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How can we test AI performance? This question seems trivial, but it isn't. Standard benchmarks often have problems such as in-distribution and small-size test sets, oversimplified metrics, unfair comparisons, and short-term outcome pressure. As a consequence, good performance on standard benchmarks does not guarantee success in real-world scenarios. To address these problems, we present Touchstone, a large-scale collaborative segmentation benchmark of 9 types of abdominal organs. This benchmark is based on 5,195 training CT scans from 76 hospitals around the world and 5,903 testing CT scans from 11 additional hospitals. This diverse test set enhances the statistical significance of benchmark results and rigorously evaluates AI algorithms across various out-of-distribution scenarios. We invited 14 inventors of 19 AI algorithms to train their algorithms, while our team, as a third party, independently evaluated these algorithms on three test sets. In addition, we also evaluated pre-existing AI frameworks--which, differing from algorithms, are more flexible and can support different algorithms--including MONAI from NVIDIA, nnU-Net from DKFZ, and numerous other open-source frameworks. We are committed to expanding this benchmark to encourage more innovation of AI algorithms for the medical domain., Comment: Accepted to NeurIPS-2024

What representation do deep neural networks learn? How similar are images to each other for neural networks? Despite the overwhelming success of deep learning methods key questions about their internal workings still remain largely unanswered, due to their internal high dimensionality and complexity. To address this, one approach is to measure the similarity of activation responses to various inputs. Representational Similarity Matrices (RSMs) distill this similarity into scalar values for each input pair. These matrices encapsulate the entire similarity structure of a system, indicating which input leads to similar responses. While the similarity between images is ambiguous, we argue that the spatial location of semantic objects does neither influence human perception nor deep learning classifiers. Thus this should be reflected in the definition of similarity between image responses for computer vision systems. Revisiting the established similarity calculations for RSMs we expose their sensitivity to spatial alignment. In this paper, we propose to solve this through semantic RSMs, which are invariant to spatial permutation. We measure semantic similarity between input responses by formulating it as a set-matching problem. Further, we quantify the superiority of semantic RSMs over spatio-semantic RSMs through image retrieval and by comparing the similarity between representations to the similarity between predicted class probabilities., Comment: Accepted at NeurIPS2024

Accurate segmentation of Multiple Sclerosis (MS) lesions in longitudinal MRI scans is crucial for monitoring disease progression and treatment efficacy. Although changes across time are taken into account when assessing images in clinical practice, most existing deep learning methods treat scans from different timepoints separately. Among studies utilizing longitudinal images, a simple channel-wise concatenation is the primary albeit suboptimal method employed to integrate timepoints. We introduce a novel approach that explicitly incorporates temporal differences between baseline and follow-up scans through a unique architectural inductive bias called Difference Weighting Block. It merges features from two timepoints, emphasizing changes between scans. We achieve superior scores in lesion segmentation (Dice Score, Hausdorff distance) as well as lesion detection (lesion-level $F_1$ score) as compared to state-of-the-art longitudinal and single timepoint models across two datasets. Our code is made publicly available at www.github.com/MIC-DKFZ/Longitudinal-Difference-Weighting., Comment: Accepted at MICCAI 2024 LDTM

The third autoPET challenge introduced a new data-centric task this year, shifting the focus from model development to improving metastatic lesion segmentation on PET/CT images through data quality and handling strategies. In response, we developed targeted methods to enhance segmentation performance tailored to the characteristics of PET/CT imaging. Our approach encompasses two key elements. First, to address potential alignment errors between CT and PET modalities as well as the prevalence of punctate lesions, we modified the baseline data augmentation scheme and extended it with misalignment augmentation. This adaptation aims to improve segmentation accuracy, particularly for tiny metastatic lesions. Second, to tackle the variability in image dimensions significantly affecting the prediction time, we implemented a dynamic ensembling and test-time augmentation (TTA) strategy. This method optimizes the use of ensembling and TTA within a 5-minute prediction time limit, effectively leveraging the generalization potential for both small and large images. Both of our solutions are designed to be robust across different tracers and institutional settings, offering a general, yet imaging-specific approach to the multi-tracer and multi-institutional challenges of the competition. We made the challenge repository with our modifications publicly available at \url{https://github.com/MIC-DKFZ/miccai2024_autopet3_datacentric}., Comment: Contribution to the data-centric task of the autoPET III Challenge 2024

Automated lesion segmentation in PET/CT scans is crucial for improving clinical workflows and advancing cancer diagnostics. However, the task is challenging due to physiological variability, different tracers used in PET imaging, and diverse imaging protocols across medical centers. To address this, the autoPET series was created to challenge researchers to develop algorithms that generalize across diverse PET/CT environments. This paper presents our solution for the autoPET III challenge, targeting multitracer, multicenter generalization using the nnU-Net framework with the ResEncL architecture. Key techniques include misalignment data augmentation and multi-modal pretraining across CT, MR, and PET datasets to provide an initial anatomical understanding. We incorporate organ supervision as a multitask approach, enabling the model to distinguish between physiological uptake and tracer-specific patterns, which is particularly beneficial in cases where no lesions are present. Compared to the default nnU-Net, which achieved a Dice score of 57.61, or the larger ResEncL (65.31) our model significantly improved performance with a Dice score of 68.40, alongside a reduction in false positive (FPvol: 7.82) and false negative (FNvol: 10.35) volumes. These results underscore the effectiveness of combining advanced network design, augmentation, pretraining, and multitask learning for PET/CT lesion segmentation. After evaluation on the test set, our approach was awarded the first place in the model-centric category (Team LesionTracer). Code is publicly available at https://github.com/MIC-DKFZ/autopet-3-submission., Comment: Winning method of the autoPET III challenge (model-centric) - Team LesionTracer

This paper does not describe a novel method. Instead, it studies an essential foundation for reliable benchmarking and ultimately real-world application of AI-based image analysis: generating high-quality reference annotations. Previous research has focused on crowdsourcing as a means of outsourcing annotations. However, little attention has so far been given to annotation companies, specifically regarding their internal quality assurance (QA) processes. Therefore, our aim is to evaluate the influence of QA employed by annotation companies on annotation quality and devise methodologies for maximizing data annotation efficacy. Based on a total of 57,648 instance segmented images obtained from a total of 924 annotators and 34 QA workers from four annotation companies and Amazon Mechanical Turk (MTurk), we derived the following insights: (1) Annotation companies perform better both in terms of quantity and quality compared to the widely used platform MTurk. (2) Annotation companies' internal QA only provides marginal improvements, if any. However, improving labeling instructions instead of investing in QA can substantially boost annotation performance. (3) The benefit of internal QA depends on specific image characteristics. Our work could enable researchers to derive substantially more value from a fixed annotation budget and change the way annotation companies conduct internal QA., Comment: Accepted at ECCV 2024, preprint, Computer Vision, Data Annotation

Semantic segmentation is an essential component of medical image analysis research, with recent deep learning algorithms offering out-of-the-box applicability across diverse datasets. Despite these advancements, segmentation failures remain a significant concern for real-world clinical applications, necessitating reliable detection mechanisms. This paper introduces a comprehensive benchmarking framework aimed at evaluating failure detection methodologies within medical image segmentation. Through our analysis, we identify the strengths and limitations of current failure detection metrics, advocating for the risk-coverage analysis as a holistic evaluation approach. Utilizing a collective dataset comprising five public 3D medical image collections, we assess the efficacy of various failure detection strategies under realistic test-time distribution shifts. Our findings highlight the importance of pixel confidence aggregation and we observe superior performance of the pairwise Dice score (Roy et al., 2019) between ensemble predictions, positioning it as a simple and robust baseline for failure detection in medical image segmentation. To promote ongoing research, we make the benchmarking framework available to the community., Comment: This work has been submitted for possible publication

Despite considerable strides in developing deep learning models for 3D medical image segmentation, the challenge of effectively generalizing across diverse image distributions persists. While domain generalization is acknowledged as vital for robust application in clinical settings, the challenges stemming from training with a limited Field of View (FOV) remain unaddressed. This limitation leads to false predictions when applied to body regions beyond the FOV of the training data. In response to this problem, we propose a novel loss function that penalizes predictions in implausible body regions, applicable in both single-dataset and multi-dataset training schemes. It is realized with a Body Part Regression model that generates axial slice positional scores. Through comprehensive evaluation using a test set featuring varying FOVs, our approach demonstrates remarkable improvements in generalization capabilities. It effectively mitigates false positive tumor predictions up to 85% and significantly enhances overall segmentation performance.

The release of nnU-Net marked a paradigm shift in 3D medical image segmentation, demonstrating that a properly configured U-Net architecture could still achieve state-of-the-art results. Despite this, the pursuit of novel architectures, and the respective claims of superior performance over the U-Net baseline, continued. In this study, we demonstrate that many of these recent claims fail to hold up when scrutinized for common validation shortcomings, such as the use of inadequate baselines, insufficient datasets, and neglected computational resources. By meticulously avoiding these pitfalls, we conduct a thorough and comprehensive benchmarking of current segmentation methods including CNN-based, Transformer-based, and Mamba-based approaches. In contrast to current beliefs, we find that the recipe for state-of-the-art performance is 1) employing CNN-based U-Net models, including ResNet and ConvNeXt variants, 2) using the nnU-Net framework, and 3) scaling models to modern hardware resources. These results indicate an ongoing innovation bias towards novel architectures in the field and underscore the need for more stringent validation standards in the quest for scientific progress., Comment: Accepted at MICCAI 2024

Accurately segmenting thin tubular structures, such as vessels, nerves, roads or concrete cracks, is a crucial task in computer vision. Standard deep learning-based segmentation loss functions, such as Dice or Cross-Entropy, focus on volumetric overlap, often at the expense of preserving structural connectivity or topology. This can lead to segmentation errors that adversely affect downstream tasks, including flow calculation, navigation, and structural inspection. Although current topology-focused losses mark an improvement, they introduce significant computational and memory overheads. This is particularly relevant for 3D data, rendering these losses infeasible for larger volumes as well as increasingly important multi-class segmentation problems. To mitigate this, we propose a novel Skeleton Recall Loss, which effectively addresses these challenges by circumventing intensive GPU-based calculations with inexpensive CPU operations. It demonstrates overall superior performance to current state-of-the-art approaches on five public datasets for topology-preserving segmentation, while substantially reducing computational overheads by more than 90%. In doing so, we introduce the first multi-class capable loss function for thin structure segmentation, excelling in both efficiency and efficacy for topology-preservation., Comment: Accepted at ECCV 2024

Traditionally, segmentation algorithms require dense annotations for training, demanding significant annotation efforts, particularly within the 3D medical imaging field. Scribble-supervised learning emerges as a possible solution to this challenge, promising a reduction in annotation efforts when creating large-scale datasets. Recently, a plethora of methods for optimized learning from scribbles have been proposed, but have so far failed to position scribble annotation as a beneficial alternative. We relate this shortcoming to two major issues: 1) the complex nature of many methods which deeply ties them to the underlying segmentation model, thus preventing a migration to more powerful state-of-the-art models as the field progresses and 2) the lack of a systematic evaluation to validate consistent performance across the broader medical domain, resulting in a lack of trust when applying these methods to new segmentation problems. To address these issues, we propose a comprehensive scribble supervision benchmark consisting of seven datasets covering a diverse set of anatomies and pathologies imaged with varying modalities. We furthermore propose the systematic use of partial losses, i.e. losses that are only computed on annotated voxels. Contrary to most existing methods, these losses can be seamlessly integrated into state-of-the-art segmentation methods, enabling them to learn from scribble annotations while preserving their original loss formulations. Our evaluation using nnU-Net reveals that while most existing methods suffer from a lack of generalization, the proposed approach consistently delivers state-of-the-art performance. Thanks to its simplicity, our approach presents an embarrassingly simple yet effective solution to the challenges of scribble supervision. Source code as well as our extensive scribble benchmarking suite will be made publicly available upon publication.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically., Comment: 24 pages, 11 figures, 9 tables. Summary Paper for the MICCAI TopCoW 2023 Challenge

This paper introduces panoptica, a versatile and performance-optimized package designed for computing instance-wise segmentation quality metrics from 2D and 3D segmentation maps. panoptica addresses the limitations of existing metrics and provides a modular framework that complements the original intersection over union-based panoptic quality with other metrics, such as the distance metric Average Symmetric Surface Distance. The package is open-source, implemented in Python, and accompanied by comprehensive documentation and tutorials. panoptica employs a three-step metrics computation process to cover diverse use cases. The efficacy of panoptica is demonstrated on various real-world biomedical datasets, where an instance-wise evaluation is instrumental for an accurate representation of the underlying clinical task. Overall, we envision panoptica as a valuable tool facilitating in-depth evaluation of segmentation methods., Comment: 15 pages, 6 figures, 3 tables

We participate in the AutoPET II challenge by modifying nnU-Net only through its easy to understand and modify 'nnUNetPlans.json' file. By switching to a UNet with residual encoder, increasing the batch size and increasing the patch size we obtain a configuration that substantially outperforms the automatically configured nnU-Net baseline (5-fold cross-validation Dice score of 65.14 vs 33.28) at the expense of increased compute requirements for model training. Our final submission ensembles the two most promising configurations.

Despite the remarkable success of deep learning systems over the last decade, a key difference still remains between neural network and human decision-making: As humans, we cannot only form a decision on the spot, but also ponder, revisiting an initial guess from different angles, distilling relevant information, arriving at a better decision. Here, we propose RecycleNet, a latent feature recycling method, instilling the pondering capability for neural networks to refine initial decisions over a number of recycling steps, where outputs are fed back into earlier network layers in an iterative fashion. This approach makes minimal assumptions about the neural network architecture and thus can be implemented in a wide variety of contexts. Using medical image segmentation as the evaluation environment, we show that latent feature recycling enables the network to iteratively refine initial predictions even beyond the iterations seen during training, converging towards an improved decision. We evaluate this across a variety of segmentation benchmarks and show consistent improvements even compared with top-performing segmentation methods. This allows trading increased computation time for improved performance, which can be beneficial, especially for safety-critical applications., Comment: Accepted at 2024 Winter Conference on Applications of Computer Vision (WACV)

Data augmentation (DA) is a key factor in medical image analysis, such as in prostate cancer (PCa) detection on magnetic resonance images. State-of-the-art computer-aided diagnosis systems still rely on simplistic spatial transformations to preserve the pathological label post transformation. However, such augmentations do not substantially increase the organ as well as tumor shape variability in the training set, limiting the model's ability to generalize to unseen cases with more diverse localized soft-tissue deformations. We propose a new anatomy-informed transformation that leverages information from adjacent organs to simulate typical physiological deformations of the prostate and generates unique lesion shapes without altering their label. Due to its lightweight computational requirements, it can be easily integrated into common DA frameworks. We demonstrate the effectiveness of our augmentation on a dataset of 774 biopsy-confirmed examinations, by evaluating a state-of-the-art method for PCa detection with different augmentation settings., Comment: Accepted at MICCAI 2023

Independently trained machine learning models tend to learn similar features. Given an ensemble of independently trained models, this results in correlated predictions and common failure modes. Previous attempts focusing on decorrelation of output predictions or logits yielded mixed results, particularly due to their reduction in model accuracy caused by conflicting optimization objectives. In this paper, we propose the novel idea of utilizing methods of the representational similarity field to promote dissimilarity during training instead of measuring similarity of trained models. To this end, we promote intermediate representations to be dissimilar at different depths between architectures, with the goal of learning robust ensembles with disjoint failure modes. We show that highly dissimilar intermediate representations result in less correlated output predictions and slightly lower error consistency, resulting in higher ensemble accuracy. With this, we shine first light on the connection between intermediate representations and their impact on the output predictions., Comment: The Second Workshop on Spurious Correlations, Invariance and Stability at ICML 2023

This paper presents the challenge report for the 2021 Kidney and Kidney Tumor Segmentation Challenge (KiTS21) held in conjunction with the 2021 international conference on Medical Image Computing and Computer Assisted Interventions (MICCAI). KiTS21 is a sequel to its first edition in 2019, and it features a variety of innovations in how the challenge was designed, in addition to a larger dataset. A novel annotation method was used to collect three separate annotations for each region of interest, and these annotations were performed in a fully transparent setting using a web-based annotation tool. Further, the KiTS21 test set was collected from an outside institution, challenging participants to develop methods that generalize well to new populations. Nonetheless, the top-performing teams achieved a significant improvement over the state of the art set in 2019, and this performance is shown to inch ever closer to human-level performance. An in-depth meta-analysis is presented describing which methods were used and how they faired on the leaderboard, as well as the characteristics of which cases generally saw good performance, and which did not. Overall KiTS21 facilitated a significant advancement in the state of the art in kidney tumor segmentation, and provides useful insights that are applicable to the field of semantic segmentation as a whole., Comment: 34 pages, 12 figures

Owing to success in the data-rich domain of natural images, Transformers have recently become popular in medical image segmentation. However, the pairing of Transformers with convolutional blocks in varying architectural permutations leaves their relative effectiveness to open interpretation. We introduce Transformer Ablations that replace the Transformer blocks with plain linear operators to quantify this effectiveness. With experiments on 8 models on 2 medical image segmentation tasks, we explore -- 1) the replaceable nature of Transformer-learnt representations, 2) Transformer capacity alone cannot prevent representational replaceability and works in tandem with effective design, 3) The mere existence of explicit feature hierarchies in transformer blocks is more beneficial than accompanying self-attention modules, 4) Major spatial downsampling before Transformer modules should be used with caution., Comment: Accepted in NeurIPS 2022 workshop, Medical Imaging Meets NeurIPS (MedNeurIPS)

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work., Comment: accepted to CVPR 2023

The medical imaging community generates a wealth of datasets, many of which are openly accessible and annotated for specific diseases and tasks such as multi-organ or lesion segmentation. Current practices continue to limit model training and supervised pre-training to one or a few similar datasets, neglecting the synergistic potential of other available annotated data. We propose MultiTalent, a method that leverages multiple CT datasets with diverse and conflicting class definitions to train a single model for a comprehensive structure segmentation. Our results demonstrate improved segmentation performance compared to previous related approaches, systematically, also compared to single dataset training using state-of-the-art methods, especially for lesion segmentation and other challenging structures. We show that MultiTalent also represents a powerful foundation model that offers a superior pre-training for various segmentation tasks compared to commonly used supervised or unsupervised pre-training baselines. Our findings offer a new direction for the medical imaging community to effectively utilize the wealth of available data for improved segmentation performance. The code and model weights will be published here: [tba], Comment: Accepted for Miccai 2023 and selected for an oral

There has been exploding interest in embracing Transformer-based architectures for medical image segmentation. However, the lack of large-scale annotated medical datasets make achieving performances equivalent to those in natural images challenging. Convolutional networks, in contrast, have higher inductive biases and consequently, are easily trainable to high performance. Recently, the ConvNeXt architecture attempted to modernize the standard ConvNet by mirroring Transformer blocks. In this work, we improve upon this to design a modernized and scalable convolutional architecture customized to challenges of data-scarce medical settings. We introduce MedNeXt, a Transformer-inspired large kernel segmentation network which introduces - 1) A fully ConvNeXt 3D Encoder-Decoder Network for medical image segmentation, 2) Residual ConvNeXt up and downsampling blocks to preserve semantic richness across scales, 3) A novel technique to iteratively increase kernel sizes by upsampling small kernel networks, to prevent performance saturation on limited medical data, 4) Compound scaling at multiple levels (depth, width, kernel size) of MedNeXt. This leads to state-of-the-art performance on 4 tasks on CT and MRI modalities and varying dataset sizes, representing a modernized deep architecture for medical image segmentation. Our code is made publicly available at: https://github.com/MIC-DKFZ/MedNeXt., Comment: Accepted at MICCAI 2023

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., Comment: Shared first authors: Annika Reinke and Minu D. Tizabi; shared senior authors: Lena Maier-Hein and Paul F. J\"ager. Published in Nature Methods. arXiv admin note: text overlap with arXiv:2206.01653

Minerals, metals, and plastics are indispensable for a functioning modern society. Yet, their supply is limited causing a need for optimizing ore extraction and recuperation from recyclable materials.Typically, those processes must be meticulously adapted to the precise properties of the processed materials. Advancing our understanding of these materials is thus vital and can be achieved by crushing them into particles of micrometer size followed by their characterization. Current imaging approaches perform this analysis based on segmentation and characterization of particles imaged with computed tomography (CT), and rely on rudimentary postprocessing techniques to separate touching particles. However, their inability to reliably perform this separation as well as the need to retrain methods for each new image, these approaches leave untapped potential to be leveraged. Here, we propose ParticleSeg3D, an instance segmentation method able to extract individual particles from large CT images of particle samples containing different materials. Our approach is based on the powerful nnU-Net framework, introduces a particle size normalization, uses a border-core representation to enable instance segmentation, and is trained with a large dataset containing particles of numerous different sizes, shapes, and compositions of various materials. We demonstrate that ParticleSeg3D can be applied out-of-the-box to a large variety of particle types, including materials and appearances that have not been part of the training set. Thus, no further manual annotations and retraining are required when applying the method to new particle samples, enabling substantially higher scalability of experiments than existing methods. Our code and dataset are made publicly available.

Unsupervised anomaly detection in medical imaging aims to detect and localize arbitrary anomalies without requiring annotated anomalous data during training. Often, this is achieved by learning a data distribution of normal samples and detecting anomalies as regions in the image which deviate from this distribution. Most current state-of-the-art methods use latent variable generative models operating directly on the images. However, generative models have been shown to mostly capture low-level features, s.a. pixel-intensities, instead of rich semantic features, which also applies to their representations. We circumvent this problem by proposing CRADL whose core idea is to model the distribution of normal samples directly in the low-dimensional representation space of an encoder trained with a contrastive pretext-task. By utilizing the representations of contrastive learning, we aim to fix the over-fixation on low-level features and learn more semantic-rich representations. Our experiments on anomaly detection and localization tasks using three distinct evaluation datasets show that 1) contrastive representations are superior to representations of generative latent variable models and 2) the CRADL framework shows competitive or superior performance to state-of-the-art.

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.

With the rise of AI in recent years and the increase in complexity of the models, the growing demand in computational resources is starting to pose a significant challenge. The need for higher compute power is being met with increasingly more potent accelerators and the use of large compute clusters. However, the gain in prediction accuracy from large models trained on distributed and accelerated systems comes at the price of a substantial increase in energy demand, and researchers have started questioning the environmental friendliness of such AI methods at scale. Consequently, energy efficiency plays an important role for AI model developers and infrastructure operators alike. The energy consumption of AI workloads depends on the model implementation and the utilized hardware. Therefore, accurate measurements of the power draw of AI workflows on different types of compute nodes is key to algorithmic improvements and the design of future compute clusters and hardware. To this end, we present measurements of the energy consumption of two typical applications of deep learning models on different types of compute nodes. Our results indicate that 1. deriving energy consumption directly from runtime is not accurate, but the consumption of the compute node needs to be considered regarding its composition; 2. neglecting accelerator hardware on mixed nodes results in overproportional inefficiency regarding energy consumption; 3. energy consumption of model training and inference should be considered separately - while training on GPUs outperforms all other node types regarding both runtime and energy consumption, inference on CPU nodes can be comparably efficient. One advantage of our approach is that the information on energy consumption is available to all users of the supercomputer, enabling an easy transfer to other workloads alongside a raise in user-awareness of energy consumption., Comment: Submitted to HPC on Heterogeneous Hardware (H3) in Lecture Notes in Computer Science

Performance metrics for medical image segmentation models are used to measure the agreement between the reference annotation and the predicted segmentation. Usually, overlap metrics, such as the Dice, are used as a metric to evaluate the performance of these models in order for results to be comparable. However, there is a mismatch between the distributions of cases and difficulty level of segmentation tasks in public data sets compared to clinical practice. Common metrics fail to measure the impact of this mismatch, especially for clinical data sets that include low signal pathologies, a difficult segmentation task, and uncertain, small, or empty reference annotations. This limitation may result in ineffective research of machine learning practitioners in designing and optimizing models. Dimensions of evaluating clinical value include consideration of the uncertainty of reference annotations, independence from reference annotation volume size, and evaluation of classification of empty reference annotations. We study how uncertain, small, and empty reference annotations influence the value of metrics for medical image segmentation on an in-house data set regardless of the model. We examine metrics behavior on the predictions of a standard deep learning framework in order to identify metrics with clinical value. We compare to a public benchmark data set (BraTS 2019) with a high-signal pathology and certain, larger, and no empty reference annotations. We may show machine learning practitioners, how uncertain, small, or empty reference annotations require a rethinking of the evaluation and optimizing procedures. The evaluation code was released to encourage further analysis of this topic. https://github.com/SophieOstmeier/UncertainSmallEmpty.git, Comment: 16 pages, 10 figures, Published in Medical Image Analysis

Semantic segmentation is one of the most popular research areas in medical image computing. Perhaps surprisingly, despite its conceptualization dating back to 2018, nnU-Net continues to provide competitive out-of-the-box solutions for a broad variety of segmentation problems and is regularly used as a development framework for challenge-winning algorithms. Here we use nnU-Net to participate in the AMOS2022 challenge, which comes with a unique set of tasks: not only is the dataset one of the largest ever created and boasts 15 target structures, but the competition also requires submitted solutions to handle both MRI and CT scans. Through careful modification of nnU-net's hyperparameters, the addition of residual connections in the encoder and the design of a custom postprocessing strategy, we were able to substantially improve upon the nnU-Net baseline. Our final ensemble achieves Dice scores of 90.13 for Task 1 (CT) and 89.06 for Task 2 (CT+MRI) in a 5-fold cross-validation on the provided training cases., Comment: Fabian Isensee, Constantin Ulrich and Tassilo Wald contributed equally

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., Comment: Shared first authors: Lena Maier-Hein, Annika Reinke. arXiv admin note: substantial text overlap with arXiv:2104.05642 Published in Nature Methods

Single particle imaging (SPI) at X-ray free electron lasers (XFELs) is particularly well suited to determine the 3D structure of particles in their native environment. For a successful reconstruction, diffraction patterns originating from a single hit must be isolated from a large number of acquired patterns. We propose to formulate this task as an image classification problem and solve it using convolutional neural network (CNN) architectures. Two CNN configurations are developed: one that maximises the F1-score and one that emphasises high recall. We also combine the CNNs with expectation maximization (EM) selection as well as size filtering. We observed that our CNN selections have lower contrast in power spectral density functions relative to the EM selection, used in our previous work. However, the reconstruction of our CNN-based selections gives similar results. Introducing CNNs into SPI experiments allows streamlining the reconstruction pipeline, enables researchers to classify patterns on the fly, and, as a consequence, enables them to tightly control the duration of their experiments. We think that bringing non-standard artificial intelligence (AI) based solutions in a well-described SPI analysis workflow may be beneficial for the future development of the SPI experiments., Comment: Main text: 28 pages, 7 figures, Supporting Information: 12 pages, 6 figures

The ability to estimate how a tumor might evolve in the future could have tremendous clinical benefits, from improved treatment decisions to better dose distribution in radiation therapy. Recent work has approached the glioma growth modeling problem via deep learning and variational inference, thus learning growth dynamics entirely from a real patient data distribution. So far, this approach was constrained to predefined image acquisition intervals and sequences of fixed length, which limits its applicability in more realistic scenarios. We overcome these limitations by extending Neural Processes, a class of conditional generative models for stochastic time series, with a hierarchical multi-scale representation encoding including a spatio-temporal attention mechanism. The result is a learned growth model that can be conditioned on an arbitrary number of observations, and that can produce a distribution of temporally consistent growth trajectories on a continuous time axis. On a dataset of 379 patients, the approach successfully captures both global and finer-grained variations in the images, exhibiting superior performance compared to other learned growth models., Comment: MICCAI 2021

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).

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.

Neural Processes (NPs) are a family of conditional generative models that are able to model a distribution over functions, in a way that allows them to perform predictions at test time conditioned on a number of context points. A recent addition to this family, Convolutional Conditional Neural Processes (ConvCNP), have shown remarkable improvement in performance over prior art, but we find that they sometimes struggle to generalize when applied to time series data. In particular, they are not robust to distribution shifts and fail to extrapolate observed patterns into the future. By incorporating a Gaussian Process into the model, we are able to remedy this and at the same time improve performance within distribution. As an added benefit, the Gaussian Process reintroduces the possibility to sample from the model, a key feature of other members in the NP family., Comment: UAI 2021

Simultaneous localisation and categorization of objects in medical images, also referred to as medical object detection, is of high clinical relevance because diagnostic decisions often depend on rating of objects rather than e.g. pixels. For this task, the cumbersome and iterative process of method configuration constitutes a major research bottleneck. Recently, nnU-Net has tackled this challenge for the task of image segmentation with great success. Following nnU-Net's agenda, in this work we systematize and automate the configuration process for medical object detection. The resulting self-configuring method, nnDetection, adapts itself without any manual intervention to arbitrary medical detection problems while achieving results en par with or superior to the state-of-the-art. We demonstrate the effectiveness of nnDetection on two public benchmarks, ADAM and LUNA16, and propose 11 further medical object detection tasks on public data sets for comprehensive method evaluation. Code is at https://github.com/MIC-DKFZ/nnDetection ., Comment: MICCAI 2021 (splitted LN data set for camera-ready version); *Michael Baumgartner and Paul F. J\"ager contributed equally

Photoacoustic (PA) imaging has the potential to revolutionize functional medical imaging in healthcare due to the valuable information on tissue physiology contained in multispectral photoacoustic measurements. Clinical translation of the technology requires conversion of the high-dimensional acquired data into clinically relevant and interpretable information. In this work, we present a deep learning-based approach to semantic segmentation of multispectral photoacoustic images to facilitate image interpretability. Manually annotated photoacoustic {and ultrasound} imaging data are used as reference and enable the training of a deep learning-based segmentation algorithm in a supervised manner. Based on a validation study with experimentally acquired data from 16 healthy human volunteers, we show that automatic tissue segmentation can be used to create powerful analyses and visualizations of multispectral photoacoustic images. Due to the intuitive representation of high-dimensional information, such a preprocessing algorithm could be a valuable means to facilitate the clinical translation of photoacoustic imaging., Comment: 8 pages, 7 figures, 3 tables

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., Comment: Shared first authors: Annika Reinke and Minu D. Tizabi. This is a dynamic paper on limitations of commonly used metrics. It discusses metrics for image-level classification, semantic and instance segmentation, and object detection. For missing use cases, comments or questions, please contact a.reinke@dkfz.de. Substantial contributions to this document will be acknowledged with a co-authorship