Chinmay Prabhakar

Chinmay Prabhakar, Hongwei Bran Li, Jiancheng Yang et al.

Self-supervised learning has attracted increasing attention as it learns data-driven representation from data without annotations. Vision transformer-based autoencoder (ViT-AE) by He et al. (2021) is a recent self-supervised learning technique that employs a patch-masking strategy to learn a meaningful latent space. In this paper, we focus on improving ViT-AE (nicknamed ViT-AE++) for a more effective representation of 2D and 3D medical images. We propose two new loss functions to enhance the representation during training. The first loss term aims to improve self-reconstruction by considering the structured dependencies and indirectly improving the representation. The second loss term leverages contrastive loss to optimize the representation from two randomly masked views directly. We extended ViT-AE++ to a 3D fashion for volumetric medical images as an independent contribution. We extensively evaluate ViT-AE++ on both natural images and medical images, demonstrating consistent improvement over vanilla ViT-AE and its superiority over other contrastive learning approaches. Codes are here: https://github.com/chinmay5/vit_ae_plus_plus.git.

Chinmay Prabhakar, Hongwei Bran Li, Johannes C. Paetzold et al.

Multiple Sclerosis (MS) is a severe neurological disease characterized by inflammatory lesions in the central nervous system. Hence, predicting inflammatory disease activity is crucial for disease assessment and treatment. However, MS lesions can occur throughout the brain and vary in shape, size and total count among patients. The high variance in lesion load and locations makes it challenging for machine learning methods to learn a globally effective representation of whole-brain MRI scans to assess and predict disease. Technically it is non-trivial to incorporate essential biomarkers such as lesion load or spatial proximity. Our work represents the first attempt to utilize graph neural networks (GNN) to aggregate these biomarkers for a novel global representation. We propose a two-stage MS inflammatory disease activity prediction approach. First, a 3D segmentation network detects lesions, and a self-supervised algorithm extracts their image features. Second, the detected lesions are used to build a patient graph. The lesions act as nodes in the graph and are initialized with image features extracted in the first stage. Finally, the lesions are connected based on their spatial proximity and the inflammatory disease activity prediction is formulated as a graph classification task. Furthermore, we propose a self-pruning strategy to auto-select the most critical lesions for prediction. Our proposed method outperforms the existing baseline by a large margin (AUCs of 0.67 vs. 0.61 and 0.66 vs. 0.60 for one-year and two-year inflammatory disease activity, respectively). Finally, our proposed method enjoys inherent explainability by assigning an importance score to each lesion for the overall prediction. Code is available at https://github.com/chinmay5/ms_ida.git

Aswathi Varma, Suprosanna Shit, Chinmay Prabhakar et al.

Vision Transformers (ViTs) have emerged as the state-of-the-art architecture in representation learning, leveraging self-attention mechanisms to excel in various tasks. ViTs split images into fixed-size patches, constraining them to a predefined size and necessitating pre-processing steps like resizing, padding, or cropping. This poses challenges in medical imaging, particularly with irregularly shaped structures like tumors. A fixed bounding box crop size produces input images with highly variable foreground-to-background ratios. Resizing medical images can degrade information and introduce artefacts, impacting diagnosis. Hence, tailoring variable-sized crops to regions of interest can enhance feature representation capabilities. Moreover, large images are computationally expensive, and smaller sizes risk information loss, presenting a computation-accuracy tradeoff. We propose VariViT, an improved ViT model crafted to handle variable image sizes while maintaining a consistent patch size. VariViT employs a novel positional embedding resizing scheme for a variable number of patches. We also implement a new batching strategy within VariViT to reduce computational complexity, resulting in faster training and inference times. In our evaluations on two 3D brain MRI datasets, VariViT surpasses vanilla ViTs and ResNet in glioma genotype prediction and brain tumor classification. It achieves F1-scores of 75.5% and 76.3%, respectively, learning more discriminative features. Our proposed batching strategy reduces computation time by up to 30% compared to conventional architectures. These findings underscore the efficacy of VariViT in image representation learning. Our code can be found here: https://github.com/Aswathi-Varma/varivit

Bastian Wittmann, Johannes C. Paetzold, Chinmay Prabhakar et al.

Link prediction algorithms aim to infer the existence of connections (or links) between nodes in network-structured data and are typically applied to refine the connectivity among nodes. In this work, we focus on link prediction for flow-driven spatial networks, which are embedded in a Euclidean space and relate to physical exchange and transportation processes (e.g., blood flow in vessels or traffic flow in road networks). To this end, we propose the Graph Attentive Vectors (GAV) link prediction framework. GAV models simplified dynamics of physical flow in spatial networks via an attentive, neighborhood-aware message-passing paradigm, updating vector embeddings in a constrained manner. We evaluate GAV on eight flow-driven spatial networks given by whole-brain vessel graphs and road networks. GAV demonstrates superior performances across all datasets and metrics and outperformed the state-of-the-art on the ogbl-vessel benchmark at the time of submission by 12% (98.38 vs. 87.98 AUC). All code is publicly available on GitHub.

Hongwei Bran Li, Chinmay Prabhakar, Suprosanna Shit et al.

Quantifying the perceptual similarity of two images is a long-standing problem in low-level computer vision. The natural image domain commonly relies on supervised learning, e.g., a pre-trained VGG, to obtain a latent representation. However, due to domain shift, pre-trained models from the natural image domain might not apply to other image domains, such as medical imaging. Notably, in medical imaging, evaluating the perceptual similarity is exclusively performed by specialists trained extensively in diverse medical fields. Thus, medical imaging remains devoid of task-specific, objective perceptual measures. This work answers the question: Is it necessary to rely on supervised learning to obtain an effective representation that could measure perceptual similarity, or is self-supervision sufficient? To understand whether recent contrastive self-supervised representation (CSR) may come to the rescue, we start with natural images and systematically evaluate CSR as a metric across numerous contemporary architectures and tasks and compare them with existing methods. We find that in the natural image domain, CSR behaves on par with the supervised one on several perceptual tests as a metric, and in the medical domain, CSR better quantifies perceptual similarity concerning the experts' ratings. We also demonstrate that CSR can significantly improve image quality in two image synthesis tasks. Finally, our extensive results suggest that perceptuality is an emergent property of CSR, which can be adapted to many image domains without requiring annotations.

Chinmay Prabhakar, Suprosanna Shit, Fabio Musio et al.

Blood vessel networks, represented as 3D graphs, help predict disease biomarkers, simulate blood flow, and aid in synthetic image generation, relevant in both clinical and pre-clinical settings. However, generating realistic vessel graphs that correspond to an anatomy of interest is challenging. Previous methods aimed at generating vessel trees mostly in an autoregressive style and could not be applied to vessel graphs with cycles such as capillaries or specific anatomical structures such as the Circle of Willis. Addressing this gap, we introduce the first application of \textit{denoising diffusion models} in 3D vessel graph generation. Our contributions include a novel, two-stage generation method that sequentially denoises node coordinates and edges. We experiment with two real-world vessel datasets, consisting of microscopic capillaries and major cerebral vessels, and demonstrate the generalizability of our method for producing diverse, novel, and anatomically plausible vessel graphs.

Chinmay Prabhakar, Bastian Wittmann, Tamaz Amiranashvili et al.

Spatial graphs provide a lightweight and elegant representation of curvilinear anatomical structures such as blood vessels, lung airways, and neuronal networks. Accurately modeling these graphs is crucial in clinical and (bio-)medical research. However, the high spatial resolution of large networks drastically increases their complexity, resulting in significant computational challenges. In this work, we aim to tackle these challenges by proposing VesselTok, a framework that approaches spatially dense graphs from a parametric shape perspective to learn latent representations (tokens). VesselTok leverages centerline points with a pseudo radius to effectively encode tubular geometry. Specifically, we learn a novel latent representation conditioned on centerline points to encode neural implicit representations of vessel-like, tubular structures. We demonstrate VesselTok's performance across diverse anatomies, including lung airways, lung vessels, and brain vessels, highlighting its ability to robustly encode complex topologies. To prove the effectiveness of VesselTok's learnt latent representations, we show that they (i) generalize to unseen anatomies, (ii) support generative modeling of plausible anatomical graphs, and (iii) transfer effectively to downstream inverse problems, such as link prediction.

Chinmay Prabhakar, Bastian Wittmann, Paul Büschl et al.

Analyzing human vasculature and vessel-like, tubular structures, such as airways, is crucial for disease diagnosis and treatment. Current methods often rely on small sub-regions or simplified tree-like structures, rendering analysis of entire organ-level networks at clinical resolution computationally challenging. To this end, we propose VAEsselSparse, an efficient encoder-decoder model to obtain a meaningful yet compact representation of the entire organ-level vascular network at sub-millimeter resolution. VAEsselSparse leverages the inherent sparsity of 3D vascular structures via sparse convolutions and attention mechanisms, achieving substantial spatial compression rates of 8 x 8 x 8. We demonstrate superior reconstruction performance compared to dense counterparts and previous methods. Importantly, the resulting latent space retains clinically relevant discriminative features readily usable for classification tasks, such as aneurysm/stenosis or subvariants of the circle of Willis. Moreover, the compact latent space of VAEsselSparse serves as an effective representation for learning vessel-specific priors through generative models, enabling the synthesis of realistic vasculature.

Michal Balcerak, Suprosana Shit, Chinmay Prabhakar et al.

Energy-based models for discrete domains, such as graphs, explicitly capture relative likelihoods, naturally enabling composable probabilistic inference tasks like conditional generation or enforcing constraints at test-time. However, discrete energy-based models typically struggle with efficient and high-quality sampling, as off-support regions often contain spurious local minima, trapping samplers and causing training instabilities. This has historically resulted in a fidelity gap relative to discrete diffusion models. We introduce Graph Energy Matching (GEM), a generative framework for graphs that closes this fidelity gap. Motivated by the transport map optimization perspective of the Jordan-Kinderlehrer-Otto (JKO) scheme, GEM learns a permutation-invariant potential energy that simultaneously provides transport-aligned guidance from noise toward data and refines samples within regions of high data likelihood. Further, we introduce a sampling protocol that leverages an energy-based switch to seamlessly bridge: (i) rapid, gradient-guided transport toward high-probability regions to (ii) a mixing regime for exploration of the learned graph distribution. On molecular graph benchmarks, GEM matches or exceeds strong discrete diffusion baselines. Beyond sample quality, explicit modeling of relative likelihood enables targeted exploration at inference time, facilitating compositional generation, property-constrained sampling, and geodesic interpolation between graphs.

Yuan Lin, Murong Xu, Marc Hölle et al.

Widely adopted medical image segmentation methods, although efficient, are primarily deterministic and remain poorly amenable to natural language prompts. Thus, they lack the capability to estimate multiple proposals, human interaction, and cross-modality adaptation. Recently, text-to-image diffusion models have shown potential to bridge the gap. However, training them from scratch requires a large dataset-a limitation for medical image segmentation. Furthermore, they are often limited to binary segmentation and cannot be conditioned on a natural language prompt. To this end, we propose a novel framework called ProGiDiff that leverages existing image generation models for medical image segmentation purposes. Specifically, we propose a ControlNet-style conditioning mechanism with a custom encoder, suitable for image conditioning, to steer a pre-trained diffusion model to output segmentation masks. It naturally extends to a multi-class setting simply by prompting the target organ. Our experiment on organ segmentation from CT images demonstrates strong performance compared to previous methods and could greatly benefit from an expert-in-the-loop setting to leverage multiple proposals. Importantly, we demonstrate that the learned conditioning mechanism can be easily transferred through low-rank, few-shot adaptation to segment MR images.

Ibrahim Ethem Hamamci, Sezgin Er, Anjany Sekuboyina et al.

GenerateCT, the first approach to generating 3D medical imaging conditioned on free-form medical text prompts, incorporates a text encoder and three key components: a novel causal vision transformer for encoding 3D CT volumes, a text-image transformer for aligning CT and text tokens, and a text-conditional super-resolution diffusion model. Without directly comparable methods in 3D medical imaging, we benchmarked GenerateCT against cutting-edge methods, demonstrating its superiority across all key metrics. Importantly, we evaluated GenerateCT's clinical applications in a multi-abnormality classification task. First, we established a baseline by training a multi-abnormality classifier on our real dataset. To further assess the model's generalization to external data and performance with unseen prompts in a zero-shot scenario, we employed an external set to train the classifier, setting an additional benchmark. We conducted two experiments in which we doubled the training datasets by synthesizing an equal number of volumes for each set using GenerateCT. The first experiment demonstrated an 11% improvement in the AP score when training the classifier jointly on real and generated volumes. The second experiment showed a 7% improvement when training on both real and generated volumes based on unseen prompts. Moreover, GenerateCT enables the scaling of synthetic training datasets to arbitrary sizes. As an example, we generated 100,000 3D CTs, fivefold the number in our real set, and trained the classifier exclusively on these synthetic CTs. Impressively, this classifier surpassed the performance of the one trained on all available real data by a margin of 8%. Last, domain experts evaluated the generated volumes, confirming a high degree of alignment with the text prompt. Access our code, model weights, training data, and generated data at https://github.com/ibrahimethemhamamci/GenerateCT

Johannes C. Paetzold, Julian McGinnis, Suprosanna Shit et al.

Biological neural networks define the brain function and intelligence of humans and other mammals, and form ultra-large, spatial, structured graphs. Their neuronal organization is closely interconnected with the spatial organization of the brain's microvasculature, which supplies oxygen to the neurons and builds a complementary spatial graph. This vasculature (or the vessel structure) plays an important role in neuroscience; for example, the organization of (and changes to) vessel structure can represent early signs of various pathologies, e.g. Alzheimer's disease or stroke. Recently, advances in tissue clearing have enabled whole brain imaging and segmentation of the entirety of the mouse brain's vasculature. Building on these advances in imaging, we are presenting an extendable dataset of whole-brain vessel graphs based on specific imaging protocols. Specifically, we extract vascular graphs using a refined graph extraction scheme leveraging the volume rendering engine Voreen and provide them in an accessible and adaptable form through the OGB and PyTorch Geometric dataloaders. Moreover, we benchmark numerous state-of-the-art graph learning algorithms on the biologically relevant tasks of vessel prediction and vessel classification using the introduced vessel graph dataset. Our work paves a path towards advancing graph learning research into the field of neuroscience. Complementarily, the presented dataset raises challenging graph learning research questions for the machine learning community, in terms of incorporating biological priors into learning algorithms, or in scaling these algorithms to handle sparse,spatial graphs with millions of nodes and edges. All datasets and code are available for download at https://github.com/jocpae/VesselGraph .

Kaiyuan Yang, Fabio Musio, Yihui Ma et al.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neurovascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two non-invasive angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited datasets with annotations on CoW anatomy, especially for CTA. Therefore, we organized the TopCoW challenge with the release of an annotated CoW dataset. The TopCoW dataset is the first public dataset with voxel-level annotations for 13 CoW vessel components, enabled by virtual reality technology. It is also the first large dataset using 200 pairs of MRA and CTA from the same patients. As part of the benchmark, we invited submissions worldwide and attracted over 250 registered participants from six continents. The submissions were evaluated on both internal and external test datasets of 226 scans from over five centers. The top performing teams achieved over 90% Dice scores at segmenting the CoW components, over 80% F1 scores at detecting key CoW components, and over 70% balanced accuracy at classifying CoW variants for nearly all test sets. The best algorithms also showed clinical potential in classifying fetal-type posterior cerebral artery and locating aneurysms with CoW anatomy. TopCoW demonstrated the utility and versatility of CoW segmentation algorithms for a wide range of downstream clinical applications with explainability. The annotated datasets and best performing algorithms have been released as public Zenodo records to foster further methodological development and clinical tool building.

Fabio Musio, Norman Juchler, Kaiyuan Yang et al.

The Circle of Willis (CoW) is a critical network of arteries in the brain, often implicated in cerebrovascular pathologies. Voxel-level segmentation is an important first step toward an automated CoW assessment, but a full quantitative analysis requires centerline representations. However, conventional skeletonization techniques often struggle to extract reliable centerlines due to the CoW's complex geometry, and publicly available centerline datasets remain scarce. To address these challenges, we used a thinning-based skeletonization algorithm to extract and curate centerline graphs and morphometric features from the TopCoW dataset, which includes 200 stroke patients, each imaged with MRA and CTA. The curated graphs were used to develop a baseline algorithm for centerline and feature extraction, combining U-Net-based skeletonization with A* graph connection. Performance was evaluated on a held-out test set, focusing on anatomical accuracy and feature robustness. Further, we used the extracted features to predict the frequency of fetal PCA variants, confirm theoretical bifurcation optimality relations, and detect subtle modality differences. The baseline algorithm consistently reconstructed graph topology with high accuracy (F1 = 1), and the average Euclidean node distance between reference and predicted graphs was below one voxel. Features such as segment radius, length, and bifurcation ratios showed strong robustness, with median relative errors below 5% and Pearson correlations above 0.95. Our results demonstrate the utility of learning-based skeletonization combined with graph connection for anatomically plausible centerline extraction. We emphasize the importance of going beyond simple voxel-based measures by evaluating anatomical accuracy and feature robustness. The dataset and baseline algorithm have been released to support further method development and clinical research.

Chinmay Prabhakar, Suprosanna Shit, Tamaz Amiranashvili et al.

3D spatial graphs play a crucial role in biological and clinical research by modeling anatomical networks such as blood vessels,neurons, and airways. However, generating 3D biological graphs while maintaining anatomical validity remains challenging, a key limitation of existing diffusion-based methods. In this work, we propose a novel 3D biological graph generation method that adheres to structural and semantic plausibility conditions. We achieve this by using a novel projection operator during sampling that stochastically fixes inconsistencies. Further, we adopt a superior edge-deletion-based noising procedure suitable for sparse biological graphs. Our method demonstrates superior performance on two real-world datasets, human circle of Willis and lung airways, compared to previous approaches. Importantly, we demonstrate that the generated samples significantly enhance downstream graph labeling performance. Furthermore, we show that our generative model is a reasonable out-of-the-box link predictior.

Hongwei Bran Li, Fernando Navarro, Ivan Ezhov et al.

Uncertainty in medical image segmentation tasks, especially inter-rater variability, arising from differences in interpretations and annotations by various experts, presents a significant challenge in achieving consistent and reliable image segmentation. This variability not only reflects the inherent complexity and subjective nature of medical image interpretation but also directly impacts the development and evaluation of automated segmentation algorithms. Accurately modeling and quantifying this variability is essential for enhancing the robustness and clinical applicability of these algorithms. We report the set-up and summarize the benchmark results of the Quantification of Uncertainties in Biomedical Image Quantification Challenge (QUBIQ), which was organized in conjunction with International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 and 2021. The challenge focuses on the uncertainty quantification of medical image segmentation which considers the omnipresence of inter-rater variability in imaging datasets. The large collection of images with multi-rater annotations features various modalities such as MRI and CT; various organs such as the brain, prostate, kidney, and pancreas; and different image dimensions 2D-vs-3D. A total of 24 teams submitted different solutions to the problem, combining various baseline models, Bayesian neural networks, and ensemble model techniques. The obtained results indicate the importance of the ensemble models, as well as the need for further research to develop efficient 3D methods for uncertainty quantification methods in 3D segmentation tasks.

Tamara T. Mueller, Johannes C. Paetzold, Chinmay Prabhakar et al.

Graph Neural Networks (GNNs) have established themselves as the state-of-the-art models for many machine learning applications such as the analysis of social networks, protein interactions and molecules. Several among these datasets contain privacy-sensitive data. Machine learning with differential privacy is a promising technique to allow deriving insight from sensitive data while offering formal guarantees of privacy protection. However, the differentially private training of GNNs has so far remained under-explored due to the challenges presented by the intrinsic structural connectivity of graphs. In this work, we introduce differential privacy for graph-level classification, one of the key applications of machine learning on graphs. Our method is applicable to deep learning on multi-graph datasets and relies on differentially private stochastic gradient descent (DP-SGD). We show results on a variety of synthetic and public datasets and evaluate the impact of different GNN architectures and training hyperparameters on model performance for differentially private graph classification. Finally, we apply explainability techniques to assess whether similar representations are learned in the private and non-private settings and establish robust baselines for future work in this area.