Georg Langs

Kelly Payette, Hongwei Li, Priscille de Dumast et al.

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.

Stanislav Motyka, Paul Weiser, Beata Bachrata et al.

Subject movement during the magnetic resonance examination is inevitable and causes not only image artefacts but also deteriorates the homogeneity of the main magnetic field (B0), which is a prerequisite for high quality data. Thus, characterization of changes to B0, e.g. induced by patient movement, is important for MR applications that are prone to B0 inhomogeneities. We propose a deep learning based method to predict such changes within the brain from the change of the head position to facilitate retrospective or even real-time correction. A 3D U-net was trained on in vivo brain 7T MRI data. The input consisted of B0 maps and anatomical images at an initial position, and anatomical images at a different head position (obtained by applying a rigid-body transformation on the initial anatomical image). The output consisted of B0 maps at the new head positions. We further fine-tuned the network weights to each subject by measuring a limited number of head positions of the given subject, and trained the U-net with these data. Our approach was compared to established dynamic B0 field mapping via interleaved navigators, which suffer from limited spatial resolution and the need for undesirable sequence modifications. Qualitative and quantitative comparison showed similar performance between an interleaved navigator-equivalent method and proposed method. We therefore conclude that it is feasible to predict B0 maps from rigid subject movement and, when combined with external tracking hardware, this information could be used to improve the quality of magnetic resonance acquisitions without the use of navigators.

Clemens Watzenböck, Daniel Aletaha, Michaël Deman et al.

Quantitative disease severity scoring in medical imaging is costly, time-consuming, and subject to inter-reader variability. At the same time, clinical archives contain far more longitudinal imaging data than expert-annotated severity scores. Existing self-supervised methods typically ignore this chronological structure. We introduce ChronoCon, a contrastive learning approach that replaces label-based ranking losses with rankings derived solely from the visitation order of a patient's longitudinal scans. Under the clinically plausible assumption of monotonic progression in irreversible diseases, the method learns disease-relevant representations without using any expert labels. This generalizes the idea of Rank-N-Contrast from label distances to temporal ordering. Evaluated on rheumatoid arthritis radiographs for severity assessment, the learned representations substantially improve label efficiency. In low-label settings, ChronoCon significantly outperforms a fully supervised baseline initialized from ImageNet weights. In a few-shot learning experiment, fine-tuning ChronoCon on expert scores from only five patients yields an intraclass correlation coefficient of 86% for severity score prediction. These results demonstrate the potential of chronological contrastive learning to exploit routinely available imaging metadata to reduce annotation requirements in the irreversible disease domain. Code is available at https://github.com/cirmuw/ChronoCon.

Paul Weiser, Georg Langs, Wolfgang Bogner et al.

Introduction: Altered neurometabolism is an important pathological mechanism in many neurological diseases and brain cancer, which can be mapped non-invasively by Magnetic Resonance Spectroscopic Imaging (MRSI). Advanced MRSI using non-cartesian compressed-sense acquisition enables fast high-resolution metabolic imaging but has lengthy reconstruction times that limits throughput and needs expert user interaction. Here, we present a robust and efficient Deep Learning reconstruction to obtain high-quality metabolic maps. Methods: Fast high-resolution whole-brain metabolic imaging was performed at 3.4 mm$^3$ isotropic resolution with acquisition times between 4:11-9:21 min:s using ECCENTRIC pulse sequence on a 7T MRI scanner. Data were acquired in a high-resolution phantom and 27 human participants, including 22 healthy volunteers and 5 glioma patients. A deep neural network using recurring interlaced convolutional layers with joint dual-space feature representation was developed for deep learning ECCENTRIC reconstruction (Deep-ER). 21 subjects were used for training and 6 subjects for testing. Deep-ER performance was compared to conventional iterative Total Generalized Variation reconstruction using image and spectral quality metrics. Results: Deep-ER demonstrated 600-fold faster reconstruction than conventional methods, providing improved spatial-spectral quality and metabolite quantification with 12%-45% (P<0.05) higher signal-to-noise and 8%-50% (P<0.05) smaller Cramer-Rao lower bounds. Metabolic images clearly visualize glioma tumor heterogeneity and boundary. Conclusion: Deep-ER provides efficient and robust reconstruction for sparse-sampled MRSI. The accelerated acquisition-reconstruction MRSI is compatible with high-throughput imaging workflow. It is expected that such improved performance will facilitate basic and clinical MRSI applications.

Felicia Bader, Philipp Seeböck, Anastasia Bartashova et al.

In diagnostic reports, experts encode complex imaging data into clinically actionable information. They describe subtle pathological findings that are meaningful in their anatomical context. Reports follow relatively consistent structures, expressing diagnostic information with few words that are often associated with tiny but consequential image observations. Standard vision language models struggle to identify the associations between these informative text components and small locations in the images. Here, we propose "MApLe", a multi-task, multi-instance vision language alignment approach that overcomes these limitations. It disentangles the concepts of anatomical region and diagnostic finding, and links local image information to sentences in a patch-wise approach. Our method consists of a text embedding trained to capture anatomical and diagnostic concepts in sentences, a patch-wise image encoder conditioned on anatomical structures, and a multi-instance alignment of these representations. We demonstrate that MApLe can successfully align different image regions and multiple diagnostic findings in free-text reports. We show that our model improves the alignment performance compared to state-of-the-art baseline models when evaluated on several downstream tasks. The code is available at https://github.com/cirmuw/MApLe.

Jeanny Pan, Philipp Seeböck, Christoph Fürböck et al.

Identifying new disease-related patterns in medical imaging data with the help of machine learning enlarges the vocabulary of recognizable findings. This supports diagnostic and prognostic assessment. However, image appearance varies not only due to biological differences, but also due to imaging technology linked to vendors, scanning- or re- construction parameters. The resulting domain shifts impedes data representation learning strategies and the discovery of biologically meaningful cluster appearances. To address these challenges, we introduce an approach to actively learn the domain shift via post-hoc rotation of the data latent space, enabling disentanglement of biological and technical factors. Results on real-world heterogeneous clinical data showcase that the learned disentangled representation leads to stable clusters representing tissue-types across different acquisition settings. Cluster consistency is improved by +19.01% (ARI), +16.85% (NMI), and +12.39% (Dice) compared to the entangled representation, outperforming four state-of-the-art harmonization methods. When using the clusters to quantify tissue composition on idiopathic pulmonary fibrosis patients, the learned profiles enhance Cox survival prediction. This indicates that the proposed label-free framework facilitates biomarker discovery in multi-center routine imaging data. Code is available on GitHub https://github.com/cirmuw/latent-space-rotation-disentanglement.

Johannes Tischer, Patric Kienast, Marlene Stümpflen et al.

Magnetic Resonance Imaging (MRI) of the fetal brain has become a key tool for studying brain development in vivo. Yet, its assessment remains challenging due to variability in brain maturation, imaging protocols, and uncertain estimates of Gestational Age (GA). To overcome these, brain atlases provide a standardized reference framework that facilitates objective evaluation and comparison across subjects by aligning the atlas and subjects in a common coordinate system. In this work, we introduce a novel deep-learning framework for generating continuous, age-specific fetal brain atlases for real-time fetal brain tissue segmentation. The framework combines a direct registration model with a conditional discriminator. Trained on a curated dataset of 219 neurotypical fetal MRIs spanning from 21 to 37 weeks of gestation. The method achieves high registration accuracy, captures dynamic anatomical changes with sharp structural detail, and robust segmentation performance with an average Dice Similarity Coefficient (DSC) of 86.3% across six brain tissues. Furthermore, volumetric analysis of the generated atlases reveals detailed neurotypical growth trajectories, providing valuable insights into the maturation of the fetal brain. This approach enables individualized developmental assessment with minimal pre-processing and real-time performance, supporting both research and clinical applications. The model code is available at https://github.com/cirmuw/fetal-brain-atlas

Mohammed Kamran, Maria Bernathova, Raoul Varga et al.

Accurate segmentation of small lesions in Breast Dynamic Contrast-Enhanced MRI (DCE-MRI) is critical for early cancer detection, especially in high-risk patients. While recent deep learning methods have advanced lesion segmentation, they primarily target large lesions and neglect valuable longitudinal and clinical information routinely used by radiologists. In real-world screening, detecting subtle or emerging lesions requires radiologists to compare across timepoints and consider previous radiology assessments, such as the BI-RADS score. We propose LesiOnTime, a novel 3D segmentation approach that mimics clinical diagnostic workflows by jointly leveraging longitudinal imaging and BIRADS scores. The key components are: (1) a Temporal Prior Attention (TPA) block that dynamically integrates information from previous and current scans; and (2) a BI-RADS Consistency Regularization (BCR) loss that enforces latent space alignment for scans with similar radiological assessments, thus embedding domain knowledge into the training process. Evaluated on a curated in-house longitudinal dataset of high-risk patients with DCE-MRI, our approach outperforms state-of-the-art single-timepoint and longitudinal baselines by 5% in terms of Dice. Ablation studies demonstrate that both TPA and BCR contribute complementary performance gains. These results highlight the importance of incorporating temporal and clinical context for reliable early lesion segmentation in real-world breast cancer screening. Our code is publicly available at https://github.com/cirmuw/LesiOnTime

Murong Xu, Tamaz Amiranashvili, Fernando Navarro et al.

Accurate delineation of anatomical structures in volumetric CT scans is crucial for diagnosis and treatment planning. While AI has advanced automated segmentation, current approaches typically target individual structures, creating a fragmented landscape of incompatible models with varying performance and disparate evaluation protocols. Foundational segmentation models address these limitations by providing a holistic anatomical view through a single model. Yet, robust clinical deployment demands comprehensive training data, which is lacking in existing whole-body approaches, both in terms of data heterogeneity and, more importantly, anatomical coverage. In this work, rather than pursuing incremental optimizations in model architecture, we present CADS, an open-source framework that prioritizes the systematic integration, standardization, and labeling of heterogeneous data sources for whole-body CT segmentation. At its core is a large-scale dataset of 22,022 CT volumes with complete annotations for 167 anatomical structures, representing a significant advancement in both scale and coverage, with 18 times more scans than existing collections and 60% more distinct anatomical targets. Building on this diverse dataset, we develop the CADS-model using established architectures for accessible and automated full-body CT segmentation. Through comprehensive evaluation across 18 public datasets and an independent real-world hospital cohort, we demonstrate advantages over SoTA approaches. Notably, thorough testing of the model's performance in segmentation tasks from radiation oncology validates its direct utility for clinical interventions. By making our large-scale dataset, our segmentation models, and our clinical software tool publicly available, we aim to advance robust AI solutions in radiology and make comprehensive anatomical analysis accessible to clinicians and researchers alike.

Ajay Mittal, Raghav Mehta, Omar Todd et al.

Automatic detection and classification of Cardiovascular disease (CVD) from Computed Tomography (CT) images play an important part in facilitating better-informed clinical decisions. However, most of the recent deep learning based methods either directly work on raw CT data or utilize it in pair with anatomical cardiac structure segmentation by training an end-to-end classifier. As such, these approaches become much more difficult to interpret from a clinical perspective. To address this challenge, in this work, we break down the CVD classification pipeline into three components: (i) image segmentation, (ii) image registration, and (iii) downstream CVD classification. Specifically, we utilize the Atlas-ISTN framework and recent segmentation foundational models to generate anatomical structure segmentation and a normative healthy atlas. These are further utilized to extract clinically interpretable radiomic features as well as deformation field based geometric features (through atlas registration) for CVD classification. Our experiments on the publicly available ASOCA dataset show that utilizing these features leads to better CVD classification accuracy (87.50\%) when compared against classification model trained directly on raw CT images (67.50\%). Our code is publicly available: https://github.com/biomedia-mira/grc-net

Daniel Sobotka, Michael Ebner, Ernst Schwartz et al.

Motion correction is an essential preprocessing step in functional Magnetic Resonance Imaging (fMRI) of the fetal brain with the aim to remove artifacts caused by fetal movement and maternal breathing and consequently to suppress erroneous signal correlations. Current motion correction approaches for fetal fMRI choose a single 3D volume from a specific acquisition timepoint with least motion artefacts as reference volume, and perform interpolation for the reconstruction of the motion corrected time series. The results can suffer, if no low-motion frame is available, and if reconstruction does not exploit any assumptions about the continuity of the fMRI signal. Here, we propose a novel framework, which estimates a high-resolution reference volume by using outlier-robust motion correction, and by utilizing Huber L2 regularization for intra-stack volumetric reconstruction of the motion-corrected fetal brain fMRI. We performed an extensive parameter study to investigate the effectiveness of motion estimation and present in this work benchmark metrics to quantify the effect of motion correction and regularised volumetric reconstruction approaches on functional connectivity computations. We demonstrate the proposed framework's ability to improve functional connectivity estimates, reproducibility and signal interpretability, which is clinically highly desirable for the establishment of prognostic noninvasive imaging biomarkers. The motion correction and volumetric reconstruction framework is made available as an open-source package of NiftyMIC.

Lucas Fidon, Michael Aertsen, Thomas Deprest et al.

Limiting failures of machine learning systems is of paramount importance for safety-critical applications. In order to improve the robustness of machine learning systems, Distributionally Robust Optimization (DRO) has been proposed as a generalization of Empirical Risk Minimization (ERM). However, its use in deep learning has been severely restricted due to the relative inefficiency of the optimizers available for DRO in comparison to the wide-spread variants of Stochastic Gradient Descent (SGD) optimizers for ERM. We propose SGD with hardness weighted sampling, a principled and efficient optimization method for DRO in machine learning that is particularly suited in the context of deep learning. Similar to a hard example mining strategy in practice, the proposed algorithm is straightforward to implement and computationally as efficient as SGD-based optimizers used for deep learning, requiring minimal overhead computation. In contrast to typical ad hoc hard mining approaches, we prove the convergence of our DRO algorithm for over-parameterized deep learning networks with ReLU activation and a finite number of layers and parameters. Our experiments on fetal brain 3D MRI segmentation and brain tumor segmentation in MRI demonstrate the feasibility and the usefulness of our approach. Using our hardness weighted sampling for training a state-of-the-art deep learning pipeline leads to improved robustness to anatomical variabilities in automatic fetal brain 3D MRI segmentation using deep learning and to improved robustness to the image protocol variations in brain tumor segmentation. Our code is available at https://github.com/LucasFidon/HardnessWeightedSampler.

Daniel Sobotka, Alexander Herold, Matthias Perkonigg et al.

Liver vessel segmentation in magnetic resonance imaging data is important for the computational analysis of vascular remodelling, associated with a wide spectrum of diffuse liver diseases. Existing approaches rely on contrast enhanced imaging data, but the necessary dedicated imaging sequences are not uniformly acquired. Images without contrast enhancement are acquired more frequently, but vessel segmentation is challenging, and requires large-scale annotated data. We propose a multi-task learning framework to segment vessels in liver MRI without contrast. It exploits auxiliary contrast enhanced MRI data available only during training to reduce the need for annotated training examples. Our approach draws on paired native and contrast enhanced data with and without vessel annotations for model training. Results show that auxiliary data improves the accuracy of vessel segmentation, even if they are not available during inference. The advantage is most pronounced if only few annotations are available for training, since the feature representation benefits from the shared task structure. A validation of this approach to augment a model for brain tumor segmentation confirms its benefits across different domains. An auxiliary informative imaging modality can augment expert annotations even if it is only available during training.

Vladyslav Zalevskyi, Thomas Sanchez, Margaux Roulet et al.

Fetal brain tissue segmentation in magnetic resonance imaging (MRI) is a crucial tool that supports understanding of neurodevelopment, yet it faces challenges due to the heterogeneity of data coming from different scanners and settings, as well as data scarcity. Recent approaches based on domain randomization, like SynthSeg, have shown great potential for single-source domain generalization by simulating images with randomized contrast and image resolution from the label maps. In this work, we investigate how to maximize the out-of-domain (OOD) generalization potential of SynthSegbased methods in fetal brain MRI. Specifically, we demonstrate that the simple Gaussian mixture models employed in FetalSynthSeg outperform physics-informed generation methods in terms of OOD generalization. We further show that incorporating intensity clustering significantly enhances generalization in settings with limited label classes by producing more realistic synthetic data. By combining synthetic pretraining with fine-tuning on real images and applying weight-space interpolation between the two models, we propose DRIFTS as an effective and practical solution for single-source domain generalization. DRIFTS consistently outperforms current state-of-the-art models across multiple benchmarks and is, to our knowledge, the first method to achieve accurate brain tissue segmentation on fetal T1-weighted images. We validate our approach on 308 subjects from four datasets acquired at three different sites, covering a range of scanner field strengths (0.55T to 3T) and both T1w and T2w modalities. We conclude with five practical recommendations to guide the development of SynthSeg-based methods for other organs and imaging modalities.

Paul J. Weiser, Gulnur Ungan, Amirmohammad Shamaei et al.

Purpose: Proton magnetic resonance spectroscopic imaging ($^1$H MRSI) enables the mapping of whole-brain metabolites concentrations in-vivo. However, a long-standing problem for its clinical applicability is the metabolic quantification, which can require extensive time for spectral fitting. Recently, deep learning methods have been able to provide whole-brain metabolic quantification in only a few seconds. However, neural network implementations often lack configurability and require retraining to change predefined parameter settings. Methods: We introduce HyperFitS, a hypernetwork for spectral fitting for metabolite quantification in whole-brain $^1$H MRSI that flexibly adapts to a broad range of baseline corrections and water suppression factors. Metabolite maps of human subjects acquired at 3T and 7T with isotropic resolutions of 10 mm, 3.4 mm and 2 mm by water-suppressed and water-unsuppressed MRSI were quantified with HyperFitS and compared to conventional LCModel fitting. Results: Metabolic maps show a substantial agreement between the new and gold-standard methods, with significantly faster fitting times by HyperFitS. Quantitative results further highlight the impact of baseline parametrization on metabolic quantification, which can alter results by up to 30%. Conclusion: HyperFitS shows strong agreement with state-of-the-art conventional methods, while reducing processing times from hours to a few seconds. Compared to prior deep learning based spectral fitting methods, HyperFitS enables a wide range of configurability and can adapt to data quality acquired with multiple protocols and field strengths without retraining.

Ziyao Shang, Misha Kaandorp, Kelly Payette et al.

Magnetic resonance imaging (MRI) has played a crucial role in fetal neurodevelopmental research. Structural annotations of MR images are an important step for quantitative analysis of the developing human brain, with Deep learning providing an automated alternative for this otherwise tedious manual process. However, segmentation performances of Convolutional Neural Networks often suffer from domain shift, where the network fails when applied to subjects that deviate from the distribution with which it is trained on. In this work, we aim to train networks capable of automatically segmenting fetal brain MRIs with a wide range of domain shifts pertaining to differences in subject physiology and acquisition environments, in particular shape-based differences commonly observed in pathological cases. We introduce a novel data-driven train-time sampling strategy that seeks to fully exploit the diversity of a given training dataset to enhance the domain generalizability of the trained networks. We adapted our sampler, together with other existing data augmentation techniques, to the SynthSeg framework, a generator that utilizes domain randomization to generate diverse training data, and ran thorough experimentations and ablation studies on a wide range of training/testing data to test the validity of the approaches. Our networks achieved notable improvements in the segmentation quality on testing subjects with intense anatomical abnormalities (p < 1e-4), though at the cost of a slighter decrease in performance in cases with fewer abnormalities. Our work also lays the foundation for future works on creating and adapting data-driven sampling strategies for other training pipelines.

Stefan Brandstätter, Philipp Seeböck, Christoph Fürböck et al.

2D to 3D registration is essential in tasks such as diagnosis, surgical navigation, environmental understanding, navigation in robotics, autonomous systems, or augmented reality. In medical imaging, the aim is often to place a 2D image in a 3D volumetric observation to w. Current approaches for rigid single slice in volume registration are limited by requirements such as pose initialization, stacks of adjacent slices, or reliable anatomical landmarks. Here, we propose a self-supervised 2D/3D registration approach to match a single 2D slice to the corresponding 3D volume. The method works in data without anatomical priors such as images of tumors. It addresses the dimensionality disparity and establishes correspondences between 2D in-plane and 3D out-of-plane rotation-equivariant features by using group equivariant CNNs. These rotation-equivariant features are extracted from the 2D query slice and aligned with their 3D counterparts. Results demonstrate the robustness of the proposed slice-in-volume registration on the NSCLC-Radiomics CT and KIRBY21 MRI datasets, attaining an absolute median angle error of less than 2 degrees and a mean-matching feature accuracy of 89% at a tolerance of 3 pixels.

Alexander Herold, Daniel Sobotka, Lucian Beer et al.

Background: We aimed to quantify hepatic vessel volumes across chronic liver disease stages and healthy controls using deep learning-based magnetic resonance imaging (MRI) analysis, and assess correlations with biomarkers for liver (dys)function and fibrosis/portal hypertension. Methods: We assessed retrospectively healthy controls, non-advanced and advanced chronic liver disease (ACLD) patients using a 3D U-Net model for hepatic vessel segmentation on portal venous phase gadoxetic acid-enhanced 3-T MRI. Total (TVVR), hepatic (HVVR), and intrahepatic portal vein-to-volume ratios (PVVR) were compared between groups and correlated with: albumin-bilirubin (ALBI) and model for end-stage liver disease-sodium (MELD-Na) score, and fibrosis/portal hypertension (Fibrosis-4 [FIB-4] score, liver stiffness measurement [LSM], hepatic venous pressure gradient [HVPG], platelet count [PLT], and spleen volume). Results: We included 197 subjects, aged 54.9 $\pm$ 13.8 years (mean $\pm$ standard deviation), 111 males (56.3\%): 35 healthy controls, 44 non-ACLD, and 118 ACLD patients. TVVR and HVVR were highest in controls (3.9; 2.1), intermediate in non-ACLD (2.8; 1.7), and lowest in ACLD patients (2.3; 1.0) ($p \leq 0.001$). PVVR was reduced in both non-ACLD and ACLD patients (both 1.2) compared to controls (1.7) ($p \leq 0.001$), but showed no difference between CLD groups ($p = 0.999$). HVVR significantly correlated indirectly with FIB-4, ALBI, MELD-Na, LSM, and spleen volume ($ρ$ ranging from -0.27 to -0.40), and directly with PLT ($ρ= 0.36$). TVVR and PVVR showed similar but weaker correlations. Conclusions: Deep learning-based hepatic vessel volumetry demonstrated differences between healthy liver and chronic liver disease stages and shows correlations with established markers of disease severity.

Ivana Janíčková, Yen Y. Tan, Thomas H. Helbich et al.

Effective therapy decisions require models that predict the individual response to treatment. This is challenging since the progression of disease and response to treatment vary substantially across patients. Here, we propose to learn a representation of the early dynamics of treatment response from imaging data to predict pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). The longitudinal change in magnetic resonance imaging (MRI) data of the breast forms trajectories in the latent space, serving as basis for prediction of successful response. The multi-task model represents appearance, fosters temporal continuity and accounts for the comparably high heterogeneity in the non-responder cohort.In experiments on the publicly available ISPY-2 dataset, a linear classifier in the latent trajectory space achieves a balanced accuracy of 0.761 using only pre-treatment data (T0), 0.811 using early response (T0 + T1), and 0.861 using four imaging time points (T0 -> T3). The code will be made available upon paper acceptance.

Branko Mitic, Philipp Seeböck, Helmut Prosch et al.

Early detection of newly emerging diseases, lesion severity assessment, differentiation of medical conditions and automated screening are examples for the wide applicability and importance of anomaly detection (AD) and unsupervised segmentation in medicine. Normal fine-grained tissue variability such as present in pulmonary anatomy is a major challenge for existing generative AD methods. Here, we propose a novel generative AD approach addressing this issue. It consists of an image-to-image translation for anomaly-free reconstruction and a subsequent patch similarity scoring between observed and generated image-pairs for precise anomaly localization. We validate the new method on chest computed tomography (CT) scans for the detection and segmentation of infectious disease lesions. To assess generalizability, we evaluate the method on an ischemic stroke lesion segmentation task in T1-weighted brain MRI. Results show improved pixel-level anomaly segmentation in both chest CTs and brain MRIs, with relative DICE score improvements of +1.9% and +4.4%, respectively, compared to other state-of-the-art reconstruction-based methods.

Christoph Fürböck, Paul Weiser, Branko Mitic et al.

In real world clinical environments, training and applying deep learning models on multi-modal medical imaging data often struggles with partially incomplete data. Standard approaches either discard missing samples, require imputation or repurpose dropout learning schemes, limiting robustness and generalizability. To address this, we propose a hypernetwork-based method that dynamically generates task-specific classification models conditioned on the set of available modalities. Instead of training a fixed model, a hypernetwork learns to predict the parameters of a task model adapted to available modalities, enabling training and inference on all samples, regardless of completeness. We compare this approach with (1) models trained only on complete data, (2) state of the art channel dropout methods, and (3) an imputation-based method, using artificially incomplete datasets to systematically analyze robustness to missing modalities. Results demonstrate superior adaptability of our method, outperforming state of the art approaches with an absolute increase in accuracy of up to 8% when trained on a dataset with 25% completeness (75% of training data with missing modalities). By enabling a single model to generalize across all modality configurations, our approach provides an efficient solution for real-world multi-modal medical data analysis.

Stefan Brandstätter, Maximilian Köller, Philipp Seeböck et al.

In histopathology, tissue samples are often larger than a standard microscope slide, making stitching of multiple fragments necessary to process entire structures such as tumors. Automated stitching is a prerequisite for scaling analysis, but is challenging due to possible tissue loss during preparation, inhomogeneous morphological distortion, staining inconsistencies, missing regions due to misalignment on the slide, or frayed tissue edges. This limits state-of-the-art stitching methods using boundary shape matching algorithms to reconstruct artificial whole mount slides (WMS). Here, we introduce SemanticStitcher using latent feature representations derived from a visual histopathology foundation model to identify neighboring areas in different fragments. Robust pose estimation based on a large number of semantic matching candidates derives a mosaic of multiple fragments to form the WMS. Experiments on three different histopathology datasets demonstrate that SemanticStitcher yields robust WMS mosaicing and consistently outperforms the state of the art in correct boundary matches.

Matthias Perkonigg, Nina Bastati, Ahmed Ba-Ssalamah et al.

Quantifiable image patterns associated with disease progression and treatment response are critical tools for guiding individual treatment, and for developing novel therapies. Here, we show that unsupervised machine learning can identify a pattern vocabulary of liver tissue in magnetic resonance images that quantifies treatment response in diffuse liver disease. Deep clustering networks simultaneously encode and cluster patches of medical images into a low-dimensional latent space to establish a tissue vocabulary. The resulting tissue types capture differential tissue change and its location in the liver associated with treatment response. We demonstrate the utility of the vocabulary on a randomized controlled trial cohort of non-alcoholic steatohepatitis patients. First, we use the vocabulary to compare longitudinal liver change in a placebo and a treatment cohort. Results show that the method identifies specific liver tissue change pathways associated with treatment, and enables a better separation between treatment groups than established non-imaging measures. Moreover, we show that the vocabulary can predict biopsy derived features from non-invasive imaging data. We validate the method on a separate replication cohort to demonstrate the applicability of the proposed method.

Branko Mitic, Philipp Seeböck, Jennifer Straub et al.

Fast detection of emerging diseases is important for containing their spread and treating patients effectively. Local anomalies are relevant, but often novel diseases involve familiar disease patterns in new spatial distributions. Therefore, established local anomaly detection approaches may fail to identify them as new. Here, we present a novel approach to detect the emergence of new disease phenotypes exhibiting distinct patterns of the spatial distribution of lesions. We first identify anomalies in lung CT data, and then compare their distribution in a continually acquired new patient cohorts with historic patient population observed over a long prior period. We evaluate how accumulated evidence collected in the stream of patients is able to detect the onset of an emerging disease. In a gram-matrix based representation derived from the intermediate layers of a three-dimensional convolutional neural network, newly emerging clusters indicate emerging diseases.

Matthias Perkonigg, Johannes Hofmanninger, Christian Herold et al.

Machine learning in medical imaging during clinical routine is impaired by changes in scanner protocols, hardware, or policies resulting in a heterogeneous set of acquisition settings. When training a deep learning model on an initial static training set, model performance and reliability suffer from changes of acquisition characteristics as data and targets may become inconsistent. Continual learning can help to adapt models to the changing environment by training on a continuous data stream. However, continual manual expert labelling of medical imaging requires substantial effort. Thus, ways to use labelling resources efficiently on a well chosen sub-set of new examples is necessary to render this strategy feasible. Here, we propose a method for continual active learning operating on a stream of medical images in a multi-scanner setting. The approach automatically recognizes shifts in image acquisition characteristics - new domains -, selects optimal examples for labelling and adapts training accordingly. Labelling is subject to a limited budget, resembling typical real world scenarios. To demonstrate generalizability, we evaluate the effectiveness of our method on three tasks: cardiac segmentation, lung nodule detection and brain age estimation. Results show that the proposed approach outperforms other active learning methods, while effectively counteracting catastrophic forgetting.

Athena Taymourtash, Hamza Kebiri, Sébastien Tourbier et al.

Resting-state functional Magnetic Resonance Imaging (fMRI) is a powerful imaging technique for studying functional development of the brain in utero. However, unpredictable and excessive movement of fetuses has limited clinical application since it causes substantial signal fluctuations which can systematically alter observed patterns of functional connectivity. Previous studies have focused on the accurate estimation of the motion parameters in case of large fetal head movement and used a 3D single step interpolation approach at each timepoint to recover motion-free fMRI images. This does not guarantee that the reconstructed image corresponds to the minimum error representation of fMRI time series given the acquired data. Here, we propose a novel technique based on four dimensional iterative reconstruction of the scattered slices acquired during fetal fMRI. The accuracy of the proposed method was quantitatively evaluated on a group of real clinical fMRI fetuses. The results indicate improvements of reconstruction quality compared to the conventional 3D interpolation approach.

Matthias Perkonigg, Peter Mesenbrink, Alexander Goehler et al.

In multi-center randomized clinical trials imaging data can be diverse due to acquisition technology or scanning protocols. Models predicting future outcome of patients are impaired by this data heterogeneity. Here, we propose a prediction method that can cope with a high number of different scanning sites and a low number of samples per site. We cluster sites into pseudo-domains based on visual appearance of scans, and train pseudo-domain specific models. Results show that they improve the prediction accuracy for steatosis after 48 weeks from imaging data acquired at an initial visit and 12-weeks follow-up in liver disease

Lucas Fidon, Michael Aertsen, Nada Mufti et al.

The performance of deep neural networks typically increases with the number of training images. However, not all images have the same importance towards improved performance and robustness. In fetal brain MRI, abnormalities exacerbate the variability of the developing brain anatomy compared to non-pathological cases. A small number of abnormal cases, as is typically available in clinical datasets used for training, are unlikely to fairly represent the rich variability of abnormal developing brains. This leads machine learning systems trained by maximizing the average performance to be biased toward non-pathological cases. This problem was recently referred to as hidden stratification. To be suited for clinical use, automatic segmentation methods need to reliably achieve high-quality segmentation outcomes also for pathological cases. In this paper, we show that the state-of-the-art deep learning pipeline nnU-Net has difficulties to generalize to unseen abnormal cases. To mitigate this problem, we propose to train a deep neural network to minimize a percentile of the distribution of per-volume loss over the dataset. We show that this can be achieved by using Distributionally Robust Optimization (DRO). DRO automatically reweights the training samples with lower performance, encouraging nnU-Net to perform more consistently on all cases. We validated our approach using a dataset of 368 fetal brain T2w MRIs, including 124 MRIs of open spina bifida cases and 51 MRIs of cases with other severe abnormalities of brain development.

Matthias Perkonigg, Johannes Hofmanninger, Georg Langs

Imaging in clinical routine is subject to changing scanner protocols, hardware, or policies in a typically heterogeneous set of acquisition hardware. Accuracy and reliability of deep learning models suffer from those changes as data and targets become inconsistent with their initial static training set. Continual learning can adapt to a continuous data stream of a changing imaging environment. Here, we propose a method for continual active learning on a data stream of medical images. It recognizes shifts or additions of new imaging sources - domains -, adapts training accordingly, and selects optimal examples for labelling. Model training has to cope with a limited labelling budget, resembling typical real world scenarios. We demonstrate our method on T1-weighted magnetic resonance images from three different scanners with the task of brain age estimation. Results demonstrate that the proposed method outperforms naive active learning while requiring less manual labelling.

Amirreza Mahbod, Philipp Tschandl, Georg Langs et al.

Malignant melanoma (MM) is one of the deadliest types of skin cancer. Analysing dermatoscopic images plays an important role in the early detection of MM and other pigmented skin lesions. Among different computer-based methods, deep learning-based approaches and in particular convolutional neural networks have shown excellent classification and segmentation performances for dermatoscopic skin lesion images. These models can be trained end-to-end without requiring any hand-crafted features. However, the effect of using lesion segmentation information on classification performance has remained an open question. In this study, we explicitly investigated the impact of using skin lesion segmentation masks on the performance of dermatoscopic image classification. To do this, first, we developed a baseline classifier as the reference model without using any segmentation masks. Then, we used either manually or automatically created segmentation masks in both training and test phases in different scenarios and investigated the classification performances. Evaluated on the ISIC 2017 challenge dataset which contained two binary classification tasks (i.e. MM vs. all and seborrheic keratosis (SK) vs. all) and based on the derived area under the receiver operating characteristic curve scores, we observed four main outcomes. Our results show that 1) using segmentation masks did not significantly improve the MM classification performance in any scenario, 2) in one of the scenarios (using segmentation masks for dilated cropping), SK classification performance was significantly improved, 3) removing all background information by the segmentation masks significantly degraded the overall classification performance, and 4) in case of using the appropriate scenario (using segmentation for dilated cropping), there is no significant difference of using manually or automatically created segmentation masks.

Johannes Hofmanninger, Matthias Perkonigg, James A. Brink et al.

In medical imaging, technical progress or changes in diagnostic procedures lead to a continuous change in image appearance. Scanner manufacturer, reconstruction kernel, dose, other protocol specific settings or administering of contrast agents are examples that influence image content independent of the scanned biology. Such domain and task shifts limit the applicability of machine learning algorithms in the clinical routine by rendering models obsolete over time. Here, we address the problem of data shifts in a continuous learning scenario by adapting a model to unseen variations in the source domain while counteracting catastrophic forgetting effects. Our method uses a dynamic memory to facilitate rehearsal of a diverse training data subset to mitigate forgetting. We evaluated our approach on routine clinical CT data obtained with two different scanner protocols and synthetic classification tasks. Experiments show that dynamic memory counters catastrophic forgetting in a setting with multiple data shifts without the necessity for explicit knowledge about when these shifts occur.

Johannes Hofmanninger, Sebastian Roehrich, Helmut Prosch et al.

Chest radiographs are commonly performed low-cost exams for screening and diagnosis. However, radiographs are 2D representations of 3D structures causing considerable clutter impeding visual inspection and automated image analysis. Here, we propose a Fully Convolutional Network to suppress, for a specific task, undesired visual structure from radiographs while retaining the relevant image information such as lung-parenchyma. The proposed algorithm creates reconstructed radiographs and ground-truth data from high resolution CT-scans. Results show that removing visual variation that is irrelevant for a classification task improves the performance of a classifier when only limited training data are available. This is particularly relevant because a low number of ground-truth cases is common in medical imaging.

Johannes Hofmanninger, Florian Prayer, Jeanny Pan et al.

Automated segmentation of anatomical structures is a crucial step in image analysis. For lung segmentation in computed tomography, a variety of approaches exist, involving sophisticated pipelines trained and validated on different datasets. However, the clinical applicability of these approaches across diseases remains limited. We compared four generic deep learning approaches trained on various datasets and two readily available lung segmentation algorithms. We performed evaluation on routine imaging data with more than six different disease patterns and three published data sets. Using different deep learning approaches, mean Dice similarity coefficients (DSCs) on test datasets varied not over 0.02. When trained on a diverse routine dataset (n = 36) a standard approach (U-net) yields a higher DSC (0.97 $\pm$ 0.05) compared to training on public datasets such as Lung Tissue Research Consortium (0.94 $\pm$ 0.13, p = 0.024) or Anatomy 3 (0.92 $\pm$ 0.15, p = 0.001). Trained on routine data (n = 231) covering multiple diseases, U-net compared to reference methods yields a DSC of 0.98 $\pm$ 0.03 versus 0.94 $\pm$ 0.12 (p = 0.024).

Matthias Perkonigg, Daniel Sobotka, Ahmed Ba-Ssalamah et al.

Predictive marker patterns in imaging data are a means to quantify disease and progression, but their identification is challenging, if the underlying biology is poorly understood. Here, we present a method to identify predictive texture patterns in medical images in an unsupervised way. Based on deep clustering networks, we simultaneously encode and cluster medical image patches in a low-dimensional latent space. The resulting clusters serve as features for disease staging, linking them to the underlying disease. We evaluate the method on 70 T1-weighted magnetic resonance images of patients with different stages of liver steatosis. The deep clustering approach is able to find predictive clusters with a stable ranking, differentiating between low and high steatosis with an F1-Score of 0.78.

Philipp Seeböck, José Ignacio Orlando, Thomas Schlegl et al.

Diagnosis and treatment guidance are aided by detecting relevant biomarkers in medical images. Although supervised deep learning can perform accurate segmentation of pathological areas, it is limited by requiring a-priori definitions of these regions, large-scale annotations, and a representative patient cohort in the training set. In contrast, anomaly detection is not limited to specific definitions of pathologies and allows for training on healthy samples without annotation. Anomalous regions can then serve as candidates for biomarker discovery. Knowledge about normal anatomical structure brings implicit information for detecting anomalies. We propose to take advantage of this property using bayesian deep learning, based on the assumption that epistemic uncertainties will correlate with anatomical deviations from a normal training set. A Bayesian U-Net is trained on a well-defined healthy environment using weak labels of healthy anatomy produced by existing methods. At test time, we capture epistemic uncertainty estimates of our model using Monte Carlo dropout. A novel post-processing technique is then applied to exploit these estimates and transfer their layered appearance to smooth blob-shaped segmentations of the anomalies. We experimentally validated this approach in retinal optical coherence tomography (OCT) images, using weak labels of retinal layers. Our method achieved a Dice index of 0.789 in an independent anomaly test set of age-related macular degeneration (AMD) cases. The resulting segmentations allowed very high accuracy for separating healthy and diseased cases with late wet AMD, dry geographic atrophy (GA), diabetic macular edema (DME) and retinal vein occlusion (RVO). Finally, we qualitatively observed that our approach can also detect other deviations in normal scans such as cut edge artifacts.

Philipp Seeböck, David Romo-Bucheli, Sebastian Waldstein et al.

Optical coherence tomography (OCT) has become the most important imaging modality in ophthalmology. A substantial amount of research has recently been devoted to the development of machine learning (ML) models for the identification and quantification of pathological features in OCT images. Among the several sources of variability the ML models have to deal with, a major factor is the acquisition device, which can limit the ML model's generalizability. In this paper, we propose to reduce the image variability across different OCT devices (Spectralis and Cirrus) by using CycleGAN, an unsupervised unpaired image transformation algorithm. The usefulness of this approach is evaluated in the setting of retinal fluid segmentation, namely intraretinal cystoid fluid (IRC) and subretinal fluid (SRF). First, we train a segmentation model on images acquired with a source OCT device. Then we evaluate the model on (1) source, (2) target and (3) transformed versions of the target OCT images. The presented transformation strategy shows an F1 score of 0.4 (0.51) for IRC (SRF) segmentations. Compared with traditional transformation approaches, this means an F1 score gain of 0.2 (0.12).

Philipp Seeböck, Sebastian M. Waldstein, Sophie Klimscha et al.

The identification and quantification of markers in medical images is critical for diagnosis, prognosis, and disease management. Supervised machine learning enables the detection and exploitation of findings that are known a priori after annotation of training examples by experts. However, supervision does not scale well, due to the amount of necessary training examples, and the limitation of the marker vocabulary to known entities. In this proof-of-concept study, we propose unsupervised identification of anomalies as candidates for markers in retinal Optical Coherence Tomography (OCT) imaging data without a constraint to a priori definitions. We identify and categorize marker candidates occurring frequently in the data, and demonstrate that these markers show predictive value in the task of detecting disease. A careful qualitative analysis of the identified data driven markers reveals how their quantifiable occurrence aligns with our current understanding of disease course, in early- and late age-related macular degeneration (AMD) patients. A multi-scale deep denoising autoencoder is trained on healthy images, and a one-class support vector machine identifies anomalies in new data. Clustering in the anomalies identifies stable categories. Using these markers to classify healthy-, early AMD- and late AMD cases yields an accuracy of 81.40%. In a second binary classification experiment on a publicly available data set (healthy vs. intermediate AMD) the model achieves an area under the ROC curve of 0.944.

Christian Wachinger, Matthew Toews, Georg Langs et al.

We introduce an approach for image segmentation based on sparse correspondences between keypoints in testing and training images. Keypoints represent automatically identified distinctive image locations, where each keypoint correspondence suggests a transformation between images. We use these correspondences to transfer label maps of entire organs from the training images to the test image. The keypoint transfer algorithm includes three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ segmentations. We report segmentation results for abdominal organs in whole-body CT and MRI, as well as in contrast-enhanced CT and MRI. Our method offers a speed-up of about three orders of magnitude in comparison to common multi-atlas segmentation, while achieving an accuracy that compares favorably. Moreover, keypoint transfer does not require the registration to an atlas or a training phase. Finally, the method allows for the segmentation of scans with highly variable field-of-view.

Thomas Schlegl, Hrvoje Bogunovic, Sophie Klimscha et al.

The automatic detection of disease related entities in retinal imaging data is relevant for disease- and treatment monitoring. It enables the quantitative assessment of large amounts of data and the corresponding study of disease characteristics. The presence of hyperreflective foci (HRF) is related to disease progression in various retinal diseases. Manual identification of HRF in spectral-domain optical coherence tomography (SD-OCT) scans is error-prone and tedious. We present a fully automated machine learning approach for segmenting HRF in SD-OCT scans. Evaluation on annotated OCT images of the retina demonstrates that a residual U-Net allows to segment HRF with high accuracy. As our dataset comprised data from different retinal diseases including age-related macular degeneration, diabetic macular edema and retinal vein occlusion, the algorithm can safely be applied in all of them though different pathophysiological origins are known.

Thomas Schlegl, Philipp Seeböck, Sebastian M. Waldstein et al.

Obtaining models that capture imaging markers relevant for disease progression and treatment monitoring is challenging. Models are typically based on large amounts of data with annotated examples of known markers aiming at automating detection. High annotation effort and the limitation to a vocabulary of known markers limit the power of such approaches. Here, we perform unsupervised learning to identify anomalies in imaging data as candidates for markers. We propose AnoGAN, a deep convolutional generative adversarial network to learn a manifold of normal anatomical variability, accompanying a novel anomaly scoring scheme based on the mapping from image space to a latent space. Applied to new data, the model labels anomalies, and scores image patches indicating their fit into the learned distribution. Results on optical coherence tomography images of the retina demonstrate that the approach correctly identifies anomalous images, such as images containing retinal fluid or hyperreflective foci.

Leila Wehbe, Anwar Nunez-Elizalde, Marcel van Gerven et al.

This workshop explores the interface between cognitive neuroscience and recent advances in AI fields that aim to reproduce human performance such as natural language processing and computer vision, and specifically deep learning approaches to such problems. When studying the cognitive capabilities of the brain, scientists follow a system identification approach in which they present different stimuli to the subjects and try to model the response that different brain areas have of that stimulus. The goal is to understand the brain by trying to find the function that expresses the activity of brain areas in terms of different properties of the stimulus. Experimental stimuli are becoming increasingly complex with more and more people being interested in studying real life phenomena such as the perception of natural images or natural sentences. There is therefore a need for a rich and adequate vector representation of the properties of the stimulus, that we can obtain using advances in machine learning. In parallel, new ML approaches, many of which in deep learning, are inspired to a certain extent by human behavior or biological principles. Neural networks for example were originally inspired by biological neurons. More recently, processes such as attention are being used which have are inspired by human behavior. However, the large bulk of these methods are independent of findings about brain function, and it is unclear whether it is at all beneficial for machine learning to try to emulate brain function in order to achieve the same tasks that the brain achieves.

Philipp Seeböck, Sebastian Waldstein, Sophie Klimscha et al.

The identification and quantification of markers in medical images is critical for diagnosis, prognosis and management of patients in clinical practice. Supervised- or weakly supervised training enables the detection of findings that are known a priori. It does not scale well, and a priori definition limits the vocabulary of markers to known entities reducing the accuracy of diagnosis and prognosis. Here, we propose the identification of anomalies in large-scale medical imaging data using healthy examples as a reference. We detect and categorize candidates for anomaly findings untypical for the observed data. A deep convolutional autoencoder is trained on healthy retinal images. The learned model generates a new feature representation, and the distribution of healthy retinal patches is estimated by a one-class support vector machine. Results demonstrate that we can identify pathologic regions in images without using expert annotations. A subsequent clustering categorizes findings into clinically meaningful classes. In addition the learned features outperform standard embedding approaches in a classification task.