Stacked fully convolutional networks with multi-channel learning: application to medical image segmentation

The automated segmentation of regions of interest (ROIs) in medical imaging is the fundamental requirement for the derivation of high-level semantics for image analysis in clinical decision support systems. Traditional segmentation approaches such as region-based depend heavily upon hand-crafted features and a priori knowledge of the user. As such, these methods are difficult to adopt within a clinical environment. Recently, methods based on fully convolutional networks (FCN) have achieved great success in the segmentation of general images. FCNs leverage a large labeled dataset to hierarchically learn the features that best correspond to the shallow appearance as well as the deep semantics of the images. However, when applied to medical images, FCNs usually produce coarse ROI detection and poor boundary definitions primarily due to the limited number of labeled training data and limited constraints of label agreement among neighboring similar pixels. In this paper, we propose a new stacked FCN architecture with multi-channel learning (SFCN-ML). We embed the FCN in a stacked architecture to learn the foreground ROI features and background non-ROI features separately and then integrate these different channels to produce the final segmentation result. In contrast to traditional FCN methods, our SFCN-ML architecture enables the visual attributes and semantics derived from both the fore- and background channels to be iteratively learned and inferred. We conducted extensive experiments on three public datasets with a variety of visual challenges. Our results show that our SFCN-ML is more effective and robust than a routine FCN and its variants, and other state-of-the-art methods

The Liver Tumor Segmentation Benchmark (LiTS)

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LITS) organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2016 and International Conference On Medical Image Computing Computer Assisted Intervention (MICCAI) 2017. Twenty four valid state-of-the-art liver and liver tumor segmentation algorithms were applied to a set of 131 computed tomography (CT) volumes with different types of tumor contrast levels (hyper-/hypo-intense), abnormalities in tissues (metastasectomie) size and varying amount of lesions. The submitted algorithms have been tested on 70 undisclosed volumes. The dataset is created in collaboration with seven hospitals and research institutions and manually reviewed by independent three radiologists. We found that not a single algorithm performed best for liver and tumors. The best liver segmentation algorithm achieved a Dice score of 0.96(MICCAI) whereas for tumor segmentation the best algorithm evaluated at 0.67(ISBI) and 0.70(MICCAI). The LITS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.Comment: conferenc

The Liver Tumor Segmentation Benchmark (LiTS)

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094

The Liver Tumor Segmentation Benchmark (LiTS)

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.Bjoern Menze is supported through the DFG funding (SFB 824, subproject B12) and a Helmut-Horten-Professorship for Biomedical Informatics by the Helmut-Horten-Foundation. Florian Kofler is Supported by Deutsche Forschungsgemeinschaft (DFG) through TUM International Graduate School of Science and Engineering (IGSSE), GSC 81. An Tang was supported by the Fonds de recherche du Québec en Santé and Fondation de l’association des radiologistes du Québec (FRQS- ARQ 34939 Clinical Research Scholarship – Junior 2 Salary Award). Hongwei Bran Li is supported by Forschungskredit (Grant NO. FK-21- 125) from University of Zurich.Peer ReviewedArticle signat per 109 autors/es: Patrick Bilic 1,a,b, Patrick Christ 1,a,b, Hongwei Bran Li 1,2,∗,b, Eugene Vorontsov 3,a,b, Avi Ben-Cohen 5,a, Georgios Kaissis 10,12,15,a, Adi Szeskin 18,a, Colin Jacobs 4,a, Gabriel Efrain Humpire Mamani 4,a, Gabriel Chartrand 26,a, Fabian Lohöfer 12,a, Julian Walter Holch 29,30,69,a, Wieland Sommer 32,a, Felix Hofmann 31,32,a, Alexandre Hostettler 36,a, Naama Lev-Cohain 38,a, Michal Drozdzal 34,a, Michal Marianne Amitai 35,a, Refael Vivanti 37,a, Jacob Sosna 38,a, Ivan Ezhov 1, Anjany Sekuboyina 1,2, Fernando Navarro 1,76,78, Florian Kofler 1,13,57,78, Johannes C. Paetzold 15,16, Suprosanna Shit 1, Xiaobin Hu 1, Jana Lipková 17, Markus Rempfler 1, Marie Piraud 57,1, Jan Kirschke 13, Benedikt Wiestler 13, Zhiheng Zhang 14, Christian Hülsemeyer 1, Marcel Beetz 1, Florian Ettlinger 1, Michela Antonelli 9, Woong Bae 73, Míriam Bellver 43, Lei Bi 61, Hao Chen 39, Grzegorz Chlebus 62,64, Erik B. Dam 72, Qi Dou 41, Chi-Wing Fu 41, Bogdan Georgescu 60, Xavier Giró-i-Nieto 45, Felix Gruen 28, Xu Han 77, Pheng-Ann Heng 41, Jürgen Hesser 48,49,50, Jan Hendrik Moltz 62, Christian Igel 72, Fabian Isensee 69,70, Paul Jäger 69,70, Fucang Jia 75, Krishna Chaitanya Kaluva 21, Mahendra Khened 21, Ildoo Kim 73, Jae-Hun Kim 53, Sungwoong Kim 73, Simon Kohl 69, Tomasz Konopczynski 49, Avinash Kori 21, Ganapathy Krishnamurthi 21, Fan Li 22, Hongchao Li 11, Junbo Li 8, Xiaomeng Li 40, John Lowengrub 66,67,68, Jun Ma 54, Klaus Maier-Hein 69,70,7, Kevis-Kokitsi Maninis 44, Hans Meine 62,65, Dorit Merhof 74, Akshay Pai 72, Mathias Perslev 72, Jens Petersen 69, Jordi Pont-Tuset 44, Jin Qi 56, Xiaojuan Qi 40, Oliver Rippel 74, Karsten Roth 47, Ignacio Sarasua 51,12, Andrea Schenk 62,63, Zengming Shen 59,60, Jordi Torres 46,43, Christian Wachinger 51,12,1, Chunliang Wang 42, Leon Weninger 74, Jianrong Wu 25, Daguang Xu 71, Xiaoping Yang 55, Simon Chun-Ho Yu 58, Yading Yuan 52, Miao Yue 20, Liping Zhang 58, Jorge Cardoso 9, Spyridon Bakas 19,23,24, Rickmer Braren 6,12,30,a, Volker Heinemann 33,a, Christopher Pal 3,a, An Tang 27,a, Samuel Kadoury 3,a, Luc Soler 36,a, Bram van Ginneken 4,a, Hayit Greenspan 5,a, Leo Joskowicz 18,a, Bjoern Menze 1,2,a // 1 Department of Informatics, Technical University of Munich, Germany; 2 Department of Quantitative Biomedicine, University of Zurich, Switzerland; 3 Ecole Polytechnique de Montréal, Canada; 4 Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands; 5 Department of Biomedical Engineering, Tel-Aviv University, Israel; 6 German Cancer Consortium (DKTK), Germany; 7 Pattern Analysis and Learning Group, Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; 8 Philips Research China, Philips China Innovation Campus, Shanghai, China; 9 School of Biomedical Engineering & Imaging Sciences, King’s College London, London, UK; 10 Institute for AI in Medicine, Technical University of Munich, Germany; 11 Department of Computer Science, Guangdong University of Foreign Studies, China; 12 Institute for diagnostic and interventional radiology, Klinikum rechts der Isar, Technical University of Munich, Germany; 13 Institute for diagnostic and interventional neuroradiology, Klinikum rechts der Isar,Technical University of Munich, Germany; 14 Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, China; 15 Department of Computing, Imperial College London, London, United Kingdom; 16 Institute for Tissue Engineering and Regenerative Medicine, Helmholtz Zentrum München, Neuherberg, Germany; 17 Brigham and Women’s Hospital, Harvard Medical School, USA; 18 School of Computer Science and Engineering, the Hebrew University of Jerusalem, Israel; 19 Center for Biomedical Image Computing and Analytics (CBICA), University of Pennsylvania, PA, USA; 20 CGG Services (Singapore) Pte. Ltd., Singapore; 21 Medical Imaging and Reconstruction Lab, Department of Engineering Design, Indian Institute of Technology Madras, India; 22 Sensetime, Shanghai, China; 23 Department of Radiology, Perelman School of Medicine, University of Pennsylvania, USA; 24 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA, USA; 25 Tencent Healthcare (Shenzhen) Co., Ltd, China; 26 The University of Montréal Hospital Research Centre (CRCHUM) Montréal, Québec, Canada; 27 Department of Radiology, Radiation Oncology and Nuclear Medicine, University of Montréal, Canada; 28 Institute of Control Engineering, Technische Universität Braunschweig, Germany; 29 Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; 30 Comprehensive Cancer Center Munich, Munich, Germany; 31 Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Germany; 32 Department of Radiology, University Hospital, LMU Munich, Germany; 33 Department of Hematology/Oncology & Comprehensive Cancer Center Munich, LMU Klinikum Munich, Germany; 34 Polytechnique Montréal, Mila, QC, Canada; 35 Department of Diagnostic Radiology, Sheba Medical Center, Tel Aviv university, Israel; 36 Department of Surgical Data Science, Institut de Recherche contre les Cancers de l’Appareil Digestif (IRCAD), France; 37 Rafael Advanced Defense System, Israel; 38 Department of Radiology, Hadassah University Medical Center, Jerusalem, Israel; 39 Department of Computer Science and Engineering, The Hong Kong University of Science and Technology, China; 40 Department of Electrical and Electronic Engineering, The University of Hong Kong, China; 41 Department of Computer Science and Engineering, The Chinese University of Hong Kong, Hong Kong, China; 42 Department of Biomedical Engineering and Health Systems, KTH Royal Institute of Technology, Sweden; 43 Barcelona Supercomputing Center, Barcelona, Spain; 44 Eidgenössische Technische Hochschule Zurich (ETHZ), Zurich, Switzerland; 45 Signal Theory and Communications Department, Universitat Politecnica de Catalunya, Catalonia, Spain; 46 Universitat Politecnica de Catalunya, Catalonia, Spain; 47 University of Tuebingen, Germany; 48 Mannheim Institute for Intelligent Systems in Medicine, department of Medicine Mannheim, Heidelberg University, Germany; 49 Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Germany; 50 Central Institute for Computer Engineering (ZITI), Heidelberg University, Germany; 51 Department of Child and Adolescent Psychiatry, Ludwig-Maximilians-Universität, Munich, Germany; 52 Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, NY, USA; 53 Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, South Korea; 54 Department of Mathematics, Nanjing University of Science and Technology, China; 55 Department of Mathematics, Nanjing University, China; 56 School of Information and Communication Engineering, University of Electronic Science and Technology of China, China; 57 Helmholtz AI, Helmholtz Zentrum München, Neuherberg, Germany; 58 Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Hong Kong, China; 59 Beckman Institute, University of Illinois at Urbana-Champaign, USA; 60 Siemens Healthineers, USA; 61 School of Computer Science, the University of Sydney, Australia; 62 Fraunhofer MEVIS, Bremen, Germany; 63 Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany; 64 Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands; 65 Medical Image Computing Group, FB3, University of Bremen, Germany; 66 Departments of Mathematics, Biomedical Engineering, University of California, Irvine, USA; 67 Center for Complex Biological Systems, University of California, Irvine, USA; 68 Chao Family Comprehensive Cancer Center, University of California, Irvine, USA; 69 Division of Medical Image Computing, German Cancer Research Center (DKFZ), Heidelberg, Germany; 70 Helmholtz Imaging, Germany; 71 NVIDIA, Santa Clara, CA, USA; 72 Department of Computer Science, University of Copenhagen, Denmark; 73 Kakao Brain, Republic of Korea; 74 Institute of Imaging & Computer Vision, RWTH Aachen University, Germany; 75 Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, China; 76 Department of Radiation Oncology and Radiotherapy, Klinikum rechts der Isar, Technical University of Munich, Germany; 77 Department of computer science, UNC Chapel Hill, USA; 78 TranslaTUM - Central Institute for Translational Cancer Research, Technical University of Munich, GermanyPostprint (published version

Incorporating Cardiac Substructures Into Radiation Therapy For Improved Cardiac Sparing

Growing evidence suggests that radiation therapy (RT) doses to the heart and cardiac substructures (CS) are strongly linked to cardiac toxicities, though only the heart is considered clinically. This work aimed to utilize the superior soft-tissue contrast of magnetic resonance (MR) to segment CS, quantify uncertainties in their position, assess their effect on treatment planning and an MR-guided environment. Automatic substructure segmentation of 12 CS was completed using a novel hybrid MR/computed tomography (CT) atlas method and was improved upon using a 3-dimensional neural network (U-Net) from deep learning. Intra-fraction motion due to respiration was then quantified. The inter-fraction setup uncertainties utilizing a novel MR-linear accelerator were also quantified. Treatment planning comparisons were performed with and without substructure inclusions and methods to reduce radiation dose to sensitive CS were evaluated. Lastly, these described technologies (deep learning U-Net) were translated to an MR-linear accelerator and a segmentation pipeline was created. Automatic segmentations from the hybrid MR/CT atlas was able to generate accurate segmentations for the chambers and great vessels (Dice similarity coefficient (DSC) \u3e 0.75) but coronary artery segmentations were unsuccessful (DSC\u3c0.3). After implementing deep learning, DSC for the chambers and great vessels was ≥0.85 along with an improvement in the coronary arteries (DSC\u3e0.5). Similar accuracy was achieved when implementing deep learning for MR-guided RT. On average, automatic segmentations required ~10 minutes to generate per patient and deep learning only required 14 seconds. The inclusion of CS in the treatment planning process did not yield statistically significant changes in plan complexity, PTV, or OAR dose. Automatic segmentation results from deep learning pose major efficiency and accuracy gains for CS segmentation offering high potential for rapid implementation into radiation therapy planning for improved cardiac sparing. Introducing CS into RT planning for MR-guided RT presented an opportunity for more effective sparing with limited increase in plan complexity

Incorporating Cardiac Substructures Into Radiation Therapy For Improved Cardiac Sparing

Growing evidence suggests that radiation therapy (RT) doses to the heart and cardiac substructures (CS) are strongly linked to cardiac toxicities, though only the heart is considered clinically. This work aimed to utilize the superior soft-tissue contrast of magnetic resonance (MR) to segment CS, quantify uncertainties in their position, assess their effect on treatment planning and an MR-guided environment. Automatic substructure segmentation of 12 CS was completed using a novel hybrid MR/computed tomography (CT) atlas method and was improved upon using a 3-dimensional neural network (U-Net) from deep learning. Intra-fraction motion due to respiration was then quantified. The inter-fraction setup uncertainties utilizing a novel MR-linear accelerator were also quantified. Treatment planning comparisons were performed with and without substructure inclusions and methods to reduce radiation dose to sensitive CS were evaluated. Lastly, these described technologies (deep learning U-Net) were translated to an MR-linear accelerator and a segmentation pipeline was created. Automatic segmentations from the hybrid MR/CT atlas was able to generate accurate segmentations for the chambers and great vessels (Dice similarity coefficient (DSC) \u3e 0.75) but coronary artery segmentations were unsuccessful (DSC\u3c0.3). After implementing deep learning, DSC for the chambers and great vessels was ≥0.85 along with an improvement in the coronary arteries (DSC\u3e0.5). Similar accuracy was achieved when implementing deep learning for MR-guided RT. On average, automatic segmentations required ~10 minutes to generate per patient and deep learning only required 14 seconds. The inclusion of CS in the treatment planning process did not yield statistically significant changes in plan complexity, PTV, or OAR dose. Automatic segmentation results from deep learning pose major efficiency and accuracy gains for CS segmentation offering high potential for rapid implementation into radiation therapy planning for improved cardiac sparing. Introducing CS into RT planning for MR-guided RT presented an opportunity for more effective sparing with limited increase in plan complexity

Domain Generalization in Computational Pathology: Survey and Guidelines

Deep learning models have exhibited exceptional effectiveness in Computational Pathology (CPath) by tackling intricate tasks across an array of histology image analysis applications. Nevertheless, the presence of out-of-distribution data (stemming from a multitude of sources such as disparate imaging devices and diverse tissue preparation methods) can cause \emph{domain shift} (DS). DS decreases the generalization of trained models to unseen datasets with slightly different data distributions, prompting the need for innovative \emph{domain generalization} (DG) solutions. Recognizing the potential of DG methods to significantly influence diagnostic and prognostic models in cancer studies and clinical practice, we present this survey along with guidelines on achieving DG in CPath. We rigorously define various DS types, systematically review and categorize existing DG approaches and resources in CPath, and provide insights into their advantages, limitations, and applicability. We also conduct thorough benchmarking experiments with 28 cutting-edge DG algorithms to address a complex DG problem. Our findings suggest that careful experiment design and CPath-specific Stain Augmentation technique can be very effective. However, there is no one-size-fits-all solution for DG in CPath. Therefore, we establish clear guidelines for detecting and managing DS depending on different scenarios. While most of the concepts, guidelines, and recommendations are given for applications in CPath, we believe that they are applicable to most medical image analysis tasks as well.Comment: Extended Versio

Data synthesis and adversarial networks: A review and meta-analysis in cancer imaging

Despite technological and medical advances, the detection, interpretation, and treatment of cancer based on imaging data continue to pose significant challenges. These include inter-observer variability, class imbalance, dataset shifts, inter- and intra-tumour heterogeneity, malignancy determination, and treatment effect uncertainty. Given the recent advancements in image synthesis, Generative Adversarial Networks (GANs), and adversarial training, we assess the potential of these technologies to address a number of key challenges of cancer imaging. We categorise these challenges into (a) data scarcity and imbalance, (b) data access and privacy, (c) data annotation and segmentation, (d) cancer detection and diagnosis, and (e) tumour profiling, treatment planning and monitoring. Based on our analysis of 164 publications that apply adversarial training techniques in the context of cancer imaging, we highlight multiple underexplored solutions with research potential. We further contribute the Synthesis Study Trustworthiness Test (SynTRUST), a meta-analysis framework for assessing the validation rigour of medical image synthesis studies. SynTRUST is based on 26 concrete measures of thoroughness, reproducibility, usefulness, scalability, and tenability. Based on SynTRUST, we analyse 16 of the most promising cancer imaging challenge solutions and observe a high validation rigour in general, but also several desirable improvements. With this work, we strive to bridge the gap between the needs of the clinical cancer imaging community and the current and prospective research on data synthesis and adversarial networks in the artificial intelligence community