템을 구축하는데 필수적인 요소이다. 최근 들어 컨볼루셔널 인공 신경망 (CNN) 형태의 딥 러닝이 많이 적용되면서 의료 영상 분할의 성능이 향상되고 있지만, 실제 임상에 적용할 수 있는 높은 일반화 성능을 제공하기는 여전히 어렵다. 또한 물체의 경계는 전통적으로 영상 분할에서 매우 중요한 요소로 이용되었지만, CT 영상에서 간의 불분명한 경계를 추출하기가 어렵기 때문에 현대 CNN에서는 이를 사용하지 않고 있다. 간 혈관 분할 작업의 경우, 복잡한 혈관 영상으로부터 학습 데이터를 만들기 어렵기 때문에 딥 러닝을 적용하기가 어렵다. 또한 얇은 혈관 부분의 영상 밝기 대비가 약하여 원본 영상에서 식별하기가 매우 어렵다. 본 논문에서는 위 언급한 문제들을 해결하기 위해 일반화 성능이 향상된 CNN과 얇은 혈관을 포함하는 복잡한 간 혈관을 정확하게 분할하는 알고리즘을 제안한다. 간 분할 작업에서 우수한 일반화 성능을 갖는 CNN을 구축하기 위해, 내부적으로 간 모양을 추정하는 부분이 포함된 자동 컨텍스트 알고리즘을 제안한다. 또한, CNN을 사용한 학습에 경계선의 개념이 새롭게 제안된다. 모호한 경계부가 포함되어 있어 전체 경계 영역을 CNN에 훈련하는 것은 매우 어렵기 때문에 반복되는 학습 과정에서 인공 신경망이 스스로 예측한 확률에서 부정확하게 추정된 부분적 경계만을 사용하여 인공 신경망을 학습한다. 실험적 결과를 통해 제안된 CNN이 다른 최신 기법들보다 정확도가 우수하다는 것을 보인다. 또한, 제안된 CNN의 일반화 성능을 검증하기 위해 다양한 실험을 수행한다. 간 혈관 분할에서는 간 내부의 관심 영역을 지정하기 위해 앞서 획득한 간 영역을 활용한다. 정확한 간 혈관 분할을 위해 혈관 후보 점들을 추출하여 사용하는 알고리즘을 제안한다. 확실한 후보 점들을 얻기 위해, 삼차원 영상의 차원을 먼저 최대 강도 투영 기법을 통해 이차원으로 낮춘다. 이차원 영상에서는 복잡한 혈관의 구조가 보다 단순화될 수 있다. 이어서, 이차원 영상에서 혈관 분할을 수행하고 혈관 픽셀들은 원래의 삼차원 공간상으로 역 투영된다. 마지막으로, 전체 혈관의 분할을 위해 원본 영상과 혈관 후보 점들을 모두 사용하는 새로운 레벨 셋 기반 알고리즘을 제안한다. 제안된 알고리즘은 복잡한 구조가 단순화되고 얇은 혈관이 더 잘 보이는 이차원 영상에서 얻은 후보 점들을 사용하기 때문에 얇은 혈관 분할에서 높은 정확도를 보인다. 실험적 결과에 의하면 제안된 알고리즘은 잘못된 영역의 추출 없이 다른 레벨 셋 기반 알고리즘들보다 우수한 성능을 보인다. 제안된 알고리즘은 간과 혈관을 분할하는 새로운 방법을 제시한다. 제안된 자동 컨텍스트 구조는 사람이 디자인한 학습 과정이 일반화 성능을 크게 향상할 수 있다는 것을 보인다. 그리고 제안된 경계선 학습 기법으로 CNN을 사용한 영상 분할의 성능을 향상할 수 있음을 내포한다. 간 혈관의 분할은 이차원 최대 강도 투영 기반 이미지로부터 획득된 혈관 후보 점들을 통해 얇은 혈관들이 성공적으로 분할될 수 있음을 보인다. 본 논문에서 제안된 알고리즘은 간의 해부학적 분석과 자동화된 컴퓨터 진단 보조 시스템을 구축하는 데 매우 중요한 기술이다.Accurate liver and its vessel segmentation on abdominal computed tomography (CT) images is one of the most important prerequisites for computer-aided diagnosis (CAD) systems such as volumetric measurement, treatment planning, and further augmented reality-based surgical guide. In recent years, the application of deep learning in the form of convolutional neural network (CNN) has improved the performance of medical image segmentation, but it is difficult to provide high generalization performance for the actual clinical practice. Furthermore, although the contour features are an important factor in the image segmentation problem, they are hard to be employed on CNN due to many unclear boundaries on the image. In case of a liver vessel segmentation, a deep learning approach is impractical because it is difficult to obtain training data from complex vessel images. Furthermore, thin vessels are hard to be identified in the original image due to weak intensity contrasts and noise. In this dissertation, a CNN with high generalization performance and a contour learning scheme is first proposed for liver segmentation. Secondly, a liver vessel segmentation algorithm is presented that accurately segments even thin vessels. To build a CNN with high generalization performance, the auto-context algorithm is employed. The auto-context algorithm goes through two pipelines: the first predicts the overall area of a liver and the second predicts the final liver using the first prediction as a prior. This process improves generalization performance because the network internally estimates shape-prior. In addition to the auto-context, a contour learning method is proposed that uses only sparse contours rather than the entire contour. Sparse contours are obtained and trained by using only the mispredicted part of the network's final prediction. Experimental studies show that the proposed network is superior in accuracy to other modern networks. Multiple N-fold tests are also performed to verify the generalization performance. An algorithm for accurate liver vessel segmentation is also proposed by introducing vessel candidate points. To obtain confident vessel candidates, the 3D image is first reduced to 2D through maximum intensity projection. Subsequently, vessel segmentation is performed from the 2D images and the segmented pixels are back-projected into the original 3D space. Finally, a new level set function is proposed that utilizes both the original image and vessel candidate points. The proposed algorithm can segment thin vessels with high accuracy by mainly using vessel candidate points. The reliability of the points can be higher through robust segmentation in the projected 2D images where complex structures are simplified and thin vessels are more visible. Experimental results show that the proposed algorithm is superior to other active contour models. The proposed algorithms present a new method of segmenting the liver and its vessels. The auto-context algorithm shows that a human-designed curriculum (i.e., shape-prior learning) can improve generalization performance. The proposed contour learning technique can increase the accuracy of a CNN for image segmentation by focusing on its failures, represented by sparse contours. The vessel segmentation shows that minor vessel branches can be successfully segmented through vessel candidate points obtained by reducing the image dimension. The algorithms presented in this dissertation can be employed for later analysis of liver anatomy that requires accurate segmentation techniques.Chapter 1 Introduction 1 1.1 Background and motivation 1 1.2 Problem statement 3 1.3 Main contributions 6 1.4 Contents and organization 9 Chapter 2 Related Works 10 2.1 Overview 10 2.2 Convolutional neural networks 11 2.2.1 Architectures of convolutional neural networks 11 2.2.2 Convolutional neural networks in medical image segmentation 21 2.3 Liver and vessel segmentation 37 2.3.1 Classical methods for liver segmentation 37 2.3.2 Vascular image segmentation 40 2.3.3 Active contour models 46 2.3.4 Vessel topology-based active contour model 54 2.4 Motivation 60 Chapter 3 Liver Segmentation via Auto-Context Neural Network with Self-Supervised Contour Attention 62 3.1 Overview 62 3.2 Single-pass auto-context neural network 65 3.2.1 Skip-attention module 66 3.2.2 V-transition module 69 3.2.3 Liver-prior inference and auto-context 70 3.2.4 Understanding the network 74 3.3 Self-supervising contour attention 75 3.4 Learning the network 81 3.4.1 Overall loss function 81 3.4.2 Data augmentation 81 3.5 Experimental Results 83 3.5.1 Overview 83 3.5.2 Data configurations and target of comparison 84 3.5.3 Evaluation metric 85 3.5.4 Accuracy evaluation 87 3.5.5 Ablation study 93 3.5.6 Performance of generalization 110 3.5.7 Results from ground-truth variations 114 3.6 Discussion 116 Chapter 4 Liver Vessel Segmentation via Active Contour Model with Dense Vessel Candidates 119 4.1 Overview 119 4.2 Dense vessel candidates 124 4.2.1 Maximum intensity slab images 125 4.2.2 Segmentation of 2D vessel candidates and back-projection 130 4.3 Clustering of dense vessel candidates 135 4.3.1 Virtual gradient-assisted regional ACM 136 4.3.2 Localized regional ACM 142 4.4 Experimental results 145 4.4.1 Overview 145 4.4.2 Data configurations and environment 146 4.4.3 2D segmentation 146 4.4.4 ACM comparisons 149 4.4.5 Evaluation of bifurcation points 154 4.4.6 Computational performance 159 4.4.7 Ablation study 160 4.4.8 Parameter study 162 4.5 Application to portal vein analysis 164 4.6 Discussion 168 Chapter 5 Conclusion and Future Works 170 Bibliography 172 초록 197Docto

Generative-Discriminative Low Rank Decomposition for Medical Imaging Applications

In this thesis, we propose a method that can be used to extract biomarkers from medical images toward early diagnosis of abnormalities. Surge of demand for biomarkers and availability of medical images in the recent years call for accurate, repeatable, and interpretable approaches for extracting meaningful imaging features. However, extracting such information from medical images is a challenging task because the number of pixels (voxels) in a typical image is in order of millions while even a large sample-size in medical image dataset does not usually exceed a few hundred. Nevertheless, depending on the nature of an abnormality, only a parsimonious subset of voxels is typically relevant to the disease; therefore various notions of sparsity are exploited in this thesis to improve the generalization performance of the prediction task. We propose a novel discriminative dimensionality reduction method that yields good classification performance on various datasets without compromising the clinical interpretability of the results. This is achieved by combining the modelling strength of generative learning framework and the classification performance of discriminative learning paradigm. Clinical interpretability can be viewed as an additional measure of evaluation and is also helpful in designing methods that account for the clinical prior such as association of certain areas in a brain to a particular cognitive task or connectivity of some brain regions via neural fibres. We formulate our method as a large-scale optimization problem to solve a constrained matrix factorization. Finding an optimal solution of the large-scale matrix factorization renders off-the-shelf solver computationally prohibitive; therefore, we designed an efficient algorithm based on the proximal method to address the computational bottle-neck of the optimization problem. Our formulation is readily extended for different scenarios such as cases where a large cohort of subjects has uncertain or no class labels (semi-supervised learning) or a case where each subject has a battery of imaging channels (multi-channel), \etc. We show that by using various notions of sparsity as feasible sets of the optimization problem, we can encode different forms of prior knowledge ranging from brain parcellation to brain connectivity

Automatic Pancreas Segmentation and 3D Reconstruction for Morphological Feature Extraction in Medical Image Analysis

The development of highly accurate, quantitative automatic medical image segmentation techniques, in comparison to manual techniques, remains a constant challenge for medical image analysis. In particular, segmenting the pancreas from an abdominal scan presents additional difficulties: this particular organ has very high anatomical variability, and a full inspection is problematic due to the location of the pancreas behind the stomach. Therefore, accurate, automatic pancreas segmentation can consequently yield quantitative morphological measures such as volume and curvature, supporting biomedical research to establish the severity and progression of a condition, such as type 2 diabetes mellitus. Furthermore, it can also guide subject stratification after diagnosis or before clinical trials, and help shed additional light on detecting early signs of pancreatic cancer. This PhD thesis delivers a novel approach for automatic, accurate quantitative pancreas segmentation in mostly but not exclusively Magnetic Resonance Imaging (MRI), by harnessing the advantages of machine learning and classical image processing in computer vision. The proposed approach is evaluated on two MRI datasets containing 216 and 132 image volumes, achieving a mean Dice similarity coefficient (DSC) of 84:1 4:6% and 85:7 2:3% respectively. In order to demonstrate the universality of the approach, a dataset containing 82 Computer Tomography (CT) image volumes is also evaluated and achieves mean DSC of 83:1 5:3%. The proposed approach delivers a contribution to computer science (computer vision) in medical image analysis, reporting better quantitative pancreas segmentation results in comparison to other state-of-the-art techniques, and also captures detailed pancreas boundaries as verified by two independent experts in radiology and radiography. The contributions’ impact can support the usage of computational methods in biomedical research with a clinical translation; for example, the pancreas volume provides a prognostic biomarker about the severity of type 2 diabetes mellitus. Furthermore, a generalisation of the proposed segmentation approach successfully extends to other anatomical structures, including the kidneys, liver and iliopsoas muscles using different MRI sequences. Thus, the proposed approach can incorporate into the development of a computational tool to support radiological interpretations of MRI scans obtained using different sequences by providing a “second opinion”, help reduce possible misdiagnosis, and consequently, provide enhanced guidance towards targeted treatment planning