The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Deep convolutional neural networks (CNN) have proven to be remarkably effective in semantic segmentation tasks. Most popular loss functions were introduced targeting improved volumetric scores, such as the Dice coefficient (DSC). By design, DSC can tackle class imbalance, however, it does not recognize instance imbalance within a class. As a result, a large foreground instance can dominate minor instances and still produce a satisfactory DSC. Nevertheless, detecting tiny instances is crucial for many applications, such as disease monitoring. For example, it is imperative to locate and surveil small-scale lesions in the follow-up of multiple sclerosis patients. We propose a novel family of loss functions, \emph{blob loss}, primarily aimed at maximizing instance-level detection metrics, such as F1 score and sensitivity. \emph{Blob loss} is designed for semantic segmentation problems where detecting multiple instances matters. We extensively evaluate a DSC-based \emph{blob loss} in five complex 3D semantic segmentation tasks featuring pronounced instance heterogeneity in terms of texture and morphology. Compared to soft Dice loss, we achieve 5% improvement for MS lesions, 3% improvement for liver tumor, and an average 2% improvement for microscopy segmentation tasks considering F1 score.

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.

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.

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.

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.

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.

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.

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.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e. 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that undergone gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.