Evangelia Christodoulou

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.

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.

Patrick Godau, Piotr Kalinowski, Evangelia Christodoulou et al.

Domain gaps are among the most relevant roadblocks in the clinical translation of machine learning (ML)-based solutions for medical image analysis. While current research focuses on new training paradigms and network architectures, little attention is given to the specific effect of prevalence shifts on an algorithm deployed in practice. Such discrepancies between class frequencies in the data used for a method's development/validation and that in its deployment environment(s) are of great importance, for example in the context of artificial intelligence (AI) democratization, as disease prevalences may vary widely across time and location. Our contribution is twofold. First, we empirically demonstrate the potentially severe consequences of missing prevalence handling by analyzing (i) the extent of miscalibration, (ii) the deviation of the decision threshold from the optimum, and (iii) the ability of validation metrics to reflect neural network performance on the deployment population as a function of the discrepancy between development and deployment prevalence. Second, we propose a workflow for prevalence-aware image classification that uses estimated deployment prevalences to adjust a trained classifier to a new environment, without requiring additional annotated deployment data. Comprehensive experiments based on a diverse set of 30 medical classification tasks showcase the benefit of the proposed workflow in generating better classifier decisions and more reliable performance estimates compared to current practice.

Thuy Nuong Tran, Tim Adler, Amine Yamlahi et al.

Validation metrics are a key prerequisite for the reliable tracking of scientific progress and for deciding on the potential clinical translation of methods. While recent initiatives aim to develop comprehensive theoretical frameworks for understanding metric-related pitfalls in image analysis problems, there is a lack of experimental evidence on the concrete effects of common and rare pitfalls on specific applications. We address this gap in the literature in the context of colon cancer screening. Our contribution is twofold. Firstly, we present the winning solution of the Endoscopy computer vision challenge (EndoCV) on colon cancer detection, conducted in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2022. Secondly, we demonstrate the sensitivity of commonly used metrics to a range of hyperparameters as well as the consequences of poor metric choices. Based on comprehensive validation studies performed with patient data from six clinical centers, we found all commonly applied object detection metrics to be subject to high inter-center variability. Furthermore, our results clearly demonstrate that the adaptation of standard hyperparameters used in the computer vision community does not generally lead to the clinically most plausible results. Finally, we present localization criteria that correspond well to clinical relevance. Our work could be a first step towards reconsidering common validation strategies in automatic colon cancer screening applications.

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.

Annika Reinke, Evangelia Christodoulou, Sthuthi Sadananda et al.

Benchmarking competitions are central to the development of artificial intelligence (AI) in medical imaging, defining performance standards and shaping methodological progress. However, it remains unclear whether these benchmarks provide data that are sufficiently representative, accessible, and reusable to support clinically meaningful AI. In this work, we assess fairness along two complementary dimensions: (1) whether challenge datasets are representative of real-world clinical diversity, and (2) whether they are accessible and legally reusable in line with the FAIR principles. To address this question, we conducted a large-scale systematic study of 241 biomedical image analysis challenges comprising 458 tasks across 19 imaging modalities. Our findings show substantial biases in dataset composition, including geographic location, modality-, and problem type-related biases, indicating that current benchmarks do not adequately reflect real-world clinical diversity. Despite their widespread influence, challenge datasets were frequently constrained by restrictive or ambiguous access conditions, inconsistent or non-compliant licensing practices, and incomplete documentation, limiting reproducibility and long-term reuse. Together, these shortcomings expose foundational fairness limitations in our benchmarking ecosystem and highlight a disconnect between leaderboard success and clinical relevance.

Leon Mayer, Piotr Kalinowski, Caroline Ebersbach et al.

Vision-language models are increasingly integrated into clinical workflows. However, existing benchmarks primarily assess performance on common anatomical presentations and fail to capture the challenges posed by rare variants. To address this gap, we introduce AdversarialAnatomyBench, the first benchmark comprising naturally occurring rare anatomical variants across diverse imaging modalities and anatomical regions. We call such variants that violate learned priors about "typical" human anatomy natural adversarial anatomy. Benchmarking 22 state-of-the-art VLMs with AdversarialAnatomyBench yielded three key insights. First, when queried with basic medical perception tasks, mean accuracy dropped from 74% on typical to 29% on atypical anatomy. Even the best-performing models, GPT-5, Gemini 2.5 Pro, and Llama 4 Maverick, showed performance drops of 41-51%. Second, model errors closely mirrored expected anatomical biases. Third, neither model scaling nor interventions, including bias-aware prompting and test-time reasoning, resolved these issues. These findings highlight a critical and previously unquantified limitation in current VLM: their poor generalization to rare anatomical presentations. AdversarialAnatomyBench provides a foundation for systematically measuring and mitigating anatomical bias in multimodal medical AI systems.

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.

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.