Analyzing the Quality and Challenges of Uncertainty Estimations for Brain Tumor Segmentation

Automatic segmentation of brain tumors has the potential to enable volumetric measures and high-throughput analysis in the clinical setting. Reaching this potential seems almost achieved, considering the steady increase in segmentation accuracy. However, despite segmentation accuracy, the current methods still do not meet the robustness levels required for patient-centered clinical use. In this regard, uncertainty estimates are a promising direction to improve the robustness of automated segmentation systems. Different uncertainty estimation methods have been proposed, but little is known about their usefulness and limitations for brain tumor segmentation. In this study, we present an analysis of the most commonly used uncertainty estimation methods in regards to benefits and challenges for brain tumor segmentation. We evaluated their quality in terms of calibration, segmentation error localization, and segmentation failure detection. Our results show that the uncertainty methods are typically well-calibrated when evaluated at the dataset level. Evaluated at the subject level, we found notable miscalibrations and limited segmentation error localization (e.g., for correcting segmentations), which hinder the direct use of the voxel-wise uncertainties. Nevertheless, voxel-wise uncertainty showed value to detect failed segmentations when uncertainty estimates are aggregated at the subject level. Therefore, we suggest a careful usage of voxel-wise uncertainty measures and highlight the importance of developing solutions that address the subject-level requirements on calibration and segmentation error localization

On the Effect of Inter-observer Variability for a Reliable Estimation of Uncertainty of Medical Image Segmentation

Uncertainty estimation methods are expected to improve the understanding and quality of computer-assisted methods used in medical applications (e.g., neurosurgical interventions, radiotherapy planning), where automated medical image segmentation is crucial. In supervised machine learning, a common practice to generate ground truth label data is to merge observer annotations. However, as many medical image tasks show a high inter-observer variability resulting from factors such as image quality, different levels of user expertise and domain knowledge, little is known as to how inter-observer variability and commonly used fusion methods affect the estimation of uncertainty of automated image segmentation. In this paper we analyze the effect of common image label fusion techniques on uncertainty estimation, and propose to learn the uncertainty among observers. The results highlight the negative effect of fusion methods applied in deep learning, to obtain reliable estimates of segmentation uncertainty. Additionally, we show that the learned observers' uncertainty can be combined with current standard Monte Carlo dropout Bayesian neural networks to characterize uncertainty of model's parameters.Comment: Appears in Medical Image Computing and Computer Assisted Interventions (MICCAI), 201

pymia: A Python package for data handling and evaluation in deep learning-based medical image analysis

Background and Objective: Deep learning enables tremendous progress in medical image analysis. One driving force of this progress are open-source frameworks like TensorFlow and PyTorch. However, these frameworks rarely address issues specific to the domain of medical image analysis, such as 3-D data handling and distance metrics for evaluation. pymia, an open-source Python package, tries to address these issues by providing flexible data handling and evaluation independent of the deep learning framework. Methods: The pymia package provides data handling and evaluation functionalities. The data handling allows flexible medical image handling in every commonly used format (e.g., 2-D, 2.5-D, and 3-D; full- or patch-wise). Even data beyond images like demographics or clinical reports can easily be integrated into deep learning pipelines. The evaluation allows stand-alone result calculation and reporting, as well as performance monitoring during training using a vast amount of domain-specific metrics for segmentation, reconstruction, and regression. Results: The pymia package is highly flexible, allows for fast prototyping, and reduces the burden of implementing data handling routines and evaluation methods. While data handling and evaluation are independent of the deep learning framework used, they can easily be integrated into TensorFlow and PyTorch pipelines. The developed package was successfully used in a variety of research projects for segmentation, reconstruction, and regression. Conclusions: The pymia package fills the gap of current deep learning frameworks regarding data handling and evaluation in medical image analysis. It is available at https://github.com/rundherum/pymia and can directly be installed from the Python Package Index using pip install pymia.Comment: first and last author contributed equall

Uncertainty-driven Sanity Check: Application to Postoperative Brain Tumor Cavity Segmentation

Uncertainty estimates of modern neuronal networks provide additional information next to the computed predictions and are thus expected to improve the understanding of the underlying model. Reliable uncertainties are particularly interesting for safety-critical computer-assisted applications in medicine, e.g., neurosurgical interventions and radiotherapy planning. We propose an uncertainty-driven sanity check for the identification of segmentation results that need particular expert review. Our method uses a fully-convolutional neural network and computes uncertainty estimates by the principle of Monte Carlo dropout. We evaluate the performance of the proposed method on a clinical dataset with 30 postoperative brain tumor images. The method can segment the highly inhomogeneous resection cavities accurately (Dice coefficients 0.792 $\pm$ 0.154). Furthermore, the proposed sanity check is able to detect the worst segmentation and three out of the four outliers. The results highlight the potential of using the additional information from the model's parameter uncertainty to validate the segmentation performance of a deep learning model.Comment: Appears in Medical Imaging with Deep Learning (MIDL), 201

Learning Bloch Simulations for MR Fingerprinting by Invertible Neural Networks

Magnetic resonance fingerprinting (MRF) enables fast and multiparametric MR imaging. Despite fast acquisition, the state-of-the-art reconstruction of MRF based on dictionary matching is slow and lacks scalability. To overcome these limitations, neural network (NN) approaches estimating MR parameters from fingerprints have been proposed recently. Here, we revisit NN-based MRF reconstruction to jointly learn the forward process from MR parameters to fingerprints and the backward process from fingerprints to MR parameters by leveraging invertible neural networks (INNs). As a proof-of-concept, we perform various experiments showing the benefit of learning the forward process, i.e., the Bloch simulations, for improved MR parameter estimation. The benefit especially accentuates when MR parameter estimation is difficult due to MR physical restrictions. Therefore, INNs might be a feasible alternative to the current solely backward-based NNs for MRF reconstruction.Comment: Accepted at MICCAI MLMIR 202

Unsupervised out-of-distribution detection for safer robotically-guided retinal microsurgery

Purpose: A fundamental problem in designing safe machine learning systems is identifying when samples presented to a deployed model differ from those observed at training time. Detecting so-called out-of-distribution (OoD) samples is crucial in safety-critical applications such as robotically-guided retinal microsurgery, where distances between the instrument and the retina are derived from sequences of 1D images that are acquired by an instrument-integrated optical coherence tomography (iiOCT) probe. Methods: This work investigates the feasibility of using an OoD detector to identify when images from the iiOCT probe are inappropriate for subsequent machine learning-based distance estimation. We show how a simple OoD detector based on the Mahalanobis distance can successfully reject corrupted samples coming from real-world ex-vivo porcine eyes. Results: Our results demonstrate that the proposed approach can successfully detect OoD samples and help maintain the performance of the downstream task within reasonable levels. MahaAD outperformed a supervised approach trained on the same kind of corruptions and achieved the best performance in detecting OoD cases from a collection of iiOCT samples with real-world corruptions. Conclusion: The results indicate that detecting corrupted iiOCT data through OoD detection is feasible and does not need prior knowledge of possible corruptions. Consequently, MahaAD could aid in ensuring patient safety during robotically-guided microsurgery by preventing deployed prediction models from estimating distances that put the patient at risk.Comment: Accepted at IPCAI 202

Tournesol: Permissionless Collaborative Algorithmic Governance with Security Guarantees

Recommendation algorithms play an increasingly central role in our societies. However, thus far, these algorithms are mostly designed and parameterized unilaterally by private groups or governmental authorities. In this paper, we present an end-to-end permissionless collaborative algorithmic governance method with security guarantees. Our proposed method is deployed as part of an open-source content recommendation platform https://tournesol.app, whose recommender is collaboratively parameterized by a community of (non-technical) contributors. This algorithmic governance is achieved through three main steps. First, the platform contains a mechanism to assign voting rights to the contributors. Second, the platform uses a comparison-based model to evaluate the individual preferences of contributors. Third, the platform aggregates the judgements of all contributors into collective scores for content recommendations. We stress that the first and third steps are vulnerable to attacks from malicious contributors. To guarantee the resilience against fake accounts, the first step combines email authentication, a vouching mechanism, a novel variant of the reputation-based EigenTrust algorithm and an adaptive voting rights assignment for alternatives that are scored by too many untrusted accounts. To provide resilience against malicious authenticated contributors, we adapt Mehestan, an algorithm previously proposed for robust sparse voting. We believe that these algorithms provide an appealing foundation for a collaborative, effective, scalable, fair, contributor-friendly, interpretable and secure governance. We conclude by highlighting key challenges to make our solution applicable to larger-scale settings.Comment: 31 pages, 5 figure

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article