Fabian Bongratz

Fabian Bongratz, Anne-Marie Rickmann, Sebastian Pölsterl et al.

The reconstruction of cortical surfaces from brain magnetic resonance imaging (MRI) scans is essential for quantitative analyses of cortical thickness and sulcal morphology. Although traditional and deep learning-based algorithmic pipelines exist for this purpose, they have two major drawbacks: lengthy runtimes of multiple hours (traditional) or intricate post-processing, such as mesh extraction and topology correction (deep learning-based). In this work, we address both of these issues and propose Vox2Cortex, a deep learning-based algorithm that directly yields topologically correct, three-dimensional meshes of the boundaries of the cortex. Vox2Cortex leverages convolutional and graph convolutional neural networks to deform an initial template to the densely folded geometry of the cortex represented by an input MRI scan. We show in extensive experiments on three brain MRI datasets that our meshes are as accurate as the ones reconstructed by state-of-the-art methods in the field, without the need for time- and resource-intensive post-processing. To accurately reconstruct the tightly folded cortex, we work with meshes containing about 168,000 vertices at test time, scaling deep explicit reconstruction methods to a new level.

Anne-Marie Rickmann, Fabian Bongratz, Sebastian Pölsterl et al.

The reconstruction of cerebral cortex surfaces from brain MRI scans is instrumental for the analysis of brain morphology and the detection of cortical thinning in neurodegenerative diseases like Alzheimer's disease (AD). Moreover, for a fine-grained analysis of atrophy patterns, the parcellation of the cortical surfaces into individual brain regions is required. For the former task, powerful deep learning approaches, which provide highly accurate brain surfaces of tissue boundaries from input MRI scans in seconds, have recently been proposed. However, these methods do not come with the ability to provide a parcellation of the reconstructed surfaces. Instead, separate brain-parcellation methods have been developed, which typically consider the cortical surfaces as given, often computed beforehand with FreeSurfer. In this work, we propose two options, one based on a graph classification branch and another based on a novel generic 3D reconstruction loss, to augment template-deformation algorithms such that the surface meshes directly come with an atlas-based brain parcellation. By combining both options with two of the latest cortical surface reconstruction algorithms, we attain highly accurate parcellations with a Dice score of 90.2 (graph classification branch) and 90.4 (novel reconstruction loss) together with state-of-the-art surfaces.

Fabian Bongratz, Anne-Marie Rickmann, Christian Wachinger

Abdominal organ segmentation from CT and MRI is an essential prerequisite for surgical planning and computer-aided navigation systems. It is challenging due to the high variability in the shape, size, and position of abdominal organs. Three-dimensional numeric representations of abdominal shapes with point-wise correspondence to a template are further important for quantitative and statistical analyses thereof. Recently, template-based surface extraction methods have shown promising advances for direct mesh reconstruction from volumetric scans. However, the generalization of these deep learning-based approaches to different organs and datasets, a crucial property for deployment in clinical environments, has not yet been assessed. We close this gap and employ template-based mesh reconstruction methods for joint liver, kidney, pancreas, and spleen segmentation. Our experiments on manually annotated CT and MRI data reveal limited generalization capabilities of previous methods to organs of different geometry and weak performance on small datasets. We alleviate these issues with a novel deep diffeomorphic mesh-deformation architecture and an improved training scheme. The resulting method, UNetFlow, generalizes well to all four organs and can be easily fine-tuned on new data. Moreover, we propose a simple registration-based post-processing that aligns voxel and mesh outputs to boost segmentation accuracy.

Fabian Bongratz, Vladimir Golkov, Lukas Mautner et al.

The field of reinforcement learning offers a large variety of concepts and methods to tackle sequential decision-making problems. This variety has become so large that choosing an algorithm for a task at hand can be challenging. In this work, we streamline the process of choosing reinforcement-learning algorithms and action-distribution families. We provide a structured overview of existing methods and their properties, as well as guidelines for when to choose which methods. An interactive version of these guidelines is available online at https://rl-picker.github.io/.

Fabian Bongratz, Yitong Li, Sama Elbaroudy et al.

Synthetic neuroimaging data can mitigate critical limitations of real-world datasets, including the scarcity of rare phenotypes, domain shifts across scanners, and insufficient longitudinal coverage. However, existing generative models largely rely on weak conditioning signals, such as labels or text, which lack anatomical grounding and often produce biologically implausible outputs. To this end, we introduce Cor2Vox, a cortex-grounded generative framework for brain magnetic resonance image (MRI) synthesis that ties image generation to continuous structural priors of the cerebral cortex. It leverages high-resolution cortical surfaces to guide a 3D shape-to-image Brownian bridge diffusion process, enabling topologically faithful synthesis and precise control over underlying anatomies. To support the generation of new, realistic brain shapes, we developed a large-scale statistical shape model of cortical morphology derived from over 33,000 UK Biobank scans. We validated the fidelity of Cor2Vox based on traditional image quality metrics, advanced cortical surface reconstruction, and whole-brain segmentation quality, outperforming many baseline methods. Across three applications, namely (i) anatomically consistent synthesis, (ii) simulation of progressive gray matter atrophy, and (iii) harmonization of in-house frontotemporal dementia scans with public datasets, Cor2Vox preserved fine-grained cortical morphology at the sub-voxel level, exhibiting remarkable robustness to variations in cortical geometry and disease phenotype without retraining.

Fabian Bongratz, Yitong Li, Sama Elbaroudy et al.

Despite recent advances in medical image generation, existing methods struggle to produce anatomically plausible 3D structures. In synthetic brain magnetic resonance images (MRIs), characteristic fissures are often missing, and reconstructed cortical surfaces appear scattered rather than densely convoluted. To address this issue, we introduce Cor2Vox, the first diffusion model-based method that translates continuous cortical shape priors to synthetic brain MRIs. To achieve this, we leverage a Brownian bridge process which allows for direct structured mapping between shape contours and medical images. Specifically, we adapt the concept of the Brownian bridge diffusion model to 3D and extend it to embrace various complementary shape representations. Our experiments demonstrate significant improvements in the geometric accuracy of reconstructed structures compared to previous voxel-based approaches. Moreover, Cor2Vox excels in image quality and diversity, yielding high variation in non-target structures like the skull. Finally, we highlight the capability of our approach to simulate cortical atrophy at the sub-voxel level. Our code is available at https://github.com/ai-med/Cor2Vox.

Fabian Bongratz, Anne-Marie Rickmann, Christian Wachinger

The reconstruction of cortical surfaces is a prerequisite for quantitative analyses of the cerebral cortex in magnetic resonance imaging (MRI). Existing segmentation-based methods separate the surface registration from the surface extraction, which is computationally inefficient and prone to distortions. We introduce Vox2Cortex-Flow (V2C-Flow), a deep mesh-deformation technique that learns a deformation field from a brain template to the cortical surfaces of an MRI scan. To this end, we present a geometric neural network that models the deformation-describing ordinary differential equation in a continuous manner. The network architecture comprises convolutional and graph-convolutional layers, which allows it to work with images and meshes at the same time. V2C-Flow is not only very fast, requiring less than two seconds to infer all four cortical surfaces, but also establishes vertex-wise correspondences to the template during reconstruction. In addition, V2C-Flow is the first approach for cortex reconstruction that models white matter and pial surfaces jointly, therefore avoiding intersections between them. Our comprehensive experiments on internal and external test data demonstrate that V2C-Flow results in cortical surfaces that are state-of-the-art in terms of accuracy. Moreover, we show that the established correspondences are more consistent than in FreeSurfer and that they can directly be utilized for cortex parcellation and group analyses of cortical thickness.

Tom Nuno Wolf, Fabian Bongratz, Anne-Marie Rickmann et al.

Explaining predictions of black-box neural networks is crucial when applied to decision-critical tasks. Thus, attribution maps are commonly used to identify important image regions, despite prior work showing that humans prefer explanations based on similar examples. To this end, ProtoPNet learns a set of class-representative feature vectors (prototypes) for case-based reasoning. During inference, similarities of latent features to prototypes are linearly classified to form predictions and attribution maps are provided to explain the similarity. In this work, we evaluate whether architectures for case-based reasoning fulfill established axioms required for faithful explanations using the example of ProtoPNet. We show that such architectures allow the extraction of faithful explanations. However, we prove that the attribution maps used to explain the similarities violate the axioms. We propose a new procedure to extract explanations for trained ProtoPNets, named ProtoPFaith. Conceptually, these explanations are Shapley values, calculated on the similarity scores of each prototype. They allow to faithfully answer which prototypes are present in an unseen image and quantify each pixel's contribution to that presence, thereby complying with all axioms. The theoretical violations of ProtoPNet manifest in our experiments on three datasets (CUB-200-2011, Stanford Dogs, RSNA) and five architectures (ConvNet, ResNet, ResNet50, WideResNet50, ResNeXt50). Our experiments show a qualitative difference between the explanations given by ProtoPNet and ProtoPFaith. Additionally, we quantify the explanations with the Area Over the Perturbation Curve, on which ProtoPFaith outperforms ProtoPNet on all experiments by a factor $>10^3$.

Bailiang Jian, Jiazhen Pan, Yitong Li et al.

Longitudinal brain analysis is essential for understanding healthy aging and identifying pathological deviations. Longitudinal registration of sequential brain MRI underpins such analyses. However, existing methods are limited by reliance on densely sampled time series, a trade-off between accuracy and temporal smoothness, and an inability to prospectively forecast future brain states. To overcome these challenges, we introduce \emph{TimeFlow}, a learning-based framework for longitudinal brain MRI registration. TimeFlow uses a U-Net backbone with temporal conditioning to model neuroanatomy as a continuous function of age. Given only two scans from an individual, TimeFlow estimates accurate and temporally coherent deformation fields, enabling non-linear extrapolation to predict future brain states. This is achieved by our proposed inter-/extra-polation consistency constraints applied to both the deformation fields and deformed images. Remarkably, these constraints preserve temporal consistency and continuity without requiring explicit smoothness regularizers or densely sampled sequential data. Extensive experiments demonstrate that TimeFlow outperforms state-of-the-art methods in terms of both future timepoint forecasting and registration accuracy. Moreover, TimeFlow supports novel biological brain aging analyses by differentiating neurodegenerative trajectories from normal aging without requiring segmentation, thereby eliminating the need for labor-intensive annotations and mitigating segmentation inconsistency. TimeFlow offers an accurate, data-efficient, and annotation-free framework for longitudinal analysis of brain aging and chronic diseases, capable of forecasting brain changes beyond the observed study period.

Fabian Bongratz, Jan Fecht, Anne-Marie Rickmann et al.

Reconstructing the cortex from longitudinal magnetic resonance imaging (MRI) is indispensable for analyzing morphological alterations in the human brain. Despite the recent advancement of cortical surface reconstruction with deep learning, challenges arising from longitudinal data are still persistent. Especially the lack of strong spatiotemporal point correspondence between highly convoluted brain surfaces hinders downstream analyses, as local morphology is not directly comparable if the anatomical location is not matched precisely. To address this issue, we present V2C-Long, the first dedicated deep learning-based cortex reconstruction method for longitudinal MRI. V2C-Long exhibits strong inherent spatiotemporal correspondence across subjects and visits, thereby reducing the need for surface-based post-processing. We establish this correspondence directly during the reconstruction via the composition of two deep template-deformation networks and innovative aggregation of within-subject templates in mesh space. We validate V2C-Long on two large neuroimaging studies, focusing on surface accuracy, consistency, generalization, test-retest reliability, and sensitivity. The results reveal a substantial improvement in longitudinal consistency and accuracy compared to existing methods. In addition, we demonstrate stronger evidence for longitudinal cortical atrophy in Alzheimer's disease than longitudinal FreeSurfer.

Patrick Madlindl, Fabian Bongratz, Christian Wachinger

Cortical surface reconstruction (CSR) from magnetic resonance imaging (MRI) is fundamental to neuroimage analysis, enabling morphological studies of the cerebral cortex and functional brain mapping. Recent advances in learning-based CSR have dramatically accelerated processing, allowing for reconstructions through the deformation of anatomical templates within seconds. However, ensuring the learned deformations are optimal in terms of deformation energy and consistent across training runs remains a particular challenge. In this work, we design a Minimal Energy Deformation (MED) loss, acting as a regularizer on the deformation trajectories and complementing the widely used Chamfer distance in CSR. We incorporate it into the recent V2C-Flow model and demonstrate considerable improvements in previously neglected training consistency and reproducibility without harming reconstruction accuracy and topological correctness.

Ivan Stoyanov, Fabian Bongratz, Christian Wachinger

Accurate forecasting of individualized, high-resolution cortical thickness (CTh) trajectories is essential for detecting subtle cortical changes, providing invaluable insights into neurodegenerative processes and facilitating earlier and more precise intervention strategies. However, CTh forecasting is a challenging task due to the intricate non-Euclidean geometry of the cerebral cortex and the need to integrate multi-modal data for subject-specific predictions. To address these challenges, we introduce the Spherical Brownian Bridge Diffusion Model (SBDM). Specifically, we propose a bidirectional conditional Brownian bridge diffusion process to forecast CTh trajectories at the vertex level of registered cortical surfaces. Our technical contribution includes a new denoising model, the conditional spherical U-Net (CoS-UNet), which combines spherical convolutions and dense cross-attention to integrate cortical surfaces and tabular conditions seamlessly. Compared to previous approaches, SBDM achieves significantly reduced prediction errors, as demonstrated by our experiments based on longitudinal datasets from the ADNI and OASIS. Additionally, we demonstrate SBDM's ability to generate individual factual and counterfactual CTh trajectories, offering a novel framework for exploring hypothetical scenarios of cortical development.

Fabian Bongratz, Tom Nuno Wolf, Jaume Gual Ramon et al.

Interpretable models are crucial for supporting clinical decision-making, driving advances in their development and application for medical images. However, the nature of 3D volumetric data makes it inherently challenging to visualize and interpret intricate and complex structures like the cerebral cortex. Cortical surface renderings, on the other hand, provide a more accessible and understandable 3D representation of brain anatomy, facilitating visualization and interactive exploration. Motivated by this advantage and the widespread use of surface data for studying neurological disorders, we present the eXplainable Surface Vision Transformer (X-SiT). This is the first inherently interpretable neural network that offers human-understandable predictions based on interpretable cortical features. As part of X-SiT, we introduce a prototypical surface patch decoder for classifying surface patch embeddings, incorporating case-based reasoning with spatially corresponding cortical prototypes. The results demonstrate state-of-the-art performance in detecting Alzheimer's disease and frontotemporal dementia while additionally providing informative prototypes that align with known disease patterns and reveal classification errors.

Tom Nuno Wolf, Emre Kavak, Fabian Bongratz et al.

The deployment of deep learning models in critical domains necessitates a balance between high accuracy and interpretability. We introduce SIC, an inherently interpretable neural network that provides local and global explanations of its decision-making process. Leveraging the concept of case-based reasoning, SIC extracts class-representative support vectors from training images, ensuring they capture relevant features while suppressing irrelevant ones. Classification decisions are made by calculating and aggregating similarity scores between these support vectors and the input's latent feature vector. We employ B-Cos transformations, which align model weights with inputs, to yield coherent pixel-level explanations in addition to global explanations of case-based reasoning. We evaluate SIC on three tasks: fine-grained classification on Stanford Dogs and FunnyBirds, multi-label classification on Pascal VOC, and pathology detection on the RSNA dataset. Results indicate that SIC not only achieves competitive accuracy compared to state-of-the-art black-box and inherently interpretable models but also offers insightful explanations verified through practical evaluation on the FunnyBirds benchmark. Our theoretical analysis proves that these explanations fulfill established axioms for explanations. Our findings underscore SIC's potential for applications where understanding model decisions is as critical as the decisions themselves.

Fabian Bongratz, Markus Karmann, Adrian Holz et al.

Meningeal lymphatic vessels (MLVs) are responsible for the drainage of waste products from the human brain. An impairment in their functionality has been associated with aging as well as brain disorders like multiple sclerosis and Alzheimer's disease. However, MLVs have only recently been described for the first time in magnetic resonance imaging (MRI), and their ramified structure renders manual segmentation particularly difficult. Further, as there is no consistent notion of their appearance, human-annotated MLV structures contain a high inter-rater variability that most automatic segmentation methods cannot take into account. In this work, we propose a new rater-aware training scheme for the popular nnU-Net model, and we explore rater-based ensembling strategies for accurate and consistent segmentation of MLVs. This enables us to boost nnU-Net's performance while obtaining explicit predictions in different annotation styles and a rater-based uncertainty estimation. Our final model, MLV$^2$-Net, achieves a Dice similarity coefficient of 0.806 with respect to the human reference standard. The model further matches the human inter-rater reliability and replicates age-related associations with MLV volume.

Christian Wachinger, Dennis Hedderich, Melissa Thalhammer et al.

Understanding individual differences in cortical structure is key to advancing diagnostics in neurology and psychiatry. Reference models aid in detecting aberrant cortical thickness, yet site-specific biases limit their direct application to unseen data, and region-wise averages prevent the detection of localized cortical changes. To address these limitations, we developed the Stochastic Cortical Self-Reconstruction (SCSR), a novel method that leverages deep learning to reconstruct cortical thickness maps at the vertex level without needing additional subject information. Trained on over 25,000 healthy individuals, SCSR generates highly individualized cortical reconstructions that can detect subtle thickness deviations. Our evaluations on independent test sets demonstrated that SCSR achieved significantly lower reconstruction errors and identified atrophy patterns that enabled better disease discrimination than established methods. It also hints at cortical thinning in preterm infants that went undetected by existing models, showcasing its versatility. Finally, SCSR excelled in mapping highly resolved cortical deviations of dementia patients from clinical data, highlighting its potential for supporting diagnosis in clinical practice.