arXiv subjects

Manuel Wiesenfarth

Publications and source records attributed to Manuel Wiesenfarth.

15 recordsLinked to original sources

arXiv2026

Principled type I error rate inflation in two-arm clinical trial designs with external control information borrowing

External information borrowing is often considered in order to improve a clinical trial's efficiency. The Bayesian approach borrows such external information by specifying an informative prior distribution. A potential issue with this procedure is that external and current information may conflict, but such inconsistency may not be predictable a priori. Robust prior choices are typically proposed to limit extreme worsening of operating characteristics (OCs) in these situations. However, trade-offs are still present and in general strict control of type I error (TIE) rate prevents any power gains. In this context, principled justifications for TIE rate inflation can be of interest. We investigate two-arm trials, with a focus on external/historical control information borrowing. We illustrate OCs trade-offs and propose an interpretable approach for external information borrowing. The approach analytically links observed prior-data conflict with allowances for TIE rate inflation and power loss. The approach does not rely on a robust prior specification, but can instead be interpreted as an adaptive choice of Bayes - or, equivalently, frequentist - test decision thresholds under the available informative prior. In addition, it can be used to evaluate any dynamic borrowing approach from a frequentist testing standpoint, and to guarantee robustness with respect to misspecification of the data generating process (i.e., design prior) in Bayesian evaluations. A development for both Normal and binomial outcomes is provided.

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arXiv2025

Information borrowing in Bayesian clinical trials: choice of tuning parameters for the robust mixture prior

External data borrowing in clinical trial designs has increased in recent years. This is accomplished in the Bayesian framework by specifying informative prior distributions. To mitigate the impact of potential inconsistency (bias) between external and current data, robust approaches have been proposed. One such approach is the robust mixture prior arising as a mixture of an informative prior and a more dispersed prior inducing dynamic borrowing. This prior requires the choice of four quantities: the mixture weight, mean, dispersion and parametric form of the robust component. To address the challenge associated with choosing these quantities, we perform a case-by-case study of their impact on specific operating characteristics in one-arm and hybrid-control trials with a normal endpoint. All four quantities were found to strongly impact the operating characteristics. As already known, variance of the robust component is linked to robustness. Less known, however, is that its location can have severe impact on test and estimation error. Further, the impact of the weight choice is strongly linked with the robust component's location and variance. We provide recommendations for the choice of the robust component parameters, prior weight, alternative functional form for this component and considerations for evaluating operating characteristics.

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arXiv2025

Xeno-learning: knowledge transfer across species in deep learning-based spectral image analysis

Novel optical imaging techniques, such as hyperspectral imaging (HSI) combined with machine learning-based (ML) analysis, have the potential to revolutionize clinical surgical imaging. However, these novel modalities face a shortage of large-scale, representative clinical data for training ML algorithms, while preclinical animal data is abundantly available through standardized experiments and allows for controlled induction of pathological tissue states, which is not ethically possible in patients. To leverage this situation, we propose a novel concept called "xeno-learning", a cross-species knowledge transfer paradigm inspired by xeno-transplantation, where organs from a donor species are transplanted into a recipient species. Using a total of 13,874 HSI images from humans as well as porcine and rat models, we show that although spectral signatures of organs differ substantially across species, relative changes resulting from pathologies or surgical manipulation (e.g., malperfusion; injection of contrast agent) are comparable. Such changes learnt in one species can thus be transferred to a new species via a novel "physiology-based data augmentation" method, enabling the large-scale secondary use of preclinical animal data for humans. The resulting ethical, monetary, and performance benefits promise a high impact of the proposed knowledge transfer paradigm on future developments in the field.

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arXiv2024

Understanding metric-related pitfalls in image analysis validation

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.

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arXiv2024

Metrics reloaded: Recommendations for image analysis validation

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.

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arXiv2023

Common Limitations of Image Processing Metrics: A Picture Story

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.

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arXiv2023

Unleashing the Strengths of Unlabeled Data in Pan-cancer Abdominal Organ Quantification: the FLARE22 Challenge

Quantitative organ assessment is an essential step in automated abdominal disease diagnosis and treatment planning. Artificial intelligence (AI) has shown great potential to automatize this process. However, most existing AI algorithms rely on many expert annotations and lack a comprehensive evaluation of accuracy and efficiency in real-world multinational settings. To overcome these limitations, we organized the FLARE 2022 Challenge, the largest abdominal organ analysis challenge to date, to benchmark fast, low-resource, accurate, annotation-efficient, and generalized AI algorithms. We constructed an intercontinental and multinational dataset from more than 50 medical groups, including Computed Tomography (CT) scans with different races, diseases, phases, and manufacturers. We independently validated that a set of AI algorithms achieved a median Dice Similarity Coefficient (DSC) of 90.0\% by using 50 labeled scans and 2000 unlabeled scans, which can significantly reduce annotation requirements. The best-performing algorithms successfully generalized to holdout external validation sets, achieving a median DSC of 89.5\%, 90.9\%, and 88.3\% on North American, European, and Asian cohorts, respectively. They also enabled automatic extraction of key organ biology features, which was labor-intensive with traditional manual measurements. This opens the potential to use unlabeled data to boost performance and alleviate annotation shortages for modern AI models.

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arXiv2023

Decomposition of Explained Variation in the Linear Mixed Model

In the linear mixed model (LMM), the simultaneous assessment and comparison of dispersion relevance of explanatory variables associated with fixed and random effects remains an important open practical problem. Based on the restricted maximum likelihood equations in the variance components form of the LMM, we prove a proper decomposition of the sum of squares of the dependent variable into unbiased estimators of interpretable estimands of explained variation. This result leads to a natural extension of the well-known adjusted coefficient of determination to the LMM. Further, we allocate the novel unbiased estimators of explained variation to specific contributions of covariates associated with fixed and random effects within a single model fit. These parameter-wise explained variations constitute easily interpretable quantities, assessing dispersion relevance of covariates associated with both fixed and random effects on a common scale, thus allowing for a covariate ranking. For illustration, we contrast the variation explained by subjects and time in the longitudinal sleep deprivation study. By comparing the dispersion relevance of population characteristics and spatial levels, we determine literacy as a major driver of income inequality in Burkina Faso. Finally, we develop a novel relevance plot to visualize the dispersion relevance of high-dimensional genomic markers in Arabidopsis thaliana.

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arXiv2023

Simulating and reporting frequentist operating characteristics of clinical trials that borrow external information

Borrowing of information from historical or external data to inform inference in a current trial is an expanding field in the era of precision medicine, where trials are often performed in small patient cohorts for practical or ethical reasons. Many approaches for borrowing from external data have been proposed. Even though these methods are mainly based on Bayesian approaches by incorporating external information into the prior for the current analysis, frequentist operating characteristics of the analysis strategy are of interest. In particular, type I error and power at a prespecified point alternative are in the focus. It is well-known that borrowing from external information may lead to the alteration of type I error rate. We propose a procedure to investigate and report the frequentist operating characteristics in this context. The approach evaluates type I error rate of the test with borrowing from external data and calibrates the test without borrowing to this type I error rate. On this basis, a fair comparison of power between the test with and without borrowing is achieved.

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arXiv2021

How can we learn (more) from challenges? A statistical approach to driving future algorithm development

Challenges have become the state-of-the-art approach to benchmark image analysis algorithms in a comparative manner. While the validation on identical data sets was a great step forward, results analysis is often restricted to pure ranking tables, leaving relevant questions unanswered. Specifically, little effort has been put into the systematic investigation on what characterizes images in which state-of-the-art algorithms fail. To address this gap in the literature, we (1) present a statistical framework for learning from challenges and (2) instantiate it for the specific task of instrument instance segmentation in laparoscopic videos. Our framework relies on the semantic meta data annotation of images, which serves as foundation for a General Linear Mixed Models (GLMM) analysis. Based on 51,542 meta data annotations performed on 2,728 images, we applied our approach to the results of the Robust Medical Instrument Segmentation Challenge (ROBUST-MIS) challenge 2019 and revealed underexposure, motion and occlusion of instruments as well as the presence of smoke or other objects in the background as major sources of algorithm failure. Our subsequent method development, tailored to the specific remaining issues, yielded a deep learning model with state-of-the-art overall performance and specific strengths in the processing of images in which previous methods tended to fail. Due to the objectivity and generic applicability of our approach, it could become a valuable tool for validation in the field of medical image analysis and beyond. and segmentation of small, crossing, moving and transparent instrument(s) (parts).

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arXiv2021

Machine learning-based analysis of hyperspectral images for automated sepsis diagnosis

Sepsis is a leading cause of mortality and critical illness worldwide. While robust biomarkers for early diagnosis are still missing, recent work indicates that hyperspectral imaging (HSI) has the potential to overcome this bottleneck by monitoring microcirculatory alterations. Automated machine learning-based diagnosis of sepsis based on HSI data, however, has not been explored to date. Given this gap in the literature, we leveraged an existing data set to (1) investigate whether HSI-based automated diagnosis of sepsis is possible and (2) put forth a list of possible confounders relevant for HSI-based tissue classification. While we were able to classify sepsis with an accuracy of over $98\,\%$ using the existing data, our research also revealed several subject-, therapy- and imaging-related confounders that may lead to an overestimation of algorithm performance when not balanced across the patient groups. We conclude that further prospective studies, carefully designed with respect to these confounders, are necessary to confirm the preliminary results obtained in this study.

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arXiv2021

The Medical Segmentation Decathlon

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.

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arXiv2020

Robust Medical Instrument Segmentation Challenge 2019

Intraoperative tracking of laparoscopic instruments is often a prerequisite for computer and robotic-assisted interventions. While numerous methods for detecting, segmenting and tracking of medical instruments based on endoscopic video images have been proposed in the literature, key limitations remain to be addressed: Firstly, robustness, that is, the reliable performance of state-of-the-art methods when run on challenging images (e.g. in the presence of blood, smoke or motion artifacts). Secondly, generalization; algorithms trained for a specific intervention in a specific hospital should generalize to other interventions or institutions. In an effort to promote solutions for these limitations, we organized the Robust Medical Instrument Segmentation (ROBUST-MIS) challenge as an international benchmarking competition with a specific focus on the robustness and generalization capabilities of algorithms. For the first time in the field of endoscopic image processing, our challenge included a task on binary segmentation and also addressed multi-instance detection and segmentation. The challenge was based on a surgical data set comprising 10,040 annotated images acquired from a total of 30 surgical procedures from three different types of surgery. The validation of the competing methods for the three tasks (binary segmentation, multi-instance detection and multi-instance segmentation) was performed in three different stages with an increasing domain gap between the training and the test data. The results confirm the initial hypothesis, namely that algorithm performance degrades with an increasing domain gap. While the average detection and segmentation quality of the best-performing algorithms is high, future research should concentrate on detection and segmentation of small, crossing, moving and transparent instrument(s) (parts).

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arXiv2019

Methods and open-source toolkit for analyzing and visualizing challenge results

Biomedical challenges have become the de facto standard for benchmarking biomedical image analysis algorithms. While the number of challenges is steadily increasing, surprisingly little effort has been invested in ensuring high quality design, execution and reporting for these international competitions. Specifically, results analysis and visualization in the event of uncertainties have been given almost no attention in the literature. Given these shortcomings, the contribution of this paper is two-fold: (1) We present a set of methods to comprehensively analyze and visualize the results of single-task and multi-task challenges and apply them to a number of simulated and real-life challenges to demonstrate their specific strengths and weaknesses; (2) We release the open-source framework challengeR as part of this work to enable fast and wide adoption of the methodology proposed in this paper. Our approach offers an intuitive way to gain important insights into the relative and absolute performance of algorithms, which cannot be revealed by commonly applied visualization techniques. This is demonstrated by the experiments performed within this work. Our framework could thus become an important tool for analyzing and visualizing challenge results in the field of biomedical image analysis and beyond.

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arXiv2018

Exploiting the potential of unlabeled endoscopic video data with self-supervised learning

Surgical data science is a new research field that aims to observe all aspects of the patient treatment process in order to provide the right assistance at the right time. Due to the breakthrough successes of deep learning-based solutions for automatic image annotation, the availability of reference annotations for algorithm training is becoming a major bottleneck in the field. The purpose of this paper was to investigate the concept of self-supervised learning to address this issue. Our approach is guided by the hypothesis that unlabeled video data can be used to learn a representation of the target domain that boosts the performance of state-of-the-art machine learning algorithms when used for pre-training. Core of the method is an auxiliary task based on raw endoscopic video data of the target domain that is used to initialize the convolutional neural network (CNN) for the target task. In this paper, we propose the re-colorization of medical images with a generative adversarial network (GAN)-based architecture as auxiliary task. A variant of the method involves a second pre-training step based on labeled data for the target task from a related domain. We validate both variants using medical instrument segmentation as target task. The proposed approach can be used to radically reduce the manual annotation effort involved in training CNNs. Compared to the baseline approach of generating annotated data from scratch, our method decreases exploratively the number of labeled images by up to 75% without sacrificing performance. Our method also outperforms alternative methods for CNN pre-training, such as pre-training on publicly available non-medical or medical data using the target task (in this instance: segmentation). As it makes efficient use of available (non-)public and (un-)labeled data, the approach has the potential to become a valuable tool for CNN (pre-)training.

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