Sophie Starck

Özgün Turgut, Philip Müller, Paul Hager et al.

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. Our entire pipeline is publicly available at https://github.com/oetu/MMCL-ECG-CMR.

Sophie Starck, Yadunandan Vivekanand Kini, Jessica Johanna Maria Ritter et al.

Age prediction is an important part of medical assessments and research. It can aid in detecting diseases as well as abnormal ageing by highlighting potential discrepancies between chronological and biological age. To improve understanding of age-related changes in various body parts, we investigate the ageing of the human body on a large scale by using whole-body 3D images. We utilise the Grad-CAM method to determine the body areas most predictive of a person's age. In order to expand our analysis beyond individual subjects, we employ registration techniques to generate population-wide importance maps that show the most predictive areas in the body for a whole cohort of subjects. We show that the investigation of the full 3D volume of the whole body and the population-wide analysis can give important insights into which body parts play the most important roles in predicting a person's age. Our findings reveal three primary areas of interest: the spine, the autochthonous back muscles, and the cardiac region, which exhibits the highest importance. Finally, we investigate differences between subjects that show accelerated and decelerated ageing.

Kyriaki-Margarita Bintsi, Tamara T. Mueller, Sophie Starck et al.

The difference between the chronological and biological brain age of a subject can be an important biomarker for neurodegenerative diseases, thus brain age estimation can be crucial in clinical settings. One way to incorporate multimodal information into this estimation is through population graphs, which combine various types of imaging data and capture the associations among individuals within a population. In medical imaging, population graphs have demonstrated promising results, mostly for classification tasks. In most cases, the graph structure is pre-defined and remains static during training. However, extracting population graphs is a non-trivial task and can significantly impact the performance of Graph Neural Networks (GNNs), which are sensitive to the graph structure. In this work, we highlight the importance of a meaningful graph construction and experiment with different population-graph construction methods and their effect on GNN performance on brain age estimation. We use the homophily metric and graph visualizations to gain valuable quantitative and qualitative insights on the extracted graph structures. For the experimental evaluation, we leverage the UK Biobank dataset, which offers many imaging and non-imaging phenotypes. Our results indicate that architectures highly sensitive to the graph structure, such as Graph Convolutional Network (GCN) and Graph Attention Network (GAT), struggle with low homophily graphs, while other architectures, such as GraphSage and Chebyshev, are more robust across different homophily ratios. We conclude that static graph construction approaches are potentially insufficient for the task of brain age estimation and make recommendations for alternative research directions.

Tamara T. Mueller, Siyu Zhou, Sophie Starck et al.

Body fat volume and distribution can be a strong indication for a person's overall health and the risk for developing diseases like type 2 diabetes and cardiovascular diseases. Frequently used measures for fat estimation are the body mass index (BMI), waist circumference, or the waist-hip-ratio. However, those are rather imprecise measures that do not allow for a discrimination between different types of fat or between fat and muscle tissue. The estimation of visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissue volume has shown to be a more accurate measure for named risk factors. In this work, we show that triangulated body surface meshes can be used to accurately predict VAT and ASAT volumes using graph neural networks. Our methods achieve high performance while reducing training time and required resources compared to state-of-the-art convolutional neural networks in this area. We furthermore envision this method to be applicable to cheaper and easily accessible medical surface scans instead of expensive medical images.

Tamara T. Mueller, Sophie Starck, Leonhard F. Feiner et al.

When re-structuring patient cohorts into so-called population graphs, initially independent data points can be incorporated into one interconnected graph structure. This population graph can then be used for medical downstream tasks using graph neural networks (GNNs). The construction of a suitable graph structure is a challenging step in the learning pipeline that can have severe impact on model performance. To this end, different graph assessment metrics have been introduced to evaluate graph structures. However, these metrics are limited to classification tasks and discrete adjacency matrices, only covering a small subset of real-world applications. In this work, we introduce extended graph assessment metrics (GAMs) for regression tasks and continuous adjacency matrices. We focus on two GAMs in specific: \textit{homophily} and \textit{cross-class neighbourhood similarity} (CCNS). We extend the notion of GAMs to more than one hop, define homophily for regression tasks, as well as continuous adjacency matrices, and propose a light-weight CCNS distance for discrete and continuous adjacency matrices. We show the correlation of these metrics with model performance on different medical population graphs and under different learning settings.

Busra Nur Zeybek, Özgün Turgut, Yundi Zhang et al.

Cardiovascular diseases are the leading cause of death. Cardiac phenotypes (CPs), e.g., ejection fraction, are the gold standard for assessing cardiac health, but they are derived from cine cardiac magnetic resonance imaging (CMR), which is costly and requires high spatio-temporal resolution. Every magnetic resonance (MR) examination begins with rapid and coarse localizers for scan planning, which are discarded thereafter. Despite non-diagnostic image quality and lack of temporal information, localizers can provide valuable structural information rapidly. In addition to imaging, patient-level information, including demographics and lifestyle, influence the cardiac health assessment. Electrocardiograms (ECGs) are inexpensive, routinely ordered in clinical practice, and capture the temporal activity of the heart. Here, we introduce C-TRIP (Cardiac Tri-modal Representations for Imaging Phenotypes), a multi-modal framework that aligns localizer MRI, ECG signals, and tabular metadata to learn a robust latent space and predict CPs using localizer images as an opportunistic alternative to CMR. By combining these three modalities, we leverage cheap spatial and temporal information from localizers, and ECG, respectively while benefiting from patient-specific context provided by tabular data. Our pipeline consists of three stages. First, encoders are trained independently to learn uni-modal representations. The second stage fuses the pre-trained encoders to unify the latent space. The final stage uses the enriched representation space for CP prediction, with inference performed exclusively on localizer MRI. Proposed C-TRIP yields accurate functional CPs, and high correlations for structural CPs. Since localizers are inherently rapid and low-cost, our C-TRIP framework could enable better accessibility for CP estimation.

Dmitrii Seletkov, Sophie Starck, Ayhan Can Erdur et al.

Reliable preclinical disease risk assessment is essential to move public healthcare from reactive treatment to proactive identification and prevention. However, image-based risk prediction algorithms often consider one condition at a time and depend on hand-crafted features obtained through segmentation tools. We propose a whole-body self-supervised representation learning method for the preclinical disease risk assessment under a competing risk modeling. This approach outperforms whole-body radiomics in multiple diseases, including cardiovascular disease (CVD), type 2 diabetes (T2D), chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD). Simulating a preclinical screening scenario and subsequently combining with cardiac MRI, it sharpens further the prediction for CVD subgroups: ischemic heart disease (IHD), hypertensive diseases (HD), and stroke. The results indicate the translational potential of whole-body representations as a standalone screening modality and as part of a multi-modal framework within clinical workflows for early personalized risk stratification. The code is available at https://github.com/yayapa/WBRLforCR/

Maik Dannecker, Vasiliki Sideri-Lampretsa, Sophie Starck et al.

Magnetic resonance imaging of fetal and neonatal brains reveals rapid neurodevelopment marked by substantial anatomical changes unfolding within days. Studying this critical stage of the developing human brain, therefore, requires accurate brain models-referred to as atlases-of high spatial and temporal resolution. To meet these demands, established traditional atlases and recently proposed deep learning-based methods rely on large and comprehensive datasets. This poses a major challenge for studying brains in the presence of pathologies for which data remains scarce. We address this limitation with CINeMA (Conditional Implicit Neural Multi-Modal Atlas), a novel framework for creating high-resolution, spatio-temporal, multimodal brain atlases, suitable for low-data settings. Unlike established methods, CINeMA operates in latent space, avoiding compute-intensive image registration and reducing atlas construction times from days to minutes. Furthermore, it enables flexible conditioning on anatomical features including GA, birth age, and pathologies like ventriculomegaly (VM) and agenesis of the corpus callosum (ACC). CINeMA supports downstream tasks such as tissue segmentation and age prediction whereas its generative properties enable synthetic data creation and anatomically informed data augmentation. Surpassing state-of-the-art methods in accuracy, efficiency, and versatility, CINeMA represents a powerful tool for advancing brain research. We release the code and atlases at https://github.com/m-dannecker/CINeMA.

Vasiliki Sideri-Lampretsa, Sophie Starck, Robbie Holland et al.

Reusing the early layers of cohort-trained INRs as initialization for new signals has been shown to accelerate and improve signal fitting, yet it remains unclear which layers of the shared encoder learn transferable representations and what those representations encode. We address both questions for two standard backbones, SIREN and Fourier-feature MLPs (FFMLP). First, sweeping the freeze depth across the shared encoder at test time, we find that the optimum coincides with the layer of highest weight stable rank. Moreover, freezing at this depth matches or improves on the standard fine-tuning recipe across all our experiments. Second, identifying which layer transfers does not characterize what that layer encodes. To address this we adopt sparse autoencoders (SAEs), the dominant tool in mechanistic interpretability, and present the first SAE decomposition of INR activations into sparse dictionary atoms. Interestingly, SIREN and FFMLP achieve comparable cohort-fitting quality, but learn qualitatively different dictionaries. Cohort SIREN's atoms are localized, tiling the coordinate plane such that each atom fires in a confined region independent of cohort content. Cohort FFMLP's atoms are image-spanning, tracing the contours of memorized cohort signals. Single-atom ablations confirm causal use of these dictionaries: a single FFMLP atom out of 4096 can drop PSNR by up to 10.6 dB across the image, while SIREN ablations remain confined to where the atom fires. Together, these results give the first mechanistic account of what transfers in cohort-trained INRs and turn their activations into inspectable dictionary atoms. These tools open a path towards characterizing what INRs encode and towards architectures designed for generalization rather than memorization.

Sophie Starck, Vasiliki Sideri-Lampretsa, Bernhard Kainz et al.

Anatomical atlases are widely used for population studies and analysis. Conditional atlases target a specific sub-population defined via certain conditions, such as demographics or pathologies, and allow for the investigation of fine-grained anatomical differences like morphological changes associated with ageing or disease. Existing approaches use either registration-based methods that are often unable to handle large anatomical variations or generative adversarial models, which are challenging to train since they can suffer from training instabilities. Instead of generating atlases directly in as intensities, we propose using latent diffusion models to generate deformation fields, which transform a general population atlas into one representing a specific sub-population. Our approach ensures structural integrity, enhances interpretability and avoids hallucinations that may arise during direct image synthesis by generating this deformation field and regularising it using a neighbourhood of images. We compare our method to several state-of-the-art atlas generation methods using brain MR images from the UK Biobank. Our method generates highly realistic atlases with smooth transformations and high anatomical fidelity, outperforming existing baselines. We demonstrate the quality of these atlases through comprehensive evaluations, including quantitative metrics for anatomical accuracy, perceptual similarity, and qualitative analyses displaying the consistency and realism of the generated atlases.

Robert Graf, Hendrik Möller, Sophie Starck et al.

Volume Interpolated Breath-Hold Examination (VIBE) MRI generates images suitable for water and fat signal composition estimation. While the two-point VIBE provides water-fat-separated images, the six-point VIBE allows estimation of the effective transversal relaxation rate R2* and the proton density fat fraction (PDFF), which are imaging markers for health and disease. Ambiguity during signal reconstruction can lead to water-fat swaps. This shortcoming challenges the application of VIBE-MRI for automated PDFF analyses of large-scale clinical data and of population studies. This study develops an automated pipeline to detect and correct water-fat swaps in non-contrast-enhanced VIBE images. Our three-step pipeline begins with training a segmentation network to classify volumes as "fat-like" or "water-like," using synthetic water-fat swaps generated by merging fat and water volumes with Perlin noise. Next, a denoising diffusion image-to-image network predicts water volumes as signal priors for correction. Finally, we integrate this prior into a physics-constrained model to recover accurate water and fat signals. Our approach achieves a < 1% error rate in water-fat swap detection for a 6-point VIBE. Notably, swaps disproportionately affect individuals in the Underweight and Class 3 Obesity BMI categories. Our correction algorithm ensures accurate solution selection in chemical phase MRIs, enabling reliable PDFF estimation. This forms a solid technical foundation for automated large-scale population imaging analysis.

Robert Graf, Florian Hunecke, Soeren Pohl et al.

Deep learning has made significant strides in medical imaging, leveraging the use of large datasets to improve diagnostics and prognostics. However, large datasets often come with inherent errors through subject selection and acquisition. In this paper, we investigate the use of Diffusion Autoencoder (DAE) embeddings for uncovering and understanding data characteristics and biases, including biases for protected variables like sex and data abnormalities indicative of unwanted protocol variations. We use sagittal T2-weighted magnetic resonance (MR) images of the neck, chest, and lumbar region from 11186 German National Cohort (NAKO) participants. We compare DAE embeddings with existing generative models like StyleGAN and Variational Autoencoder. Evaluations on a large-scale dataset consisting of sagittal T2-weighted MR images of three spine regions show that DAE embeddings effectively separate protected variables such as sex and age. Furthermore, we used t-SNE visualization to identify unwanted variations in imaging protocols, revealing differences in head positioning. Our embedding can identify samples where a sex predictor will have issues learning the correct sex. Our findings highlight the potential of using advanced embedding techniques like DAEs to detect data quality issues and biases in medical imaging datasets. Identifying such hidden relations can enhance the reliability and fairness of deep learning models in healthcare applications, ultimately improving patient care and outcomes.

Yundi Zhang, Chen Chen, Suprosanna Shit et al.

Cardiac Magnetic Resonance (CMR) imaging serves as the gold-standard for evaluating cardiac morphology and function. Typically, a multi-view CMR stack, covering short-axis (SA) and 2/3/4-chamber long-axis (LA) views, is acquired for a thorough cardiac assessment. However, efficiently streamlining the complex, high-dimensional 3D+T CMR data and distilling compact, coherent representation remains a challenge. In this work, we introduce a whole-heart self-supervised learning framework that utilizes masked imaging modeling to automatically uncover the correlations between spatial and temporal patches throughout the cardiac stacks. This process facilitates the generation of meaningful and well-clustered heart representations without relying on the traditionally required, and often costly, labeled data. The learned heart representation can be directly used for various downstream tasks. Furthermore, our method demonstrates remarkable robustness, ensuring consistent representations even when certain CMR planes are missing/flawed. We train our model on 14,000 unlabeled CMR data from UK BioBank and evaluate it on 1,000 annotated data. The proposed method demonstrates superior performance to baselines in tasks that demand comprehensive 3D+T cardiac information, e.g. cardiac phenotype (ejection fraction and ventricle volume) prediction and multi-plane/multi-frame CMR segmentation, highlighting its effectiveness in extracting comprehensive cardiac features that are both anatomically and pathologically relevant.