Research Group Daniel Rückert

Topological correctness, i.e., the preservation of structural integrity and specific characteristics of shape, is a fundamental requirement for medical imaging tasks, such as neuron or vessel segmentation. Despite the recent surge in topology-aware methods addressing this challenge, their real-world applicability is hindered by flawed benchmarking practices. In this paper, we identify critical pitfalls in model evaluation that include inadequate connectivity choices, overlooked topological artifacts in ground truth annotations, and inappropriate use of evaluation metrics. Through detailed empirical analysis, we uncover these issues’ profound impact on the evaluation and ranking of segmentation methods. Drawing from our findings, we propose a set of actionable recommendations to establish fair and robust evaluation standards for topology-aware medical image segmentation methods.

Current AI frameworks for brain decoding and encoding, typically train and test models within the same datasets. This limits their utility for brain computer interfaces (BCI) or neurofeedback, for which it would be useful to pool experiences across individuals to better simulate stimuli not sampled during training. A key obstacle to model generalisation is the degree of variability of inter-subject cortical organisation, which makes it difficult to align or compare cortical signals across participants. In this paper we address this through the use of surface vision transformers, which build a generalisable model of cortical functional dynamics, through encoding the topography of cortical networks and their interactions as a moving image across a surface. This is then combined with tri-modal self-supervised contrastive (CLIP) alignment of audio, video, and fMRI modalities to enable the retrieval of visual and auditory stimuli from patterns of cortical activity (and vice-versa). We validate our approach on 7T task-fMRI data from 174 healthy participants engaged in the movie-watching experiment from the Human Connectome Project (HCP). Results show that it is possible to detect which movie clips an individual is watching purely from their brain activity, even for individuals and movies not seen during training. Further analysis of attention maps reveals that our model captures individual patterns of brain activity that reflect semantic and visual systems. This opens the door to future personalised simulations of brain function.

Topological correctness plays a critical role in many image segmentation tasks, yet most networks are trained using pixel-wise loss functions, such as Dice, neglecting topological accuracy. Existing topology-aware methods often lack robust topological guarantees, are limited to specific use cases, or impose high computational costs. In this work, we propose a novel, graph-based framework for topologically accurate image segmentation that is both computationally efficient and generally applicable. Our method constructs a component graph that fully encodes the topological information of both the prediction and ground truth, allowing us to efficiently identify topologically critical regions and aggregate a loss based on local neighborhood information. Furthermore, we introduce a strict topological metric capturing the homotopy equivalence between the union and intersection of prediction-label pairs. We formally prove the topological guarantees of our approach and empirically validate its effectiveness on binary and multi-class datasets. Our loss demonstrates state-of-the-art performance with up to fivefold faster loss computation compared to persistent homology methods.

Cardiovascular diseases (CVD) can be diagnosed using various diagnostic modalities. The electrocardiogram (ECG) is a cost-effective and widely available diagnostic aid that provides functional information of the heart. However, its ability to classify and spatially localise CVD is limited. In contrast, cardiac magnetic resonance (CMR) imaging provides detailed structural information of the heart and thus enables evidence-based diagnosis of CVD, but long scan times and high costs limit its use in clinical routine. In this work, we present a deep learning strategy for cost-effective and comprehensive cardiac screening solely from ECG. Our approach combines multimodal contrastive learning with masked data modelling to transfer domain-specific information from CMR imaging to ECG representations. In extensive experiments using data from 40,044 UK Biobank subjects, we demonstrate the utility and generalisability of our method for subject-specific risk prediction of CVD and the prediction of cardiac phenotypes using only ECG data. Specifically, our novel multimodal pre-training paradigm improves performance by up to 12.19% for risk prediction and 27.59% for phenotype prediction. In a qualitative analysis, we demonstrate that our learned ECG representations incorporate information from CMR image regions of interest.

In this paper, we propose a methodology for extracting molecular tumor biomarkers from hyperspectral imaging (HSI), an emerging technology for intraoperative tissue assessment. To achieve this, we employ spectral unmixing, allowing to decompose the spectral signals recorded by the HSI camera into their constituent molecular components. Traditional unmixing approaches are based on physical models that establish a relationship between tissue molecules and the recorded spectra. However, these methods commonly assume a linear relationship between the spectra and molecular content, which does not capture the whole complexity of light-matter interaction. To address this limitation, we introduce a novel unmixing procedure that allows to take into account non-linear optical effects while preserving the computational benefits of linear spectral unmixing. We validate our methodology on an in-vivo brain tissue HSI dataset and demonstrate that the extracted molecular information leads to superior classification performance.

Supervised contrastive learning (SupCon) has proven to be a powerful alternative to the standard cross-entropy loss for classification of multi-class balanced datasets. However, it struggles to learn well-conditioned representations of datasets with long-tailed class distributions. This problem is potentially exacerbated for binary imbalanced distributions, which are commonly encountered during many real-world problems such as medical diagnosis. In experiments on seven binary datasets of natural and medical images, we show that the performance of SupCon decreases with increasing class imbalance. To substantiate these findings, we introduce two novel metrics that evaluate the quality of the learned representation space. By measuring the class distribution in local neighborhoods, we are able to uncover structural deficiencies of the representation space that classical metrics cannot detect. Informed by these insights, we propose two new supervised contrastive learning strategies tailored to binary imbalanced datasets that improve the structure of the representation space and increase downstream classification accuracy over standard SupCon by up to 35%. We make our code available.

Evaluating deformable image registration (DIR) is challenging due to the inherent trade-off between achieving high alignment accuracy and maintaining deformation regularity. In this work, we introduce a novel evaluation scheme based on the alignment-regularity characteristic (ARC) to systematically capture and analyze this trade-off. We first introduce the ARC curves, which describe the performance of a given registration algorithm as a spectrum measured by alignment and regularity metrics. We further adopt a HyperNetwork-based approach that learns to continuously interpolate across the full regularization range, accelerating the construction and improving the sample density of ARC curves. We empirically demonstrate our evaluation scheme using representative learning-based deformable image registration methods with various network architectures and transformation models on two public datasets. We present a range of findings not evident from existing evaluation practices and provide general recommendations for model evaluation and selection using our evaluation scheme. All code relevant is made publicly available.

The histopathological classification of whole-slide images (WSIs) is a fundamental task in digital pathology; yet it requires extensive time and expertise from specialists. While deep learning methods show promising results, they typically process WSIs by dividing them into artificial patches, which inherently prevents a network from learning from the entire image context, disregards natural tissue structures and compromises interpretability. Our method overcomes this limitation through a novel graph-based framework that constructs WSI graph representations. The WSI-graph efficiently captures essential histopathological information in a compact form. We build tissue representations (nodes) that follow biological boundaries rather than arbitrary patches all while providing interpretable features for explainability. Through adaptive graph coarsening guided by learned embeddings, we progressively merge regions while maintaining discriminative local features and enabling efficient global information exchange. In our method’s final step, we solve the diagnostic task through a graph attention network. We empirically demonstrate strong performance on multiple challenging tasks such as cancer stage classification and survival prediction, while also identifying predictive factors using Integrated Gradients.

Direct image-to-graph transformation is a challenging task that involves solving object detection and relationship prediction in a single model. Due to this task’s complexity, large training datasets are rare in many domains, making the training of deep-learning methods challenging. This data sparsity necessitates transfer learning strategies akin to the state-of-the-art in general computer vision. In this work, we introduce a set of methods enabling cross-domain and cross-dimension learning for image-to-graph transformers. We propose (1) a regularized edge sampling loss to effectively learn object relations in multiple domains with different numbers of edges, (2) a domain adaptation framework for image-to-graph transformers aligning image- and graph-level features from different domains, and (3) a projection function that allows using 2D data for training 3D transformers. We demonstrate our method’s utility in cross-domain and cross-dimension experiments, where we utilize labeled data from 2D road networks for simultaneous learning in vastly different target domains. Our method consistently outperforms standard transfer learning and self-supervised pretraining on challenging benchmarks, such as retinal or whole-brain vessel graph extraction.

Normative representation learning focuses on understanding the typical anatomical distributions from large datasets of medical scans from healthy individuals. Generative Artificial Intelligence (AI) leverages this attribute to synthesize images that accurately reflect these normative patterns. This capability enables the AI allowing them to effectively detect and correct anomalies in new, unseen pathological data without the need for expert labeling. Traditional anomaly detection methods often evaluate the anomaly detection performance, overlooking the crucial role of normative learning. In our analysis, we introduce novel metrics, specifically designed to evaluate this facet in AI models. We apply these metrics across various generative AI frameworks, including advanced diffusion models, and rigorously test them against complex and diverse brain pathologies. In addition, we conduct a large multi-reader study to compare these metrics to experts’ evaluations. Our analysis demonstrates that models proficient in normative learning exhibit exceptional versatility, adeptly detecting a wide range of unseen medical conditions.

The success of foundation models in natural language processing and computer vision has motivated similar approaches for general time series analysis. While these models are effective for a variety of tasks, their applicability in medical domains with limited data remains largely unexplored. To address this, we investigate the effectiveness of foundation models in medical time series analysis involving electroencephalography (EEG). Through extensive experiments on tasks such as age prediction, seizure detection, and the classification of clinically relevant EEG events, we compare their diagnostic accuracy with that of specialised EEG models. Our analysis shows that foundation models extract meaningful EEG features, outperform specialised models even without domain adaptation, and localise task-specific biomarkers. Moreover, we demonstrate that diagnostic accuracy is substantially influenced by architectural choices such as context length. Overall, our study reveals that foundation models with general time series understanding eliminate the dependency on large domain-specific datasets, making them valuable tools for clinical practice.

Dark-field radiography of the human chest has been demonstrated to have promising potential for the analysis of the lung microstructure and the diagnosis of respiratory diseases. However, previous studies of dark-field chest radiographs evaluated the lung signal only in the inspiratory breathing state. Our work aims to add a new perspective to these previous assessments by locally comparing dark-field lung information between different respiratory states. To this end, we discuss suitable image registration methods for dark-field chest radiographs to enable consistent spatial alignment of the lung in distinct breathing states. Utilizing full inspiration and expiration scans from a clinical chronic obstructive pulmonary disease study, we assess the performance of the proposed registration framework and outline applicable evaluation approaches. Our regional characterization of lung dark-field signal changes between the breathing states provides a proof-of-principle that dynamic radiography-based lung function assessment approaches may benefit from considering registered dark-field images in addition to standard plain chest radiographs.

Glioblastoma, a highly aggressive brain tumor, poses major challenges due to its poor prognosis and high morbidity rates. Partial differential equation-based models offer promising potential to enhance therapeutic outcomes by simulating patient-specific tumor behavior for improved radiotherapy planning. However, model calibration remains a bottleneck due to the high computational demands of optimization methods like Monte Carlo sampling and evolutionary algorithms. To address this, we recently introduced an approach leveraging a neural forward solver with gradient-based optimization to significantly reduce calibration time. This approach requires a highly accurate and fully differentiable forward model. We investigate multiple architectures, including (i) an enhanced TumorSurrogate, (ii) a modified nnU-Net, and (iii) a 3D Vision Transformer (ViT). The optimized TumorSurrogate achieved the best overall results, excelling in both tumor outline matching and voxel-level prediction of tumor cell concentration. It halved the MSE relative to the baseline model and achieved the highest Dice score across all tumor cell concentration thresholds. Our study demonstrates significant enhancement in forward solver performance and outlines important future research directions.

Predicting future brain states is crucial for understanding healthy aging and neurodegenerative diseases. Longitudinal brain MRI registration, a cornerstone for such analyses, has long been limited by its inability to forecast future developments, reliance on extensive, dense longitudinal data, and the need to balance registration accuracy with temporal smoothness. In this work, we present emph{TimeFlow}, a novel framework for longitudinal brain MRI registration that overcomes all these challenges. Leveraging a U-Net architecture with temporal conditioning inspired by diffusion models, TimeFlow enables accurate longitudinal registration and facilitates prospective analyses through future image prediction. Unlike traditional methods that depend on explicit smoothness regularizers and dense sequential data, TimeFlow achieves temporal consistency and continuity without these constraints. Experimental results highlight its superior performance in both future timepoint prediction and registration accuracy compared to state-of-the-art methods. Additionally, TimeFlow supports novel biological brain aging analyses, effectively differentiating neurodegenerative conditions from healthy aging. It eliminates the need for segmentation, thereby avoiding the challenges of non-trivial annotation and inconsistent segmentation errors. TimeFlow paves the way for accurate, data-efficient, and annotation-free prospective analyses of brain aging and chronic diseases.

Image registration is fundamental in medical imaging applications, such as disease progression analysis or radiation therapy planning. The primary objective of image registration is to precisely capture the deformation between two or more images, typically achieved by minimizing an optimization problem. Due to its inherent ill-posedness, regularization is a key component in driving the solution toward anatomically meaningful deformations. A wide range of regularization methods has been proposed for both conventional and deep learning-based registration. However, the appropriate application of regularization techniques often depends on the specific registration problem, and no one-fits-all method exists. Despite its importance, regularization is often overlooked or addressed with default approaches, assuming existing methods are sufficient. A comprehensive and structured review remains missing. This review addresses this gap by introducing a novel taxonomy that systematically categorizes the diverse range of proposed regularization methods. It highlights the emerging field of learned regularization, which leverages data-driven techniques to automatically derive deformation properties from the data. Moreover, this review examines the transfer of regularization methods from conventional to learning-based registration, identifies open challenges, and outlines future research directions. By emphasizing the critical role of regularization in image registration, we hope to inspire the research community to reconsider regularization strategies in modern registration algorithms and to explore this rapidly evolving field further.

Biophysical modeling of brain tumors has emerged as a promising strategy for personalizing radiotherapy planning by estimating the otherwise hidden distribution of tumor cells within the brain. However, many existing state-of-the-art methods are computationally intensive, limiting their widespread translation into clinical practice. In this work, we propose an efficient and direct method that utilizes soft physical constraints to estimate the tumor cell concentration from preoperative MRI of brain tumor patients. Our approach optimizes a 3D tumor concentration field by simultaneously minimizing the difference between the observed MRI and a physically informed loss function. Compared to existing state-of-the-art techniques, our method significantly improves predicting tumor recurrence on two public datasets with a total of 192 patients while maintaining a clinically viable runtime of under one minute - a substantial reduction from the 30 minutes required by the current best approach. Furthermore, we showcase the generalizability of our framework by incorporating additional imaging information and physical constraints, highlighting its potential to translate to various medical diffusion phenomena with imperfect data.

Feature attribution methods attempt to explain neural network predictions by identifying relevant features. However, establishing a cohesive framework for assessing feature attribution remains a challenge. There are several views through which we can evaluate attributions. One principal lens is to observe the effect of perturbing attributed features on the model’s behavior (i.e., faithfulness). While providing useful insights, existing faithfulness evaluations suffer from shortcomings that we reveal in this paper. In this work, we propose two new perspectives within the faithfulness paradigm that reveal intuitive properties: soundness and completeness. Soundness assesses the degree to which attributed features are truly predictive features, while completeness examines how well the resulting attribution reveals all the predictive features. The two perspectives are based on a firm mathematical foundation and provide quantitative metrics that are computable through efficient algorithms. We apply these metrics to mainstream attribution methods, offering a novel lens through which to analyze and compare feature attribution methods.

Employing pre-trained Large Language Models (LLMs) has become the de facto standard in Natural Language Processing (NLP) despite their extensive data requirements. Motivated by the recent surge in research focused on training LLMs with limited data, particularly in low-resource domains and languages, this paper surveys recent transfer learning approaches to optimize model performance in downstream tasks where data is scarce. We first address initial and continued pre-training strategies to better leverage prior knowledge in unseen domains and languages. We then examine how to maximize the utility of limited data during fine-tuning and few-shot learning. The final section takes a task-specific perspective, reviewing models and methods suited for different levels of data scarcity. Our goal is to provide practitioners with practical guidelines for overcoming the challenges posed by constrained data while also highlighting promising directions for future research.

Federated learning enhanced with Differential Privacy (DP) is a powerful privacy-preserving strategy to protect individuals sharing their sensitive data for processing in fields such as medicine and healthcare. Many medical applications, for example magnetic resonance imaging (MRI), rely on complex-valued signal processing techniques for data acquisition and analysis. However, the appropriate application of DP to complex-valued data is still underexplored. To address this issue, from the theoretical side, we introduce the complex-valued Gaussian mechanism, whose behaviour we characterise in terms of f-DP, -DP and Rényi-DP. Moreover, we generalise the fundamental algorithm DP stochastic gradient descent to complex-valued neural networks and present novel complex-valued neural network primitives compatible with DP. Experimentally, we showcase a proof-of-concept by training federated complex-valued neural networks with DP on a real-world task (MRI pulse sequence classification in k-space), yielding excellent utility and privacy. Our results highlight the relevance of combining federated learning with robust privacy-preserving techniques in the MRI context.

Image-to-graph transformers can effectively encode image information in graphs but are typically difficult to train and require large annotated datasets. Contrastive learning can increase data efficiency by enhancing feature representations, but existing methods are not applicable to graph labels because they operate on categorical label spaces. In this work, we propose a method enabling supervised contrastive learning for image-to-graph transformers. We introduce two supervised contrastive loss formulations based on graph similarity between label pairs that we approximate using a graph neural network. Our approach avoids tailored data augmentation techniques and can be easily integrated into existing training pipelines. We perform multiple empirical studies showcasing performance improvements across various metrics.

Interpretability, particularly in terms of human understandable concepts, is essential for building trust in machine learning models for disease classification. However, state-of-the-art image classifiers exhibit limited interpretability, posing a significant barrier to their acceptance in clinical practice. To address this, our work introduces two graph representations of the retinal vasculature, aiming to bridge the gap between high-performance classifiers and human-understandable interpretability concepts in ophthalmology. We use these graphs with the aim of training graph neural networks (GNNs) for disease staging. First, we formally and experimentally show that GNNs can learn known clinical biomarkers. In that, we show that GNNs can learn human interpretable concepts. Next, we train GNNs for disease staging and study how different aggregation strategies lead the GNN to learn more and less human interpretable features. Finally, we propose a visualization for integrated gradients on graphs, which allows us to identify if GNN models have learned human-understandable representations of the data.

Topological accuracy in medical image segmentation is a highly important property for downstream applications such as network analysis and flow modeling in vessels or cell counting. Recently, significant methodological advancements have brought well-founded concepts from algebraic topology to binary segmentation. However, these approaches have been underexplored in multi-class segmentation scenarios, where topological errors are common. We propose a general loss function for topologically faithful multi-class segmentation extending the recent Betti matching concept, which is based on induced matchings of persistence barcodes. We project the N-class segmentation problem to N single-class segmentation tasks, which allows us to use 1-parameter persistent homology, making training of neural networks computationally feasible. We validate our method on a comprehensive set of four medical datasets with highly variant topological characteristics. Our loss formulation significantly enhances topological correctness in cardiac, cell, artery-vein, and Circle of Willis segmentation.

VoxelMorph, proposed in 2018, utilizes Convolutional Neural Networks (CNNs) to address medical image registration problems. In 2021 TransMorph advanced this approach by replacing CNNs with Attention mechanisms, claiming enhanced performance. More recently, the rise of Mamba with selective state space models has led to MambaMorph, which substituted Attention with Mamba blocks, asserting superior registration. These developments prompt a critical question: does chasing the latest computational trends with “more advanced” computational blocks genuinely enhance registration accuracy, or is it merely hype? Furthermore, the role of classic high-level registration-specific designs, such as coarse-to-fine pyramid mechanism, correlation calculation, and iterative optimization, warrants scrutiny, particularly in differentiating their influence from the aforementioned low-level computational blocks. In this study, we critically examine these questions through a rigorous evaluation in brain MRI registration. We employed modularized components for each block and ensured unbiased comparisons across all methods and designs to disentangle their effects on performance. Our findings indicate that adopting “advanced” computational elements fails to significantly improve registration accuracy. Instead, well-established registration-specific designs offer fair improvements, enhancing results by a marginal 1.5% over the baseline. Our findings emphasize the importance of rigorous, unbiased evaluation and contribution disentanglement of all low- and high-level registration components, rather than simply following the computer vision trends with “more advanced” computational blocks. We advocate for simpler yet effective solutions and novel evaluation metrics that go beyond conventional registration accuracy, warranting further research across various organs and modalities.

General vision encoders like DINOv2 and SAM have recently transformed computer vision. Even though they are trained on natural images, such encoder models have excelled in medical imaging, e.g., in classification, segmentation, and registration. However, no in-depth comparison of different state-of-the-art general vision encoders for medical registration is available. In this work, we investigate how well general vision encoder features can be used in the dissimilarity metrics for medical image registration. We explore two encoders that were trained on natural images as well as one that was fine-tuned on medical data. We apply the features within the well-established B-spline FFD registration framework. In extensive experiments on cardiac cine MRI data, we find that using features as additional guidance for conventional metrics improves the registration quality.

Report generation models offer fine-grained textual interpretations of medical images like chest X-rays, yet they often lack interactivity (i.e. the ability to steer the generation process through user queries) and localized interpretability (i.e. visually grounding their predictions), which we deem essential for future adoption in clinical practice. While there have been efforts to tackle these issues, they are either limited in their interactivity by not supporting textual queries or fail to also offer localized interpretability. Therefore, we propose a novel multitask architecture and training paradigm integrating textual prompts and bounding boxes for diverse aspects like anatomical regions and pathologies. We call this approach the Chest X-Ray Explainer (ChEX). Evaluations across a heterogeneous set of 9 chest X-ray tasks, including localized image interpretation and report generation, showcase its competitiveness with SOTA models while additional analysis demonstrates ChEX’s interactive capabilities.

The rapid development of artificial intelligence (AI) has gained importance, with many tools already entering our daily lives. The medical field of radiation oncology is also subject to this development, with AI entering all steps of the patient journey. In this review article, we summarize contemporary AI techniques and explore the clinical applications of AI-based automated segmentation models in radiotherapy planning, focusing on delineation of organs at risk (OARs), the gross tumor volume (GTV), and the clinical target volume (CTV). Emphasizing the need for precise and individualized plans, we review various commercial and freeware segmentation tools and also state-of-the-art approaches. Through our own findings and based on the literature, we demonstrate improved efficiency and consistency as well as time savings in different clinical scenarios. Despite challenges in clinical implementation such as domain shifts, the potential benefits for personalized treatment planning are substantial. The integration of mathematical tumor growth models and AI-based tumor detection further enhances the possibilities for refining target volumes. As advancements continue, the prospect of one-stop-shop segmentation and radiotherapy planning represents an exciting frontier in radiotherapy, potentially enabling fast treatment with enhanced precision and individualization.

Cardiac magnetic resonance (CMR) image acquisition requires subjects to hold their breath while 2D cine images are acquired. This process assumes that the heart remains in the same position across all slices. However, differences in breathhold positions or patient motion introduce 3D slice misalignments. In this work, we propose an algorithm that simultaneously aligns all SA and LA slices by maximizing the pair-wise intensity agreement between their intersections. Unlike previous works, our approach is formulated as a subject-specific optimization problem and requires no prior knowledge of the underlying anatomy. We quantitatively demonstrate that the proposed method is robust against a large range of rotations and translations by synthetically misaligning 10 motion-free datasets and aligning them back using the proposed method.

The prevailing deep learning-based methods of predicting cardiac segmentation involve reconstructed magnetic resonance (MR) images. The heavy dependency of segmentation approaches on image quality significantly limits the acceleration rate in fast MR reconstruction. Moreover, the practice of treating reconstruction and segmentation as separate sequential processes leads to artifact generation and information loss in the intermediate stage. These issues pose a great risk to achieving high-quality outcomes. To leverage the redundant k-space information overlooked in this dual-step pipeline, we introduce a novel approach to directly deriving segmentations from sparse k-space samples using a transformer (DiSK). DiSK operates by globally extracting latent features from 2D+time k-space data with attention blocks and subsequently predicting the segmentation label of query points. We evaluate our model under various acceleration factors (ranging from 4 to 64) and compare against two image-based segmentation baselines. Our model consistently outperforms the baselines in Dice and Hausdorff distances across foreground classes for all presented sampling rates.

Feature attribution explains neural network outputs by identifying relevant input features. How do we know if the identified features are indeed relevant to the network? This notion is referred to as faithfulness, an essential property that reflects the alignment between the identified (attributed) features and the features used by the model. One recent trend to test faithfulness is to design the data such that we know which input features are relevant to the label and then train a model on the designed data. Subsequently, the identified features are evaluated by comparing them with these designed ground truth features. However, this idea has the underlying assumption that the neural network learns to use all and only these designed features, while there is no guarantee that the learning process trains the network in this way. In this paper, we solve this missing link by explicitly designing the neural network by manually setting its weights, along with designing data, so we know precisely which input features in the dataset are relevant to the designed network. Thus, we can test faithfulness in AttributionLab, our designed synthetic environment, which serves as a sanity check and is effective in filtering out attribution methods. If an attribution method is not faithful in a simple controlled environment, it can be unreliable in more complex scenarios. Furthermore, the AttributionLab environment serves as a laboratory for controlled experiments through which we can study feature attribution methods, identify issues, and suggest potential improvements.

Segmentation of anatomical shapes from medical images has taken an important role in the automation of clinical measurements. While typical deep-learning segmentation approaches are performed on discrete voxels, the underlying objects being analysed exist in a real-valued continuous space. Approaches that rely on convolutional neural networks (CNNs) are limited to grid-like inputs and not easily applicable to sparse or partial measurements. We propose a novel family of image segmentation models that tackle many of CNNs’ shortcomings: Neural Implicit Segmentation Functions (NISF). Our framework takes inspiration from the field of neural implicit functions where a network learns a mapping from a real-valued coordinate-space to a shape representation. NISFs have the ability to segment anatomical shapes in high-dimensional continuous spaces. Training is not limited to voxelized grids, and covers applications with sparse and partial data. Interpolation between observations is learnt naturally in the training procedure and requires no post-processing. Furthermore, NISFs allow the leveraging of learnt shape priors to make predictions for regions outside of the original image plane. We go on to show the framework achieves dice scores of on a (3D+t) short-axis cardiac segmentation task using the UK Biobank dataset. We also provide a qualitative analysis on our frameworks ability to perform segmentation and image interpolation on unseen regions of an image volume at arbitrary resolutions.

Feature attribution is arguably the predominant approach for illuminating black-box neural networks. This dissertation rethinks feature attribution by leveraging critical neural pathways, identifying input features with predictive information, and evaluating feature attribution using the neural network model. The dissertation also rethinks feature attribution for the explanation of medical imaging models.

Do black-box neural network models learn clinically relevant features for fracture diagnosis? The answer not only establishes reliability, quenches scientific curiosity, but also leads to explainable and verbose findings that can assist the radiologists in the final and increase trust. This work identifies the concepts networks use for vertebral fracture diagnosis in CT images. This is achieved by associating concepts to neurons highly correlated with a specific diagnosis in the dataset. The concepts are either associated with neurons by radiologists pre-hoc or are visualized during a specific prediction and left for the user’s interpretation. We evaluate which concepts lead to correct diagnosis and which concepts lead to false positives. The proposed frameworks and analysis pave the way for reliable and explainable vertebral fracture diagnosis.

One challenging property lurking in medical datasets is the imbalanced data distribution, where the frequency of the samples between the different classes is not balanced. Training a model on an imbalanced dataset can introduce unique challenges to the learning problem where a model is biased towards the highly frequent class. Many methods are proposed to tackle the distributional differences and the imbalanced problem. However, the impact of these approaches on the learned features is not well studied. In this paper, we look deeper into the internal units of neural networks to observe how handling data imbalance affects the learned features. We study several popular cost-sensitive approaches for handling data imbalance and analyze the feature maps of the convolutional neural networks from multiple perspectives: analyzing the alignment of salient features with pathologies and analyzing the pathology-related concepts encoded by the networks. Our study reveals differences and insights regarding the trained models that are not reflected by quantitative metrics such as AUROC and AP and show up only by looking at the models through a lens.

It is a mystery which input features contribute to a neural network’s output. Various explanation (feature attribution) methods are proposed in the literature to shed light on the problem. One peculiar observation is that these explanations (attributions) point to different features as being important. The phenomenon raises the question, which explanation to trust? We propose a framework for evaluating the explanations using the neural network model itself. The framework leverages the network to generate input features that impose a particular behavior on the output. Using the generated features, we devise controlled experimental setups to evaluate whether an explanation method conforms to an axiom. Thus we propose an empirical framework for axiomatic evaluation of explanation methods. We evaluate well-known and promising explanation solutions using the proposed framework. The framework provides a toolset to reveal properties and drawbacks within existing and future explanation solutions

The automation of chest X-ray reporting has garnered significant interest due to the time-consuming nature of the task. However, the clinical accuracy of free-text reports has proven challenging to quantify using natural language processing metrics, given the complexity of medical information, the variety of writing styles, and the potential for typos and inconsistencies. Structured reporting and standardized reports, on the other hand, can provide consistency and formalize the evaluation of clinical correctness. However, high-quality annotations for structured reporting are scarce. Therefore, we propose a method to predict clinical findings defined by sentences in structured reporting templates, which can be used to fill such templates. The approach involves training a contrastive language-image model using chest X-rays and related free-text radiological reports, then creating textual prompts for each structured finding and optimizing a classifier to predict clinical findings in the medical image. Results show that even with limited image-level annotations for training, the method can accomplish the structured reporting tasks of severity assessment of cardiomegaly and localizing pathologies in chest X-rays.

One principal approach for illuminating a black-box neural network is feature attribution, i.e. identifying the importance of input features for the network’s prediction. The predictive information of features is recently proposed as a proxy for the measure of their importance. So far, the predictive information is only identified for latent features by placing an information bottleneck within the network. We propose a method to identify features with predictive information in the input domain. The method results in fine-grained identification of input features’ information and is agnostic to network architecture. The core idea of our method is leveraging a bottleneck on the input that only lets input features associated with predictive latent features pass through. We compare our method with several feature attribution methods using mainstream feature attribution evaluation experiments. The code is publicly available.

Convolutional neural networks are showing promise in the automatic diagnosis of thoracic pathologies on chest x-rays. Their black-box nature has sparked many recent works to explain the prediction via input feature attribution methods (aka saliency methods). However, input feature attribution methods merely identify the importance of input regions for the prediction and lack semantic interpretation of model behavior. In this work, we first identify the semantics associated with internal units (feature maps) of the network. We proceed to investigate the following questions; Does a regression model that is only trained with COVID-19 severity scores implicitly learn visual patterns associated with thoracic pathologies? Does a network that is trained on weakly labeled data (e.g. healthy, unhealthy) implicitly learn pathologies? Moreover, we investigate the effect of pretraining and data imbalance on the interpretability of learned features. In addition to the analysis, we propose semantic attribution to semantically explain each prediction. We present our findings using publicly available chest pathologies (CheXpert [5], NIH ChestX-ray8 [25]) and COVID-19 datasets (BrixIA [20], and COVID-19 chest X-ray segmentation dataset [4]).

Neural networks have demonstrated remarkable performance in classification and regression tasks on chest X-rays. In order to establish trust in the clinical routine, the networks’ prediction mechanism needs to be interpretable. One principal approach to interpretation is feature attribution. Feature attribution methods identify the importance of input features for the output prediction. Building on Information Bottleneck Attribution (IBA) method, for each prediction we identify the chest X-ray regions that have high mutual information with the network’s output. Original IBA identifies input regions that have sufficient predictive information. We propose Inverse IBA to identify all informative regions. Thus all predictive cues for pathologies are highlighted on the X-rays, a desirable property for chest X-ray diagnosis. Moreover, we propose Regression IBA for explaining regression models. Using Regression IBA we observe that a model trained on cumulative severity score labels implicitly learns the severity of different X-ray regions. Finally, we propose Multi-layer IBA to generate higher resolution and more detailed attribution/saliency maps. We evaluate our methods using both human-centric (ground-truth-based) interpretability metrics, and human-agnostic feature importance metrics on NIH Chest X-ray8 and BrixIA datasets.

Is critical input information encoded in specific sparse pathways within the neural network? In this work, we discuss the problem of identifying these critical pathways and subsequently leverage them for interpreting the network’s response to an input. The pruning objective — selecting the smallest group of neurons for which the response remains equivalent to the original network — has been previously proposed for identifying critical pathways. We demonstrate that sparse pathways derived from pruning do not necessarily encode critical input information. To ensure sparse pathways include critical fragments of the encoded input information, we propose pathway selection via neurons’ contribution to the response. We proceed to explain how critical pathways can reveal critical input features. We prove that pathways selected via neuron contribution are locally linear (in an ℓ 2 -ball), a property that we use for proposing a feature attribution method: ‘pathway gradient’. We validate our interpretation method using mainstream evaluation experiments. The validation of pathway gradient interpretation method further confirms that selected pathways using neuron contributions correspond to critical input features. The code 1 2 is publicly available.

Segmentation of Multiple Sclerosis (MS) lesions in longitudinal brain MR scans is performed for monitoring the progression of MS lesions. We hypothesize that the spatio-temporal cues in longitudinal data can aid the segmentation algorithm. Therefore, we propose a multi-task learning approach by defining an auxiliary self-supervised task of deformable registration between two time-points to guide the neural network toward learning from spatio-temporal changes. We show the efficacy of our method on a clinical dataset comprised of 70 patients with one follow-up study for each patient. Our results show that spatio-temporal information in longitudinal data is a beneficial cue for improving segmentation. We improve the result of current state-of-the-art by 2.6% in terms of overall score (p < 0.05).