Models, code, and papers for "Bram van Ginneken":

Automated Gleason Grading of Prostate Biopsies using Deep Learning

Jul 18, 2019
Wouter Bulten, Hans Pinckaers, Hester van Boven, Robert Vink, Thomas de Bel, Bram van Ginneken, Jeroen van der Laak, Christina Hulsbergen-van de Kaa, Geert Litjens

The Gleason score is the most important prognostic marker for prostate cancer patients but suffers from significant inter-observer variability. We developed a fully automated deep learning system to grade prostate biopsies. The system was developed using 5834 biopsies from 1243 patients. A semi-automatic labeling technique was used to circumvent the need for full manual annotation by pathologists. The developed system achieved a high agreement with the reference standard. In a separate observer experiment, the deep learning system outperformed 10 out of 15 pathologists. The system has the potential to improve prostate cancer prognostics by acting as a first or second reader.

* 13 pages, 6 figures 

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

Aug 17, 2018
Wouter Bulten, Péter Bándi, Jeffrey Hoven, Rob van de Loo, Johannes Lotz, Nick Weiss, Jeroen van der Laak, Bram van Ginneken, Christina Hulsbergen-van de Kaa, Geert Litjens

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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Streaming convolutional neural networks for end-to-end learning with multi-megapixel images

Nov 11, 2019
Hans Pinckaers, Bram van Ginneken, Geert Litjens

Due to memory constraints on current hardware, most convolution neural networks (CNN) are trained on sub-megapixel images. For example, most popular datasets in computer vision contain images much less than a megapixel in size (0.09MP for ImageNet and 0.001MP for CIFAR-10). In some domains such as medical imaging, multi-megapixel images are needed to identify the presence of disease accurately. We propose a novel method to directly train convolutional neural networks using any input image size end-to-end. This method exploits the locality of most operations in modern convolutional neural networks by performing the forward and backward pass on smaller tiles of the image. In this work, we show a proof of concept using images of up to 66-megapixels (8192x8192), saving approximately 50GB of memory per image. Using two public challenge datasets, we demonstrate that CNNs can learn to extract relevant information from these large images and benefit from increasing resolution. We improved the area under the receiver-operating characteristic curve from 0.580 (4MP) to 0.706 (66MP) for metastasis detection in breast cancer (CAMELYON17). We also obtained a Spearman correlation metric approaching state-of-the-art performance on the TUPAC16 dataset, from 0.485 (1MP) to 0.570 (16MP). Code to reproduce a subset of the experiments is available at

* In review 

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mlVIRNET: Multilevel Variational Image Registration Network

Sep 22, 2019
Alessa Hering, Bram van Ginneken, Stefan Heldmann

We present a novel multilevel approach for deep learning based image registration. Recently published deep learning based registration methods have shown promising results for a wide range of tasks. However, these algorithms are still limited to relatively small deformations. Our method addresses this shortcoming by introducing a multilevel framework, which computes deformation fields on different scales, similar to conventional methods. Thereby, a coarse-level alignment is obtained first, which is subsequently improved on finer levels. We demonstrate our method on the complex task of inhale-to-exhale lung registration. We show that the use of a deep learning multilevel approach leads to significantly better registration results.

* accepted for publication at MICCAI 2019 

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

Jul 02, 2019
Erdi Çallı, Keelin Murphy, Ecem Sogancioglu, Bram van Ginneken

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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Chest X-Rays Image Inpainting with Context Encoders

Dec 03, 2018
Davide Belli, Shi Hu, Ecem Sogancioglu, Bram van Ginneken

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 source and reconstructed images, we can highlight abnormalities to simplify further detection and classification tasks.

* 11 pages, 8 figures 

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Chest X-ray Inpainting with Deep Generative Models

Aug 29, 2018
Ecem Sogancioglu, Shi Hu, Davide Belli, Bram van Ginneken

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.

* 9 pages 

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Iterative augmentation of visual evidence for weakly-supervised lesion localization in deep interpretability frameworks

Oct 16, 2019
Cristina González-Gonzalo, Bart Liefers, Bram van Ginneken, Clara I. Sánchez

Interpretability of deep learning (DL) systems is gaining attention in medical imaging to increase experts' trust in the obtained predictions and facilitate their integration in clinical settings. We propose a deep visualization method to generate interpretability of DL classification tasks in medical imaging by means of visual evidence augmentation. The proposed method iteratively unveils abnormalities based on the prediction of a classifier trained only with image-level labels. For each image, initial visual evidence of the prediction is extracted with a given visual attribution technique. This provides localization of abnormalities that are then removed through selective inpainting. We iteratively apply this procedure until the system considers the image as normal. This yields augmented visual evidence, including less discriminative lesions which were not detected at first but should be considered for final diagnosis. We apply the method to grading of two retinal diseases in color fundus images: diabetic retinopathy (DR) and age-related macular degeneration (AMD). We evaluate the generated visual evidence and the performance of weakly-supervised localization of different types of DR and AMD abnormalities, both qualitatively and quantitatively. We show that the augmented visual evidence of the predictions highlights the biomarkers considered by the experts for diagnosis and improves the final localization performance. It results in a relative increase of 11.2$\pm$2.0% per image regarding average sensitivity per average 10 false positives, when applied to different classification tasks, visual attribution techniques and network architectures. This makes the proposed method a useful tool for exhaustive visual support of DL classifiers in medical imaging.

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Function Follows Form: Regression from Complete Thoracic Computed Tomography Scans

Sep 27, 2019
Max Argus, Cornelia Schaefer-Prokop, David A. Lynch, Bram van Ginneken

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality. While COPD diagnosis is based on lung function tests, early stages and progression of different aspects of the disease can be visible and quantitatively assessed on computed tomography (CT) scans. Many studies have been published that quantify imaging biomarkers related to COPD. In this paper we present a convolutional neural network that directly computes visual emphysema scores and predicts the outcome of lung function tests for 195 CT scans from the COPDGene study. Contrary to previous work, the proposed method does not encode any specific prior knowledge about what to quantify, but it is trained end-to-end with a set of 1424 CT scans for which the output parameters were available. The network provided state-of-the-art results for these tasks: Visual emphysema scores are comparable to those assessed by trained human observers; COPD diagnosis from estimated lung function reaches an area under the ROC curve of 0.94, outperforming prior art. The method is easily generalizable to other situations where information from whole scans needs to be summarized in single quantities.

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Iterative fully convolutional neural networks for automatic vertebra segmentation

Apr 12, 2018
Nikolas Lessmann, Bram van Ginneken, Pim A. de Jong, Ivana Išgum

Precise segmentation of the vertebrae is often required for automatic detection of vertebral abnormalities. This especially enables incidental detection of abnormalities such as compression fractures in images that were acquired for other diagnostic purposes. While many CT and MR scans of the chest and abdomen cover a section of the spine, they often do not cover the entire spine. Additionally, the first and last visible vertebrae are likely only partially included in such scans. In this paper, we therefore approach vertebra segmentation as an instance segmentation problem. A fully convolutional neural network is combined with an instance memory that retains information about already segmented vertebrae. This network iteratively analyzes image patches, using the instance memory to search for and segment the first not yet segmented vertebra. At the same time, each vertebra is classified as completely or partially visible, so that partially visible vertebrae can be excluded from further analyses. We evaluated this method on spine CT scans from a vertebra segmentation challenge and on low-dose chest CT scans. The method achieved an average Dice score of 95.8% and 92.1%, respectively, and a mean absolute surface distance of 0.194 mm and 0.344 mm.

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

Nov 30, 2018
Guilherme Aresta, Colin Jacobs, Teresa Araújo, António Cunha, Isabel Ramos, Bram van Ginneken, Aurélio Campilho

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.

* Pre-print submitted to IEEE Transactions on Biomedical Engineering 

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GANs for Medical Image Analysis

Sep 13, 2018
Salome Kazeminia, Christoph Baur, Arjan Kuijper, Bram van Ginneken, Nassir Navab, Shadi Albarqouni, Anirban Mukhopadhyay

Generative Adversarial Networks (GANs) and their extensions have carved open many exciting ways to tackle well known and challenging medical image analysis problems such as medical image denoising, reconstruction, segmentation, data simulation, detection or classification. Furthermore, their ability to synthesize images at unprecedented levels of realism also gives hope that the chronic scarcity of labeled data in the medical field can be resolved with the help of these generative models. In this review paper, a broad overview of recent literature on GANs for medical applications is given, the shortcomings and opportunities of the proposed methods are thoroughly discussed and potential future work is elaborated. A total of 63 papers published until end of July 2018 are reviewed. For quick access, the papers and important details such as the underlying method, datasets and performance are summarized in tables.

* Salome Kazeminia and Christoph Baur contributed equally to this work 

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

Mar 03, 2018
Mohsen Ghafoorian, Jonas Teuwen, Rashindra Manniesing, Frank-Erik de Leeuw, Bram van Ginneken, Nico Karssemeijer, Bram Platel

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 ($p < 0.001$).

* Proc. SPIE 10574, 105742U (2 March 2018) 
* 7 pages, 4 figures, SPIE Medical Imaging 2018 Conference paper 

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

Feb 01, 2018
Nikolas Lessmann, Bram van Ginneken, Majd Zreik, Pim A. de Jong, Bob D. de Vos, Max A. Viergever, Ivana Išgum

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.

* IEEE Transactions on Medical Imaging 37(2), pp 615-625, 2018 

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

Apr 03, 2017
Péter Bándi, Rob van de Loo, Milad Intezar, Daan Geijs, Francesco Ciompi, Bram van Ginneken, Jeroen van der Laak, Geert Litjens

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).

* Accepted for poster presentation at the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 

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

Mar 22, 2019
Cristina González-Gonzalo, Verónica Sánchez-Gutiérrez, Paula Hernández-Martínez, Inés Contreras, Yara T. Lechanteur, Artin Domanian, Bram van Ginneken, Clara I. Sánchez

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

May 10, 2017
Babak Ehteshami Bejnordi, Guido Zuidhof, Maschenka Balkenhol, Meyke Hermsen, Peter Bult, Bram van Ginneken, Nico Karssemeijer, Geert Litjens, Jeroen van der Laak

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

Oct 29, 2016
Mohsen Ghafoorian, Nico Karssemeijer, Tom Heskes, Inge van Uden, Clara Sanchez, Geert Litjens, Frank-Erik de Leeuw, Bram van Ginneken, Elena Marchiori, Bram Platel

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).

* 13 pages, 8 figures 

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

May 23, 2017
Francesco Ciompi, Oscar Geessink, Babak Ehteshami Bejnordi, Gabriel Silva de Souza, Alexi Baidoshvili, Geert Litjens, Bram van Ginneken, Iris Nagtegaal, Jeroen van der Laak

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.

* Published in Proceedings of IEEE International Symposium on Biomedical Imaging (ISBI) 2017 

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A deep learning model for segmentation of geographic atrophy to study its long-term natural history

Aug 15, 2019
Bart Liefers, Johanna M. Colijn, Cristina González-Gonzalo, Timo Verzijden, Paul Mitchell, Carel B. Hoyng, Bram van Ginneken, Caroline C. W. Klaver, Clara I. Sánchez

Purpose: To develop and validate a deep learning model for automatic segmentation of geographic atrophy (GA) in color fundus images (CFIs) and its application to study growth rate of GA. Participants: 409 CFIs of 238 eyes with GA from the Rotterdam Study (RS) and the Blue Mountain Eye Study (BMES) for model development, and 5,379 CFIs of 625 eyes from the Age-Related Eye Disease Study (AREDS) for analysis of GA growth rate. Methods: A deep learning model based on an ensemble of encoder-decoder architectures was implemented and optimized for the segmentation of GA in CFIs. Four experienced graders delineated GA in CFIs from RS and BMES. These manual delineations were used to evaluate the segmentation model using 5-fold cross-validation. The model was further applied to CFIs from the AREDS to study the growth rate of GA. Linear regression analysis was used to study associations between structural biomarkers at baseline and GA growth rate. A general estimate of the progression of GA area over time was made by combining growth rates of all eyes with GA from the AREDS set. Results: The model obtained an average Dice coefficient of 0.72 $\pm$ 0.26 on the BMES and RS. An intraclass correlation coefficient of 0.83 was reached between the automatically estimated GA area and the graders' consensus measures. Eight automatically calculated structural biomarkers (area, filled area, convex area, convex solidity, eccentricity, roundness, foveal involvement and perimeter) were significantly associated with growth rate. Combining all growth rates indicated that GA area grows quadratically up to an area of around 12 mm$^{2}$, after which growth rate stabilizes or decreases. Conclusion: The presented deep learning model allowed for fully automatic and robust segmentation of GA in CFIs. These segmentations can be used to extract structural characteristics of GA that predict its growth rate.

* 22 pages, 3 tables, 4 figures, 1 supplemental figure 

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