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Bram van Ginneken

Publications and source records attributed to Bram van Ginneken.

At least 73 records · Page 4Linked to original sources

FRODO: Free rejection of out-of-distribution samples: application to chest x-ray analysis

In this work, we propose a method to reject out-of-distribution samples which can be adapted to any network architecture and requires no additional training data. Publicly available chest x-ray data (38,353 images) is used to train a standard ResNet-50 model to detect emphysema. Feature activations of intermediate layers are used as descriptors defining the training data distribution. A novel metric, FRODO, is measured by using the Mahalanobis distance of a new test sample to the training data distribution. The method is tested using a held-out test dataset of 21,176 chest x-rays (in-distribution) and a set of 14,821 out-of-distribution x-ray images of incorrect orientation or anatomy. In classifying test samples as in or out-of distribution, our method achieves an AUC score of 0.99.

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Context Encoding Chest X-rays

Chest X-rays are one of the most commonly used technologies for medical diagnosis. Many deep learning models have been proposed to improve and automate the abnormality detection task on this type of data. In this paper, we propose a different approach based on image inpainting under adversarial training first introduced by Goodfellow et al. We configure the context encoder model for this task and train it over 1.1M 128x128 images from healthy X-rays. The goal of our model is to reconstruct the missing central 64x64 patch. Once the model has learned how to inpaint healthy tissue, we test its performance on images with and without abnormalities. We discuss and motivate our results considering PSNR, MSE and SSIM scores as evaluation metrics. In addition, we conduct a 2AFC observer study showing that in half of the times an expert is unable to distinguish real images from the ones reconstructed using our model. By computing and visualizing the pixel-wise difference between the source and the reconstructed images, we can highlight abnormalities to simplify further detection and classification tasks.

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Evaluation of a deep learning system for the joint automated detection of diabetic retinopathy and age-related macular degeneration

Purpose: To validate the performance of a commercially-available, CE-certified deep learning (DL) system, RetCAD v.1.3.0 (Thirona, Nijmegen, The Netherlands), for the joint automatic detection of diabetic retinopathy (DR) and age-related macular degeneration (AMD) in color fundus (CF) images on a dataset with mixed presence of eye diseases. Methods: Evaluation of joint detection of referable DR and AMD was performed on a DR-AMD dataset with 600 images acquired during routine clinical practice, containing referable and non-referable cases of both diseases. Each image was graded for DR and AMD by an experienced ophthalmologist to establish the reference standard (RS), and by four independent observers for comparison with human performance. Validation was furtherly assessed on Messidor (1200 images) for individual identification of referable DR, and the Age-Related Eye Disease Study (AREDS) dataset (133821 images) for referable AMD, against the corresponding RS. Results: Regarding joint validation on the DR-AMD dataset, the system achieved an area under the ROC curve (AUC) of 95.1% for detection of referable DR (SE=90.1%, SP=90.6%). For referable AMD, the AUC was 94.9% (SE=91.8%, SP=87.5%). Average human performance for DR was SE=61.5% and SP=97.8%; for AMD, SE=76.5% and SP=96.1%. Regarding detection of referable DR in Messidor, AUC was 97.5% (SE=92.0%, SP=92.1%); for referable AMD in AREDS, AUC was 92.7% (SE=85.8%, SP=86.0%). Conclusions: The validated system performs comparably to human experts at simultaneous detection of DR and AMD. This shows that DL systems can facilitate access to joint screening of eye diseases and become a quick and reliable support for ophthalmological experts.

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A large annotated medical image dataset for the development and evaluation of segmentation algorithms

Semantic segmentation of medical images aims to associate a pixel with a label in a medical image without human initialization. The success of semantic segmentation algorithms is contingent on the availability of high-quality imaging data with corresponding labels provided by experts. We sought to create a large collection of annotated medical image datasets of various clinically relevant anatomies available under open source license to facilitate the development of semantic segmentation algorithms. Such a resource would allow: 1) objective assessment of general-purpose segmentation methods through comprehensive benchmarking and 2) open and free access to medical image data for any researcher interested in the problem domain. Through a multi-institutional effort, we generated a large, curated dataset representative of several highly variable segmentation tasks that was used in a crowd-sourced challenge - the Medical Segmentation Decathlon held during the 2018 Medical Image Computing and Computer Aided Interventions Conference in Granada, Spain. Here, we describe these ten labeled image datasets so that these data may be effectively reused by the research community.

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Iterative fully convolutional neural networks for automatic vertebra segmentation and identification

Precise segmentation and anatomical identification of the vertebrae provides the basis for automatic analysis of the spine, such as detection of vertebral compression fractures or other abnormalities. Most dedicated spine CT and MR scans as well as scans of the chest, abdomen or neck cover only part of the spine. Segmentation and identification should therefore not rely on the visibility of certain vertebrae or a certain number of vertebrae. We propose an iterative instance segmentation approach that uses a fully convolutional neural network to segment and label vertebrae one after the other, independently of the number of visible vertebrae. This instance-by-instance segmentation is enabled by combining the network with a memory component that retains information about already segmented vertebrae. The network iteratively analyzes image patches, using information from both image and memory to search for the next vertebra. To efficiently traverse the image, we include the prior knowledge that the vertebrae are always located next to each other, which is used to follow the vertebral column. This method was evaluated with five diverse datasets, including multiple modalities (CT and MR), various fields of view and coverages of different sections of the spine, and a particularly challenging set of low-dose chest CT scans. The proposed iterative segmentation method compares favorably with state-of-the-art methods and is fast, flexible and generalizable.

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Epithelium segmentation using deep learning in H&E-stained prostate specimens with immunohistochemistry as reference standard

Prostate cancer (PCa) is graded by pathologists by examining the architectural pattern of cancerous epithelial tissue on hematoxylin and eosin (H&E) stained slides. Given the importance of gland morphology, automatically differentiating between glandular epithelial tissue and other tissues is an important prerequisite for the development of automated methods for detecting PCa. We propose a new method, using deep learning, for automatically segmenting epithelial tissue in digitized prostatectomy slides. We employed immunohistochemistry (IHC) to render the ground truth less subjective and more precise compared to manual outlining on H&E slides, especially in areas with high-grade and poorly differentiated PCa. Our dataset consisted of 102 tissue blocks, including both low and high grade PCa. From each block a single new section was cut, stained with H&E, scanned, restained using P63 and CK8/18 to highlight the epithelial structure, and scanned again. The H&E slides were co-registered to the IHC slides. On a subset of the IHC slides we applied color deconvolution, corrected stain errors manually, and trained a U-Net to perform segmentation of epithelial structures. Whole-slide segmentation masks generated by the IHC U-Net were used to train a second U-Net on H&E. Our system makes precise cell-level segmentations and segments both intact glands as well as individual (tumor) epithelial cells. We achieved an F1-score of 0.895 on a hold-out test set and 0.827 on an external reference set from a different center. We envision this segmentation as being the first part of a fully automated prostate cancer detection and grading pipeline.

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iW-Net: an automatic and minimalistic interactive lung nodule segmentation deep network

We propose iW-Net, a deep learning model that allows for both automatic and interactive segmentation of lung nodules in computed tomography images. iW-Net is composed of two blocks: the first one provides an automatic segmentation and the second one allows to correct it by analyzing 2 points introduced by the user in the nodule's boundary. For this purpose, a physics inspired weight map that takes the user input into account is proposed, which is used both as a feature map and in the system's loss function. Our approach is extensively evaluated on the public LIDC-IDRI dataset, where we achieve a state-of-the-art performance of 0.55 intersection over union vs the 0.59 inter-observer agreement. Also, we show that iW-Net allows to correct the segmentation of small nodules, essential for proper patient referral decision, as well as improve the segmentation of the challenging non-solid nodules and thus may be an important tool for increasing the early diagnosis of lung cancer.

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Chest X-ray Inpainting with Deep Generative Models

Generative adversarial networks have been successfully applied to inpainting in natural images. However, the current state-of-the-art models have not yet been widely adopted in the medical imaging domain. In this paper, we investigate the performance of three recently published deep learning based inpainting models: context encoders, semantic image inpainting, and the contextual attention model, applied to chest x-rays, as the chest exam is the most commonly performed radiological procedure. We train these generative models on 1.2M 128 $\times$ 128 patches from 60K healthy x-rays, and learn to predict the center 64 $\times$ 64 region in each patch. We test the models on both the healthy and abnormal radiographs. We evaluate the results by visual inspection and comparing the PSNR scores. The outputs of the models are in most cases highly realistic. We show that the methods have potential to enhance and detect abnormalities. In addition, we perform a 2AFC observer study and show that an experienced human observer performs poorly in detecting inpainted regions, particularly those generated by the contextual attention model.

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Student Beats the Teacher: Deep Neural Networks for Lateral Ventricles Segmentation in Brain MR

Ventricular volume and its progression are known to be linked to several brain diseases such as dementia and schizophrenia. Therefore accurate measurement of ventricle volume is vital for longitudinal studies on these disorders, making automated ventricle segmentation algorithms desirable. In the past few years, deep neural networks have shown to outperform the classical models in many imaging domains. However, the success of deep networks is dependent on manually labeled data sets, which are expensive to acquire especially for higher dimensional data in the medical domain. In this work, we show that deep neural networks can be trained on much-cheaper-to-acquire pseudo-labels (e.g., generated by other automated less accurate methods) and still produce more accurate segmentations compared to the quality of the labels. To show this, we use noisy segmentation labels generated by a conventional region growing algorithm to train a deep network for lateral ventricle segmentation. Then on a large manually annotated test set, we show that the network significantly outperforms the conventional region growing algorithm which was used to produce the training labels for the network. Our experiments report a Dice Similarity Coefficient (DSC) of $0.874$ for the trained network compared to $0.754$ for the conventional region growing algorithm ($p < 0.001$).

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Automatic calcium scoring in low-dose chest CT using deep neural networks with dilated convolutions

Heavy smokers undergoing screening with low-dose chest CT are affected by cardiovascular disease as much as by lung cancer. Low-dose chest CT scans acquired in screening enable quantification of atherosclerotic calcifications and thus enable identification of subjects at increased cardiovascular risk. This paper presents a method for automatic detection of coronary artery, thoracic aorta and cardiac valve calcifications in low-dose chest CT using two consecutive convolutional neural networks. The first network identifies and labels potential calcifications according to their anatomical location and the second network identifies true calcifications among the detected candidates. This method was trained and evaluated on a set of 1744 CT scans from the National Lung Screening Trial. To determine whether any reconstruction or only images reconstructed with soft tissue filters can be used for calcification detection, we evaluated the method on soft and medium/sharp filter reconstructions separately. On soft filter reconstructions, the method achieved F1 scores of 0.89, 0.89, 0.67, and 0.55 for coronary artery, thoracic aorta, aortic valve and mitral valve calcifications, respectively. On sharp filter reconstructions, the F1 scores were 0.84, 0.81, 0.64, and 0.66, respectively. Linearly weighted kappa coefficients for risk category assignment based on per subject coronary artery calcium were 0.91 and 0.90 for soft and sharp filter reconstructions, respectively. These results demonstrate that the presented method enables reliable automatic cardiovascular risk assessment in all low-dose chest CT scans acquired for lung cancer screening.

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Validation, comparison, and combination of algorithms for automatic detection of pulmonary nodules in computed tomography images: the LUNA16 challenge

Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems.

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A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.

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The importance of stain normalization in colorectal tissue classification with convolutional networks

The development of reliable imaging biomarkers for the analysis of colorectal cancer (CRC) in hematoxylin and eosin (H&E) stained histopathology images requires an accurate and reproducible classification of the main tissue components in the image. In this paper, we propose a system for CRC tissue classification based on convolutional networks (ConvNets). We investigate the importance of stain normalization in tissue classification of CRC tissue samples in H&E-stained images. Furthermore, we report the performance of ConvNets on a cohort of rectal cancer samples and on an independent publicly available dataset of colorectal H&E images.

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Towards automatic pulmonary nodule management in lung cancer screening with deep learning

The introduction of lung cancer screening programs will produce an unprecedented amount of chest CT scans in the near future, which radiologists will have to read in order to decide on a patient follow-up strategy. According to the current guidelines, the workup of screen-detected nodules strongly relies on nodule size and nodule type. In this paper, we present a deep learning system based on multi-stream multi-scale convolutional networks, which automatically classifies all nodule types relevant for nodule workup. The system processes raw CT data containing a nodule without the need for any additional information such as nodule segmentation or nodule size and learns a representation of 3D data by analyzing an arbitrary number of 2D views of a given nodule. The deep learning system was trained with data from the Italian MILD screening trial and validated on an independent set of data from the Danish DLCST screening trial. We analyze the advantage of processing nodules at multiple scales with a multi-stream convolutional network architecture, and we show that the proposed deep learning system achieves performance at classifying nodule type that surpasses the one of classical machine learning approaches and is within the inter-observer variability among four experienced human observers.

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Context-aware stacked convolutional neural networks for classification of breast carcinomas in whole-slide histopathology images

Automated classification of histopathological whole-slide images (WSI) of breast tissue requires analysis at very high resolutions with a large contextual area. In this paper, we present context-aware stacked convolutional neural networks (CNN) for classification of breast WSIs into normal/benign, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We first train a CNN using high pixel resolution patches to capture cellular level information. The feature responses generated by this model are then fed as input to a second CNN, stacked on top of the first. Training of this stacked architecture with large input patches enables learning of fine-grained (cellular) details and global interdependence of tissue structures. Our system is trained and evaluated on a dataset containing 221 WSIs of H&E stained breast tissue specimens. The system achieves an AUC of 0.962 for the binary classification of non-malignant and malignant slides and obtains a three class accuracy of 81.3% for classification of WSIs into normal/benign, DCIS, and IDC, demonstrating its potentials for routine diagnostics.

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Comparison of Different Methods for Tissue Segmentation in Histopathological Whole-Slide Images

Tissue segmentation is an important pre-requisite for efficient and accurate diagnostics in digital pathology. However, it is well known that whole-slide scanners can fail in detecting all tissue regions, for example due to the tissue type, or due to weak staining because their tissue detection algorithms are not robust enough. In this paper, we introduce two different convolutional neural network architectures for whole slide image segmentation to accurately identify the tissue sections. We also compare the algorithms to a published traditional method. We collected 54 whole slide images with differing stains and tissue types from three laboratories to validate our algorithms. We show that while the two methods do not differ significantly they outperform their traditional counterpart (Jaccard index of 0.937 and 0.929 vs. 0.870, p < 0.01).

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Transfer Learning for Domain Adaptation in MRI: Application in Brain Lesion Segmentation

Magnetic Resonance Imaging (MRI) is widely used in routine clinical diagnosis and treatment. However, variations in MRI acquisition protocols result in different appearances of normal and diseased tissue in the images. Convolutional neural networks (CNNs), which have shown to be successful in many medical image analysis tasks, are typically sensitive to the variations in imaging protocols. Therefore, in many cases, networks trained on data acquired with one MRI protocol, do not perform satisfactorily on data acquired with different protocols. This limits the use of models trained with large annotated legacy datasets on a new dataset with a different domain which is often a recurring situation in clinical settings. In this study, we aim to answer the following central questions regarding domain adaptation in medical image analysis: Given a fitted legacy model, 1) How much data from the new domain is required for a decent adaptation of the original network?; and, 2) What portion of the pre-trained model parameters should be retrained given a certain number of the new domain training samples? To address these questions, we conducted extensive experiments in white matter hyperintensity segmentation task. We trained a CNN on legacy MR images of brain and evaluated the performance of the domain-adapted network on the same task with images from a different domain. We then compared the performance of the model to the surrogate scenarios where either the same trained network is used or a new network is trained from scratch on the new dataset.The domain-adapted network tuned only by two training examples achieved a Dice score of 0.63 substantially outperforming a similar network trained on the same set of examples from scratch.

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Location Sensitive Deep Convolutional Neural Networks for Segmentation of White Matter Hyperintensities

The anatomical location of imaging features is of crucial importance for accurate diagnosis in many medical tasks. Convolutional neural networks (CNN) have had huge successes in computer vision, but they lack the natural ability to incorporate the anatomical location in their decision making process, hindering success in some medical image analysis tasks. In this paper, to integrate the anatomical location information into the network, we propose several deep CNN architectures that consider multi-scale patches or take explicit location features while training. We apply and compare the proposed architectures for segmentation of white matter hyperintensities in brain MR images on a large dataset. As a result, we observe that the CNNs that incorporate location information substantially outperform a conventional segmentation method with hand-crafted features as well as CNNs that do not integrate location information. On a test set of 46 scans, the best configuration of our networks obtained a Dice score of 0.791, compared to 0.797 for an independent human observer. Performance levels of the machine and the independent human observer were not statistically significantly different (p-value=0.17).

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