Michela Antonelli

Lena Maier-Hein, Annika Reinke, Patrick Godau et al. · utoronto

Increasing evidence shows that flaws in machine learning (ML) algorithm validation are an underestimated global problem. Particularly in automatic biomedical image analysis, chosen performance metrics often do not reflect the domain interest, thus failing to adequately measure scientific progress and hindering translation of ML techniques into practice. To overcome this, our large international expert consortium created Metrics Reloaded, a comprehensive framework guiding researchers in the problem-aware selection of metrics. Following the convergence of ML methodology across application domains, Metrics Reloaded fosters the convergence of validation methodology. The framework was developed in a multi-stage Delphi process and is based on the novel concept of a problem fingerprint - a structured representation of the given problem that captures all aspects that are relevant for metric selection, from the domain interest to the properties of the target structure(s), data set and algorithm output. Based on the problem fingerprint, users are guided through the process of choosing and applying appropriate validation metrics while being made aware of potential pitfalls. Metrics Reloaded targets image analysis problems that can be interpreted as a classification task at image, object or pixel level, namely image-level classification, object detection, semantic segmentation, and instance segmentation tasks. To improve the user experience, we implemented the framework in the Metrics Reloaded online tool, which also provides a point of access to explore weaknesses, strengths and specific recommendations for the most common validation metrics. The broad applicability of our framework across domains is demonstrated by an instantiation for various biological and medical image analysis use cases.

Annika Reinke, Minu D. Tizabi, Michael Baumgartner et al.

Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation.

Akshit Achara, Yovin Yathathugoda, Nick Byrne et al.

The robustness of machine learning models can be compromised by spurious correlations between non-causal features in the input data and target labels. A common way to test for such correlations is to train on data where the label is strongly tied to some non-causal cue, then evaluate on examples where that tie no longer holds. This idea is well established for classification tasks, but for semantic segmentation the specific failure modes are not well understood. We show that a model may achieve reasonable overlap while assigning the wrong semantic label, swapping one plausible foreground class for another, even when object boundaries are largely correct. We focus on this semantic label-flip behaviour and quantify it with a simple diagnostic (Flip) that counts how often ground truth foreground pixels are assigned the wrong foreground identity while remaining predicted as foreground. In a setting where category and scene are correlated during training, increasing the correlation consistently widens the gap between common and rare test conditions and increases these within-object label swaps on counterfactual groups. Overall, our results motivate assessing segmentation robustness under distribution shift beyond overlap by decomposing foreground errors into correct pixels, flipped-identity pixels, and missed-to-background pixels. We also propose an entropy-based, ground truth label-free `flip-risk' score, which is computed from foreground identity uncertainty, and show that it can flag flip-prone cases at inference time. Code is available at https://github.com/acharaakshit/label-flips.

Evangelia Christodoulou, Annika Reinke, Rola Houhou et al.

Medical imaging is spearheading the AI transformation of healthcare. Performance reporting is key to determine which methods should be translated into clinical practice. Frequently, broad conclusions are simply derived from mean performance values. In this paper, we argue that this common practice is often a misleading simplification as it ignores performance variability. Our contribution is threefold. (1) Analyzing all MICCAI segmentation papers (n = 221) published in 2023, we first observe that more than 50% of papers do not assess performance variability at all. Moreover, only one (0.5%) paper reported confidence intervals (CIs) for model performance. (2) To address the reporting bottleneck, we show that the unreported standard deviation (SD) in segmentation papers can be approximated by a second-order polynomial function of the mean Dice similarity coefficient (DSC). Based on external validation data from 56 previous MICCAI challenges, we demonstrate that this approximation can accurately reconstruct the CI of a method using information provided in publications. (3) Finally, we reconstructed 95% CIs around the mean DSC of MICCAI 2023 segmentation papers. The median CI width was 0.03 which is three times larger than the median performance gap between the first and second ranked method. For more than 60% of papers, the mean performance of the second-ranked method was within the CI of the first-ranked method. We conclude that current publications typically do not provide sufficient evidence to support which models could potentially be translated into clinical practice.

Lucia Innocenti, Michela Antonelli, Francesco Cremonesi et al.

Healthcare data is often split into medium/small-sized collections across multiple hospitals and access to it is encumbered by privacy regulations. This brings difficulties to use them for the development of machine learning and deep learning models, which are known to be data-hungry. One way to overcome this limitation is to use collaborative learning (CL) methods, which allow hospitals to work collaboratively to solve a task, without the need to explicitly share local data. In this paper, we address a prostate segmentation problem from MRI in a collaborative scenario by comparing two different approaches: federated learning (FL) and consensus-based methods (CBM). To the best of our knowledge, this is the first work in which CBM, such as label fusion techniques, are used to solve a problem of collaborative learning. In this setting, CBM combine predictions from locally trained models to obtain a federated strong learner with ideally improved robustness and predictive variance properties. Our experiments show that, in the considered practical scenario, CBMs provide equal or better results than FL, while being highly cost-effective. Our results demonstrate that the consensus paradigm may represent a valid alternative to FL for typical training tasks in medical imaging.

Pascaline André, Charles Heitz, Evangelia Christodoulou et al.

Performance uncertainty quantification is essential for reliable validation and eventual clinical translation of medical imaging artificial intelligence (AI). Confidence intervals (CIs) play a central role in this process by indicating how precise a reported performance estimate is. Yet, due to the limited amount of work examining CI behavior in medical imaging, the community remains largely unaware of how many diverse CI methods exist and how they behave in specific settings. The purpose of this study is to close this gap. To this end, we conducted a large-scale empirical analysis across a total of 24 segmentation and classification tasks, using 19 trained models per task group, a broad spectrum of commonly used performance metrics, multiple aggregation strategies, and several widely adopted CI methods. Reliability (coverage) and precision (width) of each CI method were estimated across all settings to characterize their dependence on study characteristics. Our analysis revealed five principal findings: 1) the sample size required for reliable CIs varies from a few dozens to several thousands of cases depending on study parameters; 2) CI behavior is strongly affected by the choice of performance metric; 3) aggregation strategy substantially influences the reliability of CIs, e.g. they require more observations for macro than for micro; 4) the machine learning problem (segmentation versus classification) modulates these effects; 5) different CI methods are not equally reliable and precise depending on the use case. These results form key components for the development of future guidelines on reporting performance uncertainty in medical imaging AI.

Andres Diaz-Pinto, Pritesh Mehta, Sachidanand Alle et al.

Automatic segmentation of medical images is a key step for diagnostic and interventional tasks. However, achieving this requires large amounts of annotated volumes, which can be tedious and time-consuming task for expert annotators. In this paper, we introduce DeepEdit, a deep learning-based method for volumetric medical image annotation, that allows automatic and semi-automatic segmentation, and click-based refinement. DeepEdit combines the power of two methods: a non-interactive (i.e. automatic segmentation using nnU-Net, UNET or UNETR) and an interactive segmentation method (i.e. DeepGrow), into a single deep learning model. It allows easy integration of uncertainty-based ranking strategies (i.e. aleatoric and epistemic uncertainty computation) and active learning. We propose and implement a method for training DeepEdit by using standard training combined with user interaction simulation. Once trained, DeepEdit allows clinicians to quickly segment their datasets by using the algorithm in auto segmentation mode or by providing clicks via a user interface (i.e. 3D Slicer, OHIF). We show the value of DeepEdit through evaluation on the PROSTATEx dataset for prostate/prostatic lesions and the Multi-Atlas Labeling Beyond the Cranial Vault (BTCV) dataset for abdominal CT segmentation, using state-of-the-art network architectures as baseline for comparison. DeepEdit could reduce the time and effort annotating 3D medical images compared to DeepGrow alone. Source code is available at https://github.com/Project-MONAI/MONAILabel

Benjamin Murray, Eric Kerfoot, Mark S. Graham et al.

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. Over 4.7 million participants and 189 million unique assessments have been logged since its introduction in March 2020. The success of the Covid Symptom Study creates technical challenges around effective data curation for two reasons. Firstly, the scale of the dataset means that it can no longer be easily processed using standard software on commodity hardware. Secondly, the size of the research group means that replicability and consistency of key analytics used across multiple publications becomes an issue. We present ExeTera, an open source data curation software designed to address scalability challenges and to enable reproducible research across an international research group for datasets such as the Covid Symptom Study dataset.

Amber L. Simpson, Michela Antonelli, Spyridon Bakas et al.

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.

Evangelia Christodoulou, Annika Reinke, Pascaline Andrè et al.

Performance comparisons are fundamental in medical imaging Artificial Intelligence (AI) research, often driving claims of superiority based on relative improvements in common performance metrics. However, such claims frequently rely solely on empirical mean performance. In this paper, we investigate whether newly proposed methods genuinely outperform the state of the art by analyzing a representative cohort of medical imaging papers. We quantify the probability of false claims based on a Bayesian approach that leverages reported results alongside empirically estimated model congruence to estimate whether the relative ranking of methods is likely to have occurred by chance. According to our results, the majority (>80%) of papers claims outperformance when introducing a new method. Our analysis further revealed a high probability (>5%) of false outperformance claims in 86% of classification papers and 53% of segmentation papers. These findings highlight a critical flaw in current benchmarking practices: claims of outperformance in medical imaging AI are frequently unsubstantiated, posing a risk of misdirecting future research efforts.

Yovin Yahathugoda, Davide Prezzi, Piyalitt Ittichaiwong et al.

Active Surveillance (AS) is a treatment option for managing low and intermediate-risk prostate cancer (PCa), aiming to avoid overtreatment while monitoring disease progression through serial MRI and clinical follow-up. Accurate prostate segmentation is an important preliminary step for automating this process, enabling automated detection and diagnosis of PCa. However, existing deep-learning segmentation models are often trained on single-time-point and expertly annotated datasets, making them unsuitable for longitudinal AS analysis, where multiple time points and a scarcity of expert labels hinder their effective fine-tuning. To address these challenges, we propose MambaX-Net, a novel semi-supervised, dual-scan 3D segmentation architecture that computes the segmentation for time point t by leveraging the MRI and the corresponding segmentation mask from the previous time point. We introduce two new components: (i) a Mamba-enhanced Cross-Attention Module, which integrates the Mamba block into cross attention to efficiently capture temporal evolution and long-range spatial dependencies, and (ii) a Shape Extractor Module that encodes the previous segmentation mask into a latent anatomical representation for refined zone delination. Moreover, we introduce a semi-supervised self-training strategy that leverages pseudo-labels generated from a pre-trained nnU-Net, enabling effective learning without expert annotations. MambaX-Net was evaluated on a longitudinal AS dataset, and results showed that it significantly outperforms state-of-the-art U-Net and Transformer-based models, achieving superior prostate zone segmentation even when trained on limited and noisy data.

Ashay Patel, Michela Antonelli, Sebastien Ourselin et al.

Deep learning has significantly advanced medical imaging analysis, yet variations in image resolution remain an overlooked challenge. Most methods address this by resampling images, leading to either information loss or computational inefficiencies. While solutions exist for specific tasks, no unified approach has been proposed. We introduce a resolution-invariant autoencoder that adapts spatial resizing at each layer in the network via a learned variable resizing process, replacing fixed spatial down/upsampling at the traditional factor of 2. This ensures a consistent latent space resolution, regardless of input or output resolution. Our model enables various downstream tasks to be performed on an image latent whilst maintaining performance across different resolutions, overcoming the shortfalls of traditional methods. We demonstrate its effectiveness in uncertainty-aware super-resolution, classification, and generative modelling tasks and show how our method outperforms conventional baselines with minimal performance loss across resolutions.

Francesco Cremonesi, Lucia Innocenti, Sebastien Ourselin et al.

Background. Federated learning (FL) has gained wide popularity as a collaborative learning paradigm enabling collaborative AI in sensitive healthcare applications. Nevertheless, the practical implementation of FL presents technical and organizational challenges, as it generally requires complex communication infrastructures. In this context, consensus-based learning (CBL) may represent a promising collaborative learning alternative, thanks to the ability of combining local knowledge into a federated decision system, while potentially reducing deployment overhead. Methods. In this work we propose an extensive benchmark of the accuracy and cost-effectiveness of a panel of FL and CBL methods in a wide range of collaborative medical data analysis scenarios. The benchmark includes 7 different medical datasets, encompassing 3 machine learning tasks, 8 different data modalities, and multi-centric settings involving 3 to 23 clients. Findings. Our results reveal that CBL is a cost-effective alternative to FL. When compared across the panel of medical dataset in the considered benchmark, CBL methods provide equivalent accuracy to the one achieved by FL.Nonetheless, CBL significantly reduces training time and communication cost (resp. 15 fold and 60 fold decrease) (p < 0.05). Interpretation. This study opens a novel perspective on the deployment of collaborative AI in real-world applications, whereas the adoption of cost-effective methods is instrumental to achieve sustainability and democratisation of AI by alleviating the need for extensive computational resources.

Michela Antonelli, Annika Reinke, Spyridon Bakas et al.

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts.

Annika Reinke, Minu D. Tizabi, Carole H. Sudre et al.

While the importance of automatic image analysis is continuously increasing, recent meta-research revealed major flaws with respect to algorithm validation. Performance metrics are particularly key for meaningful, objective, and transparent performance assessment and validation of the used automatic algorithms, but relatively little attention has been given to the practical pitfalls when using specific metrics for a given image analysis task. These are typically related to (1) the disregard of inherent metric properties, such as the behaviour in the presence of class imbalance or small target structures, (2) the disregard of inherent data set properties, such as the non-independence of the test cases, and (3) the disregard of the actual biomedical domain interest that the metrics should reflect. This living dynamically document has the purpose to illustrate important limitations of performance metrics commonly applied in the field of image analysis. In this context, it focuses on biomedical image analysis problems that can be phrased as image-level classification, semantic segmentation, instance segmentation, or object detection task. The current version is based on a Delphi process on metrics conducted by an international consortium of image analysis experts from more than 60 institutions worldwide.

Patrick Bilic, Patrick Christ, Hongwei Bran Li et al.

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in \url{http://medicaldecathlon.com/}. In addition, both data and online evaluation are accessible via \url{www.lits-challenge.com}.