Lucas Fidon

Lucas Fidon, Michael Aertsen, Florian Kofler et al.

Deep learning models for medical image segmentation can fail unexpectedly and spectacularly for pathological cases and images acquired at different centers than training images, with labeling errors that violate expert knowledge. Such errors undermine the trustworthiness of deep learning models for medical image segmentation. Mechanisms for detecting and correcting such failures are essential for safely translating this technology into clinics and are likely to be a requirement of future regulations on artificial intelligence (AI). In this work, we propose a trustworthy AI theoretical framework and a practical system that can augment any backbone AI system using a fallback method and a fail-safe mechanism based on Dempster-Shafer theory. Our approach relies on an actionable definition of trustworthy AI. Our method automatically discards the voxel-level labeling predicted by the backbone AI that violate expert knowledge and relies on a fallback for those voxels. We demonstrate the effectiveness of the proposed trustworthy AI approach on the largest reported annotated dataset of fetal MRI consisting of 540 manually annotated fetal brain 3D T2w MRIs from 13 centers. Our trustworthy AI method improves the robustness of a state-of-the-art backbone AI for fetal brain MRIs acquired across various centers and for fetuses with various brain abnormalities.

Kelly Payette, Hongwei Li, Priscille de Dumast et al.

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.

Florian Kofler, Ivan Ezhov, Lucas Fidon et al.

Human ratings are abstract representations of segmentation quality. To approximate human quality ratings on scarce expert data, we train surrogate quality estimation models. We evaluate on a complex multi-class segmentation problem, specifically glioma segmentation, following the BraTS annotation protocol. The training data features quality ratings from 15 expert neuroradiologists on a scale ranging from 1 to 6 stars for various computer-generated and manual 3D annotations. Even though the networks operate on 2D images and with scarce training data, we can approximate segmentation quality within a margin of error comparable to human intra-rater reliability. Segmentation quality prediction has broad applications. While an understanding of segmentation quality is imperative for successful clinical translation of automatic segmentation quality algorithms, it can play an essential role in training new segmentation models. Due to the split-second inference times, it can be directly applied within a loss function or as a fully-automatic dataset curation mechanism in a federated learning setting.

Thiziri Nait Saada, Valentina Di Proietto, Benoit Schmauch et al.

Multiple Instance Learning (MIL) models have proven effective for cancer prognosis from Whole Slide Images. However, the original MIL formulation incorrectly assumes the patches of the same image to be independent, leading to a loss of spatial context as information flows through the network. Incorporating contextual knowledge into predictions is particularly important given the inclination for cancerous cells to form clusters and the presence of spatial indicators for tumors. State-of-the-art methods often use attention mechanisms eventually combined with graphs to capture spatial knowledge. In this paper, we take a novel and transversal approach, addressing this issue through the lens of regularization. We propose Context-Aware Regularization for Multiple Instance Learning (CARMIL), a versatile regularization scheme designed to seamlessly integrate spatial knowledge into any MIL model. Additionally, we present a new and generic metric to quantify the Context-Awareness of any MIL model when applied to Whole Slide Images, resolving a previously unexplored gap in the field. The efficacy of our framework is evaluated for two survival analysis tasks on glioblastoma (TCGA GBM) and colon cancer data (TCGA COAD).

Muhammad Asad, Lucas Fidon, Tom Vercauteren

Automatic segmentation of lung lesions associated with COVID-19 in CT images requires large amount of annotated volumes. Annotations mandate expert knowledge and are time-intensive to obtain through fully manual segmentation methods. Additionally, lung lesions have large inter-patient variations, with some pathologies having similar visual appearance as healthy lung tissues. This poses a challenge when applying existing semi-automatic interactive segmentation techniques for data labelling. To address these challenges, we propose an efficient convolutional neural networks (CNNs) that can be learned online while the annotator provides scribble-based interaction. To accelerate learning from only the samples labelled through user-interactions, a patch-based approach is used for training the network. Moreover, we use weighted cross-entropy loss to address the class imbalance that may result from user-interactions. During online inference, the learned network is applied to the whole input volume using a fully convolutional approach. We compare our proposed method with state-of-the-art using synthetic scribbles and show that it outperforms existing methods on the task of annotating lung lesions associated with COVID-19, achieving 16% higher Dice score while reducing execution time by 3$\times$ and requiring 9000 lesser scribbles-based labelled voxels. Due to the online learning aspect, our approach adapts quickly to user input, resulting in high quality segmentation labels. Source code for ECONet is available at: https://github.com/masadcv/ECONet-MONAILabel.

Lucas Fidon, Suprosanna Shit, Ivan Ezhov et al.

Brain tumor segmentation from multiple Magnetic Resonance Imaging (MRI) modalities is a challenging task in medical image computation. The main challenges lie in the generalizability to a variety of scanners and imaging protocols. In this paper, we explore strategies to increase model robustness without increasing inference time. Towards this aim, we explore finding a robust ensemble from models trained using different losses, optimizers, and train-validation data split. Importantly, we explore the inclusion of a transformer in the bottleneck of the U-Net architecture. While we find transformer in the bottleneck performs slightly worse than the baseline U-Net in average, the generalized Wasserstein Dice loss consistently produces superior results. Further, we adopt an efficient test time augmentation strategy for faster and robust inference. Our final ensemble of seven 3D U-Nets with test-time augmentation produces an average dice score of 89.4% and an average Hausdorff 95% distance of 10.0 mm when evaluated on the BraTS 2021 testing dataset. Our code and trained models are publicly available at https://github.com/LucasFidon/TRABIT_BraTS2021.

Lucas Fidon, Michael Aertsen, Doaa Emam et al.

Deep neural networks have increased the accuracy of automatic segmentation, however, their accuracy depends on the availability of a large number of fully segmented images. Methods to train deep neural networks using images for which some, but not all, regions of interest are segmented are necessary to make better use of partially annotated datasets. In this paper, we propose the first axiomatic definition of label-set loss functions that are the loss functions that can handle partially segmented images. We prove that there is one and only one method to convert a classical loss function for fully segmented images into a proper label-set loss function. Our theory also allows us to define the leaf-Dice loss, a label-set generalization of the Dice loss particularly suited for partial supervision with only missing labels. Using the leaf-Dice loss, we set a new state of the art in partially supervised learning for fetal brain 3D MRI segmentation. We achieve a deep neural network able to segment white matter, ventricles, cerebellum, extra-ventricular CSF, cortical gray matter, deep gray matter, brainstem, and corpus callosum based on fetal brain 3D MRI of anatomically normal fetuses or with open spina bifida. Our implementation of the proposed label-set loss functions is available at https://github.com/LucasFidon/label-set-loss-functions

Marta B. M. Ranzini, Lucas Fidon, Sébastien Ourselin et al.

In fetal Magnetic Resonance Imaging, Super Resolution Reconstruction (SRR) algorithms are becoming popular tools to obtain high-resolution 3D volume reconstructions from low-resolution stacks of 2D slices, acquired at different orientations. To be effective, these algorithms often require accurate segmentation of the region of interest, such as the fetal brain in suspected pathological cases. In the case of Spina Bifida, Ebner, Wang et al. (NeuroImage, 2020) combined their SRR algorithm with a 2-step segmentation pipeline (2D localisation followed by a 2D segmentation network). However, if the localisation step fails, the second network is not able to recover a correct brain mask, thus requiring manual corrections for an effective SRR. In this work, we aim at improving the fetal brain segmentation for SRR in Spina Bifida. We hypothesise that a well-trained single-step UNet can achieve accurate performance, avoiding the need of a 2-step approach. We propose a new tool for fetal brain segmentation called MONAIfbs, which takes advantage of the Medical Open Network for Artificial Intelligence (MONAI) framework. Our network is based on the dynamic UNet (dynUNet), an adaptation of the nnU-Net framework. When compared to the original 2-step approach proposed in Ebner-Wang, and the same Ebner-Wang approach retrained with the expanded dataset available for this work, the dynUNet showed to achieve higher performance using a single step only. It also showed to reduce the number of outliers, as only 28 stacks obtained Dice score less than 0.9, compared to 68 for Ebner-Wang and 53 Ebner-Wang expanded. The proposed dynUNet model thus provides an improvement of the state-of-the-art fetal brain segmentation techniques, reducing the need for manual correction in automated SRR pipelines. Our code and our trained model are made publicly available at https://github.com/gift-surg/MONAIfbs.

Abel Díaz Berenguer, Hichem Sahli, Boris Joukovsky et al.

Our motivating application is a real-world problem: COVID-19 classification from CT imaging, for which we present an explainable Deep Learning approach based on a semi-supervised classification pipeline that employs variational autoencoders to extract efficient feature embedding. We have optimized the architecture of two different networks for CT images: (i) a novel conditional variational autoencoder (CVAE) with a specific architecture that integrates the class labels inside the encoder layers and uses side information with shared attention layers for the encoder, which make the most of the contextual clues for representation learning, and (ii) a downstream convolutional neural network for supervised classification using the encoder structure of the CVAE. With the explainable classification results, the proposed diagnosis system is very effective for COVID-19 classification. Based on the promising results obtained qualitatively and quantitatively, we envisage a wide deployment of our developed technique in large-scale clinical studies.Code is available at https://git.etrovub.be/AVSP/ct-based-covid-19-diagnostic-tool.git.

Sofie Tilborghs, Ine Dirks, Lucas Fidon et al.

Recent research on COVID-19 suggests that CT imaging provides useful information to assess disease progression and assist diagnosis, in addition to help understanding the disease. There is an increasing number of studies that propose to use deep learning to provide fast and accurate quantification of COVID-19 using chest CT scans. The main tasks of interest are the automatic segmentation of lung and lung lesions in chest CT scans of confirmed or suspected COVID-19 patients. In this study, we compare twelve deep learning algorithms using a multi-center dataset, including both open-source and in-house developed algorithms. Results show that ensembling different methods can boost the overall test set performance for lung segmentation, binary lesion segmentation and multiclass lesion segmentation, resulting in mean Dice scores of 0.982, 0.724 and 0.469, respectively. The resulting binary lesions were segmented with a mean absolute volume error of 91.3 ml. In general, the task of distinguishing different lesion types was more difficult, with a mean absolute volume difference of 152 ml and mean Dice scores of 0.369 and 0.523 for consolidation and ground glass opacity, respectively. All methods perform binary lesion segmentation with an average volume error that is better than visual assessment by human raters, suggesting these methods are mature enough for a large-scale evaluation for use in clinical practice.

Lucas Fidon, Michael Aertsen, Thomas Deprest et al.

Limiting failures of machine learning systems is of paramount importance for safety-critical applications. In order to improve the robustness of machine learning systems, Distributionally Robust Optimization (DRO) has been proposed as a generalization of Empirical Risk Minimization (ERM). However, its use in deep learning has been severely restricted due to the relative inefficiency of the optimizers available for DRO in comparison to the wide-spread variants of Stochastic Gradient Descent (SGD) optimizers for ERM. We propose SGD with hardness weighted sampling, a principled and efficient optimization method for DRO in machine learning that is particularly suited in the context of deep learning. Similar to a hard example mining strategy in practice, the proposed algorithm is straightforward to implement and computationally as efficient as SGD-based optimizers used for deep learning, requiring minimal overhead computation. In contrast to typical ad hoc hard mining approaches, we prove the convergence of our DRO algorithm for over-parameterized deep learning networks with ReLU activation and a finite number of layers and parameters. Our experiments on fetal brain 3D MRI segmentation and brain tumor segmentation in MRI demonstrate the feasibility and the usefulness of our approach. Using our hardness weighted sampling for training a state-of-the-art deep learning pipeline leads to improved robustness to anatomical variabilities in automatic fetal brain 3D MRI segmentation using deep learning and to improved robustness to the image protocol variations in brain tumor segmentation. Our code is available at https://github.com/LucasFidon/HardnessWeightedSampler.

Eli Gibson, Wenqi Li, Carole Sudre et al.

Medical image analysis and computer-assisted intervention problems are increasingly being addressed with deep-learning-based solutions. Established deep-learning platforms are flexible but do not provide specific functionality for medical image analysis and adapting them for this application requires substantial implementation effort. Thus, there has been substantial duplication of effort and incompatible infrastructure developed across many research groups. This work presents the open-source NiftyNet platform for deep learning in medical imaging. The ambition of NiftyNet is to accelerate and simplify the development of these solutions, and to provide a common mechanism for disseminating research outputs for the community to use, adapt and build upon. NiftyNet provides a modular deep-learning pipeline for a range of medical imaging applications including segmentation, regression, image generation and representation learning applications. Components of the NiftyNet pipeline including data loading, data augmentation, network architectures, loss functions and evaluation metrics are tailored to, and take advantage of, the idiosyncracies of medical image analysis and computer-assisted intervention. NiftyNet is built on TensorFlow and supports TensorBoard visualization of 2D and 3D images and computational graphs by default. We present 3 illustrative medical image analysis applications built using NiftyNet: (1) segmentation of multiple abdominal organs from computed tomography; (2) image regression to predict computed tomography attenuation maps from brain magnetic resonance images; and (3) generation of simulated ultrasound images for specified anatomical poses. NiftyNet enables researchers to rapidly develop and distribute deep learning solutions for segmentation, regression, image generation and representation learning applications, or extend the platform to new applications.

Lucas Fidon

Despite the recent success of deep learning methods at achieving new state-of-the-art accuracy for medical image segmentation, some major limitations are still restricting their deployment into clinics. One major limitation of deep learning-based segmentation methods is their lack of robustness to variability in the image acquisition protocol and in the imaged anatomy that were not represented or were underrepresented in the training dataset. This suggests adding new manually segmented images to the training dataset to better cover the image variability. However, in most cases, the manual segmentation of medical images requires highly skilled raters and is time-consuming, making this solution prohibitively expensive. Even when manually segmented images from different sources are available, they are rarely annotated for exactly the same regions of interest. This poses an additional challenge for current state-of-the-art deep learning segmentation methods that rely on supervised learning and therefore require all the regions of interest to be segmented for all the images to be used for training. This thesis introduces new mathematical and optimization methods to mitigate those limitations.

Lucas Fidon, Michael Aertsen, Suprosanna Shit et al.

This paper describes our method for our participation in the FeTA challenge2021 (team name: TRABIT). The performance of convolutional neural networks for medical image segmentation is thought to correlate positively with the number of training data. The FeTA challenge does not restrict participants to using only the provided training data but also allows for using other publicly available sources. Yet, open access fetal brain data remains limited. An advantageous strategy could thus be to expand the training data to cover broader perinatal brain imaging sources. Perinatal brain MRIs, other than the FeTA challenge data, that are currently publicly available, span normal and pathological fetal atlases as well as neonatal scans. However, perinatal brain MRIs segmented in different datasets typically come with different annotation protocols. This makes it challenging to combine those datasets to train a deep neural network. We recently proposed a family of loss functions, the label-set loss functions, for partially supervised learning. Label-set loss functions allow to train deep neural networks with partially segmented images, i.e. segmentations in which some classes may be grouped into super-classes. We propose to use label-set loss functions to improve the segmentation performance of a state-of-the-art deep learning pipeline for multi-class fetal brain segmentation by merging several publicly available datasets. To promote generalisability, our approach does not introduce any additional hyper-parameters tuning.

Lucas Fidon, Michael Aertsen, Nada Mufti et al.

The performance of deep neural networks typically increases with the number of training images. However, not all images have the same importance towards improved performance and robustness. In fetal brain MRI, abnormalities exacerbate the variability of the developing brain anatomy compared to non-pathological cases. A small number of abnormal cases, as is typically available in clinical datasets used for training, are unlikely to fairly represent the rich variability of abnormal developing brains. This leads machine learning systems trained by maximizing the average performance to be biased toward non-pathological cases. This problem was recently referred to as hidden stratification. To be suited for clinical use, automatic segmentation methods need to reliably achieve high-quality segmentation outcomes also for pathological cases. In this paper, we show that the state-of-the-art deep learning pipeline nnU-Net has difficulties to generalize to unseen abnormal cases. To mitigate this problem, we propose to train a deep neural network to minimize a percentile of the distribution of per-volume loss over the dataset. We show that this can be achieved by using Distributionally Robust Optimization (DRO). DRO automatically reweights the training samples with lower performance, encouraging nnU-Net to perform more consistently on all cases. We validated our approach using a dataset of 368 fetal brain T2w MRIs, including 124 MRIs of open spina bifida cases and 51 MRIs of cases with other severe abnormalities of brain development.

Lucas Fidon, Sebastien Ourselin, Tom Vercauteren

Training a deep neural network is an optimization problem with four main ingredients: the design of the deep neural network, the per-sample loss function, the population loss function, and the optimizer. However, methods developed to compete in recent BraTS challenges tend to focus only on the design of deep neural network architectures, while paying less attention to the three other aspects. In this paper, we experimented with adopting the opposite approach. We stuck to a generic and state-of-the-art 3D U-Net architecture and experimented with a non-standard per-sample loss function, the generalized Wasserstein Dice loss, a non-standard population loss function, corresponding to distributionally robust optimization, and a non-standard optimizer, Ranger. Those variations were selected specifically for the problem of multi-class brain tumor segmentation. The generalized Wasserstein Dice loss is a per-sample loss function that allows taking advantage of the hierarchical structure of the tumor regions labeled in BraTS. Distributionally robust optimization is a generalization of empirical risk minimization that accounts for the presence of underrepresented subdomains in the training dataset. Ranger is a generalization of the widely used Adam optimizer that is more stable with small batch size and noisy labels. We found that each of those variations of the optimization of deep neural networks for brain tumor segmentation leads to improvements in terms of Dice scores and Hausdorff distances. With an ensemble of three deep neural networks trained with various optimization procedures, we achieved promising results on the validation dataset of the BraTS 2020 challenge. Our ensemble ranked fourth out of the 693 registered teams for the segmentation task of the BraTS 2020 challenge.

Wenqi Li, Guotai Wang, Lucas Fidon et al.

Deep convolutional neural networks are powerful tools for learning visual representations from images. However, designing efficient deep architectures to analyse volumetric medical images remains challenging. This work investigates efficient and flexible elements of modern convolutional networks such as dilated convolution and residual connection. With these essential building blocks, we propose a high-resolution, compact convolutional network for volumetric image segmentation. To illustrate its efficiency of learning 3D representation from large-scale image data, the proposed network is validated with the challenging task of parcellating 155 neuroanatomical structures from brain MR images. Our experiments show that the proposed network architecture compares favourably with state-of-the-art volumetric segmentation networks while being an order of magnitude more compact. We consider the brain parcellation task as a pretext task for volumetric image segmentation; our trained network potentially provides a good starting point for transfer learning. Additionally, we show the feasibility of voxel-level uncertainty estimation using a sampling approximation through dropout.

Lucas Fidon, Wenqi Li, Luis C. Garcia-Peraza-Herrera et al.

The Dice score is widely used for binary segmentation due to its robustness to class imbalance. Soft generalisations of the Dice score allow it to be used as a loss function for training convolutional neural networks (CNN). Although CNNs trained using mean-class Dice score achieve state-of-the-art results on multi-class segmentation, this loss function does neither take advantage of inter-class relationships nor multi-scale information. We argue that an improved loss function should balance misclassifications to favour predictions that are semantically meaningful. This paper investigates these issues in the context of multi-class brain tumour segmentation. Our contribution is threefold. 1) We propose a semantically-informed generalisation of the Dice score for multi-class segmentation based on the Wasserstein distance on the probabilistic label space. 2) We propose a holistic CNN that embeds spatial information at multiple scales with deep supervision. 3) We show that the joint use of holistic CNNs and generalised Wasserstein Dice scores achieves segmentations that are more semantically meaningful for brain tumour segmentation.

Lucas Fidon, Wenqi Li, Luis C. Garcia-Peraza-Herrera et al.

Brain tumour segmentation plays a key role in computer-assisted surgery. Deep neural networks have increased the accuracy of automatic segmentation significantly, however these models tend to generalise poorly to different imaging modalities than those for which they have been designed, thereby limiting their applications. For example, a network architecture initially designed for brain parcellation of monomodal T1 MRI can not be easily translated into an efficient tumour segmentation network that jointly utilises T1, T1c, Flair and T2 MRI. To tackle this, we propose a novel scalable multimodal deep learning architecture using new nested structures that explicitly leverage deep features within or across modalities. This aims at making the early layers of the architecture structured and sparse so that the final architecture becomes scalable to the number of modalities. We evaluate the scalable architecture for brain tumour segmentation and give evidence of its regularisation effect compared to the conventional concatenation approach.