Florentin Bieder

Julia Wolleb, Florentin Bieder, Robin Sandkühler et al.

In medical applications, weakly supervised anomaly detection methods are of great interest, as only image-level annotations are required for training. Current anomaly detection methods mainly rely on generative adversarial networks or autoencoder models. Those models are often complicated to train or have difficulties to preserve fine details in the image. We present a novel weakly supervised anomaly detection method based on denoising diffusion implicit models. We combine the deterministic iterative noising and denoising scheme with classifier guidance for image-to-image translation between diseased and healthy subjects. Our method generates very detailed anomaly maps without the need for a complex training procedure. We evaluate our method on the BRATS2020 dataset for brain tumor detection and the CheXpert dataset for detecting pleural effusions.

Florentin Bieder, Julia Wolleb, Alicia Durrer et al.

Denoising diffusion models have recently achieved state-of-the-art performance in many image-generation tasks. They do, however, require a large amount of computational resources. This limits their application to medical tasks, where we often deal with large 3D volumes, like high-resolution three-dimensional data. In this work, we present a number of different ways to reduce the resource consumption for 3D diffusion models and apply them to a dataset of 3D images. The main contribution of this paper is the memory-efficient patch-based diffusion model \textit{PatchDDM}, which can be applied to the total volume during inference while the training is performed only on patches. While the proposed diffusion model can be applied to any image generation tasks, we evaluate the method on the tumor segmentation task of the BraTS2020 dataset and demonstrate that we can generate meaningful three-dimensional segmentations.

Julia Wolleb, Robin Sandkühler, Florentin Bieder et al.

Recently, diffusion models were applied to a wide range of image analysis tasks. We build on a method for image-to-image translation using denoising diffusion implicit models and include a regression problem and a segmentation problem for guiding the image generation to the desired output. The main advantage of our approach is that the guidance during the denoising process is done by an external gradient. Consequently, the diffusion model does not need to be retrained for the different tasks on the same dataset. We apply our method to simulate the aging process on facial photos using a regression task, as well as on a brain magnetic resonance (MR) imaging dataset for the simulation of brain tumor growth. Furthermore, we use a segmentation model to inpaint tumors at the desired location in healthy slices of brain MR images. We achieve convincing results for all problems.

Paul Friedrich, Julia Wolleb, Florentin Bieder et al.

Advances in 3D printing of biocompatible materials make patient-specific implants increasingly popular. The design of these implants is, however, still a tedious and largely manual process. Existing approaches to automate implant generation are mainly based on 3D U-Net architectures on downsampled or patch-wise data, which can result in a loss of detail or contextual information. Following the recent success of Diffusion Probabilistic Models, we propose a novel approach for implant generation based on a combination of 3D point cloud diffusion models and voxelization networks. Due to the stochastic sampling process in our diffusion model, we can propose an ensemble of different implants per defect, from which the physicians can choose the most suitable one. We evaluate our method on the SkullBreak and SkullFix datasets, generating high-quality implants and achieving competitive evaluation scores.

Alicia Durrer, Julia Wolleb, Florentin Bieder et al.

Magnetic resonance (MR) images from multiple sources often show differences in image contrast related to acquisition settings or the used scanner type. For long-term studies, longitudinal comparability is essential but can be impaired by these contrast differences, leading to biased results when using automated evaluation tools. This study presents a diffusion model-based approach for contrast harmonization. We use a data set consisting of scans of 18 Multiple Sclerosis patients and 22 healthy controls. Each subject was scanned in two MR scanners of different magnetic field strengths (1.5 T and 3 T), resulting in a paired data set that shows scanner-inherent differences. We map images from the source contrast to the target contrast for both directions, from 3 T to 1.5 T and from 1.5 T to 3 T. As we only want to change the contrast, not the anatomical information, our method uses the original image to guide the image-to-image translation process by adding structural information. The aim is that the mapped scans display increased comparability with scans of the target contrast for downstream tasks. We evaluate this method for the task of segmentation of cerebrospinal fluid, grey matter and white matter. Our method achieves good and consistent results for both directions of the mapping.

Florentin Bieder, Julia Wolleb, Robin Sandkühler et al.

In recent years, anomaly detection has become an essential field in medical image analysis. Most current anomaly detection methods for medical images are based on image reconstruction. In this work, we propose a novel anomaly detection approach based on coordinate regression. Our method estimates the position of patches within a volume, and is trained only on data of healthy subjects. During inference, we can detect and localize anomalies by considering the error of the position estimate of a given patch. We apply our method to 3D CT volumes and evaluate it on patients with intracranial haemorrhages and cranial fractures. The results show that our method performs well in detecting these anomalies. Furthermore, we show that our method requires less memory than comparable approaches that involve image reconstruction. This is highly relevant for processing large 3D volumes, for instance, CT or MRI scans.

Julian McGinnis, Florian A. Hölzl, Suprosanna Shit et al.

Implicit Neural Representations (INRs) based on vanilla Multi-Layer Perceptrons (MLPs) are widely believed to be incapable of representing high-frequency content. This has directed research efforts towards architectural interventions, such as coordinate embeddings or specialized activation functions, to represent high-frequency signals. In this paper, we challenge the notion that the low-frequency bias of vanilla MLPs is an intrinsic, architectural limitation to learn high-frequency content, but instead a symptom of stable rank degradation during training. We empirically demonstrate that regulating the network's rank during training substantially improves the fidelity of the learned signal, rendering even simple MLP architectures expressive. Extensive experiments show that using optimizers like Muon, with high-rank, near-orthogonal updates, consistently enhances INR architectures even beyond simple ReLU MLPs. These substantial improvements hold across a diverse range of domains, including natural and medical images, and novel view synthesis, with up to 9 dB PSNR improvements over the previous state-of-the-art. Our project page, which includes code and experimental results, is available at: (https://muon-inrs.github.io).

Florentin Bieder, Paul Friedrich, Hélène Corbaz et al.

The human brain undergoes rapid development during the third trimester of pregnancy. In this work, we model the neonatal development of the infant brain in this age range. As a basis, we use MR images of preterm- and term-birth neonates from the developing human connectome project (dHCP). We propose a neural network, specifically an implicit neural representation (INR), to predict 2D- and 3D images of varying time points. In order to model a subject-specific development process, it is necessary to disentangle the age from the subjects' identity in the latent space of the INR. We propose two methods, Subject Specific Latent Vectors (SSL) and Stochastic Global Latent Augmentation (SGLA), enabling this disentanglement. We perform an analysis of the results and compare our proposed model to an age-conditioned denoising diffusion model as a baseline. We also show that our method can be applied in a memory-efficient way, which is especially important for 3D data.

Julia Wolleb, Florentin Bieder, Paul Friedrich et al.

The high performance of denoising diffusion models for image generation has paved the way for their application in unsupervised medical anomaly detection. As diffusion-based methods require a lot of GPU memory and have long sampling times, we present a novel and fast unsupervised anomaly detection approach based on latent Bernoulli diffusion models. We first apply an autoencoder to compress the input images into a binary latent representation. Next, a diffusion model that follows a Bernoulli noise schedule is employed to this latent space and trained to restore binary latent representations from perturbed ones. The binary nature of this diffusion model allows us to identify entries in the latent space that have a high probability of flipping their binary code during the denoising process, which indicates out-of-distribution data. We propose a masking algorithm based on these probabilities, which improves the anomaly detection scores. We achieve state-of-the-art performance compared to other diffusion-based unsupervised anomaly detection algorithms while significantly reducing sampling time and memory consumption. The code is available at https://github.com/JuliaWolleb/Anomaly_berdiff.

Paul Friedrich, Florentin Bieder, Florian M. Thieringer et al.

Facial feminization surgery (FFS) is a key component of gender affirmation for transgender and gender diverse patients, aiming to reshape craniofacial structures toward a female morphology. Current surgical planning procedures largely rely on subjective clinical assessment, lacking quantitative and reproducible anatomical guidance. We therefore propose AutoFFS, a novel data-driven framework that generates counterfactual skull morphologies through adversarial free-form deformations. Our method performs a deformation-based targeted adversarial attack on an ensemble of pre-trained binary sex classifiers that learned sexual dimorphism, effectively transforming individual skull shapes toward the target sex. The generated counterfactual skull morphologies provide a quantitative foundation for preoperative planning in FFS, driving advances in this largely overlooked patient group. We validate our approach through classifier-based evaluation and a human perceptual study, confirming that the generated morphologies exhibit target sex characteristics.

Alicia Durrer, Florentin Bieder, Paul Friedrich et al.

Healthy tissue inpainting has significant applications, including the generation of pseudo-healthy baselines for tumor growth models and the facilitation of image registration. In previous editions of the BraTS Local Synthesis of Healthy Brain Tissue via Inpainting Challenge, denoising diffusion probabilistic models (DDPMs) demonstrated qualitatively convincing results but suffered from low sampling speed. To mitigate this limitation, we adapted a 2D image generation approach, combining DDPMs with generative adversarial networks (GANs) and employing a variance-preserving noise schedule, for the task of 3D inpainting. Our experiments showed that the variance-preserving noise schedule and the selected reconstruction losses can be effectively utilized for high-quality 3D inpainting in a few time steps without requiring adversarial training. We applied our findings to a different architecture, a 3D wavelet diffusion model (WDM3D) that does not include a GAN component. The resulting model, denoted as fastWDM3D, obtained a SSIM of 0.8571, a MSE of 0.0079, and a PSNR of 22.26 on the BraTS inpainting test set. Remarkably, it achieved these scores using only two time steps, completing the 3D inpainting process in 1.81 s per image. When compared to other DDPMs used for healthy brain tissue inpainting, our model is up to 800 x faster while still achieving superior performance metrics. Our proposed method, fastWDM3D, represents a promising approach for fast and accurate healthy tissue inpainting. Our code is available at https://github.com/AliciaDurrer/fastWDM3D.

Hélène Corbaz, Anh Nguyen, Victor Schulze-Zachau et al.

Patients undergoing a mechanical thrombectomy procedure usually have a multi-detector CT (MDCT) scan before and after the intervention. The image quality of the flat panel detector CT (FDCT) present in the intervention room is generally much lower than that of a MDCT due to significant artifacts. However, using only FDCT images could improve patient management as the patient would not need to be moved to the MDCT room. Several studies have evaluated the potential use of FDCT imaging alone and the time that could be saved by acquiring the images before and/or after the intervention only with the FDCT. This study proposes using a denoising diffusion probabilistic model (DDPM) to improve the image quality of FDCT scans, making them comparable to MDCT scans. Clinicans evaluated FDCT, MDCT, and our model's predictions for diagnostic purposes using a questionnaire. The DDPM eliminated most artifacts and improved anatomical visibility without reducing bleeding detection, provided that the input FDCT image quality is not too low. Our code can be found on github.

Julia Wolleb, Florentin Bieder, Paul Friedrich et al.

Ultrasound is widely used in clinical care, yet standard deep learning methods often struggle with full video analysis due to non-standardized acquisition and operator bias. We offer a new perspective on ultrasound video analysis through implicit neural representations (INRs). We build on Functa, an INR framework in which each image is represented by a modulation vector that conditions a shared neural network. However, its extension to the temporal domain of medical videos remains unexplored. To address this gap, we propose VidFuncta, a novel framework that leverages Functa to encode variable-length ultrasound videos into compact, time-resolved representations. VidFuncta disentangles each video into a static video-specific vector and a sequence of time-dependent modulation vectors, capturing both temporal dynamics and dataset-level redundancies. Our method outperforms 2D and 3D baselines on video reconstruction and enables downstream tasks to directly operate on the learned 1D modulation vectors. We validate VidFuncta on three public ultrasound video datasets -- cardiac, lung, and breast -- and evaluate its downstream performance on ejection fraction prediction, B-line detection, and breast lesion classification. These results highlight the potential of VidFuncta as a generalizable and efficient representation framework for ultrasound videos. Our code is publicly available under https://github.com/JuliaWolleb/VidFuncta_public.

Paul Friedrich, Florentin Bieder, Julian McGinnis et al.

Research in medical imaging primarily focuses on discrete data representations that poorly scale with grid resolution and fail to capture the often continuous nature of the underlying signal. Neural Fields (NFs) offer a powerful alternative by modeling data as continuous functions. While single-instance NFs have successfully been applied in medical contexts, extending them to large-scale medical datasets remains an open challenge. We therefore introduce MedFuncta, a unified framework for large-scale NF training on diverse medical signals. Building on Functa, our approach encodes data into a unified representation, namely a 1D latent vector, that modulates a shared, meta-learned NF, enabling generalization across a dataset. We revisit common design choices, introducing a non-constant frequency parameter $ω$ in widely used SIREN activations, and establish a connection between this $ω$-schedule and layer-wise learning rates, relating our findings to recent work in theoretical learning dynamics. We additionally introduce a scalable meta-learning strategy for shared network learning that employs sparse supervision during training, thereby reducing memory consumption and computational overhead while maintaining competitive performance. Finally, we evaluate MedFuncta across a diverse range of medical datasets and show how to solve relevant downstream tasks on our neural data representation. To promote further research in this direction, we release our code, model weights and the first large-scale dataset - MedNF - containing > 500 k latent vectors for multi-instance medical NFs.

Paul Friedrich, Julia Wolleb, Florentin Bieder et al.

Due to the three-dimensional nature of CT- or MR-scans, generative modeling of medical images is a particularly challenging task. Existing approaches mostly apply patch-wise, slice-wise, or cascaded generation techniques to fit the high-dimensional data into the limited GPU memory. However, these approaches may introduce artifacts and potentially restrict the model's applicability for certain downstream tasks. This work presents WDM, a wavelet-based medical image synthesis framework that applies a diffusion model on wavelet decomposed images. The presented approach is a simple yet effective way of scaling 3D diffusion models to high resolutions and can be trained on a single \SI{40}{\giga\byte} GPU. Experimental results on BraTS and LIDC-IDRI unconditional image generation at a resolution of $128 \times 128 \times 128$ demonstrate state-of-the-art image fidelity (FID) and sample diversity (MS-SSIM) scores compared to recent GANs, Diffusion Models, and Latent Diffusion Models. Our proposed method is the only one capable of generating high-quality images at a resolution of $256 \times 256 \times 256$, outperforming all comparing methods.

Alicia Durrer, Julia Wolleb, Florentin Bieder et al.

Monitoring diseases that affect the brain's structural integrity requires automated analysis of magnetic resonance (MR) images, e.g., for the evaluation of volumetric changes. However, many of the evaluation tools are optimized for analyzing healthy tissue. To enable the evaluation of scans containing pathological tissue, it is therefore required to restore healthy tissue in the pathological areas. In this work, we explore and extend denoising diffusion models for consistent inpainting of healthy 3D brain tissue. We modify state-of-the-art 2D, pseudo-3D, and 3D methods working in the image space, as well as 3D latent and 3D wavelet diffusion models, and train them to synthesize healthy brain tissue. Our evaluation shows that the pseudo-3D model performs best regarding the structural-similarity index, peak signal-to-noise ratio, and mean squared error. To emphasize the clinical relevance, we fine-tune this model on data containing synthetic MS lesions and evaluate it on a downstream brain tissue segmentation task, whereby it outperforms the established FMRIB Software Library (FSL) lesion-filling method.

Madina Kojanazarova, Florentin Bieder, Robin Sandkühler et al.

Soft tissue simulation in virtual environments is becoming increasingly important for medical applications. However, the high deformability of soft tissue poses significant challenges. Existing methods rely on segmentation, meshing and estimation of stiffness properties of tissues. In addition, the integration of haptic feedback requires precise force estimation to enable a more immersive experience. We introduce a novel data-driven model, a conditional graph neural network (cGNN) to tackle this complexity. Our model takes surface points and the location of applied forces, and is specifically designed to predict the deformation of the points and the forces exerted on them. We trained our model on experimentally collected surface tracking data of a soft tissue phantom and used transfer learning to overcome the data scarcity by initially training it with mass-spring simulations and fine-tuning it with the experimental data. This approach improves the generalisation capability of the model and enables accurate predictions of tissue deformations and corresponding interaction forces. The results demonstrate that the model can predict deformations with a distance error of 0.35$\pm$0.03 mm for deformations up to 30 mm and the force with an absolute error of 0.37$\pm$0.05 N for forces up to 7.5 N. Our data-driven approach presents a promising solution to the intricate challenge of simulating soft tissues within virtual environments. Beyond its applicability in medical simulations, this approach holds the potential to benefit various fields where realistic soft tissue simulations are required.

Susanne Schaub, Florentin Bieder, Matheus L. Oliveira et al.

Cone-beam computed tomography (CBCT) is a widely used 3D imaging technique in dentistry, offering high-resolution images while minimising radiation exposure for patients. However, CBCT is highly susceptible to artefacts arising from high-density objects such as dental implants, which can compromise image quality and diagnostic accuracy. To reduce artefacts, implant inpainting in the sequence of projections plays a crucial role in many artefact reduction approaches. Recently, diffusion models have achieved state-of-the-art results in image generation and have widely been applied to image inpainting tasks. However, to our knowledge, existing diffusion-based methods for implant inpainting operate on independent 2D projections. This approach neglects the correlations among individual projections, resulting in inconsistencies in the reconstructed images. To address this, we propose a 3D dental implant inpainting approach based on perpendicular score-based diffusion models, each trained in two different planes and operating in the projection domain. The 3D distribution of the projection series is modelled by combining the two 2D score-based diffusion models in the sampling scheme. Our results demonstrate the method's effectiveness in producing high-quality, artefact-reduced 3D CBCT images, making it a promising solution for improving clinical imaging.

Vincent Ochs, Florentin Bieder, Sidaty el Hadramy et al.

Tabular data builds the basis for a wide range of applications, yet real-world datasets are frequently incomplete due to collection errors, privacy restrictions, or sensor failures. As missing values degrade the performance or hinder the applicability of downstream models, and while simple imputing strategies tend to introduce bias or distort the underlying data distribution, we require imputers that provide high-quality imputations, are robust across dataset sizes and yield fast inference. We therefore introduce TabINR, an auto-decoder based Implicit Neural Representation (INR) framework that models tables as neural functions. Building on recent advances in generalizable INRs, we introduce learnable row and feature embeddings that effectively deal with the discrete structure of tabular data and can be inferred from partial observations, enabling instance adaptive imputations without modifying the trained model. We evaluate our framework across a diverse range of twelve real-world datasets and multiple missingness mechanisms, demonstrating consistently strong imputation accuracy, mostly matching or outperforming classical (KNN, MICE, MissForest) and deep learning based models (GAIN, ReMasker), with the clearest gains on high-dimensional datasets.

Julia Wolleb, Robin Sandkühler, Florentin Bieder et al.

Diffusion models have shown impressive performance for generative modelling of images. In this paper, we present a novel semantic segmentation method based on diffusion models. By modifying the training and sampling scheme, we show that diffusion models can perform lesion segmentation of medical images. To generate an image specific segmentation, we train the model on the ground truth segmentation, and use the image as a prior during training and in every step during the sampling process. With the given stochastic sampling process, we can generate a distribution of segmentation masks. This property allows us to compute pixel-wise uncertainty maps of the segmentation, and allows an implicit ensemble of segmentations that increases the segmentation performance. We evaluate our method on the BRATS2020 dataset for brain tumor segmentation. Compared to state-of-the-art segmentation models, our approach yields good segmentation results and, additionally, detailed uncertainty maps.

Julia Wolleb, Robin Sandkühler, Florentin Bieder et al.

The limited availability of large image datasets, mainly due to data privacy and differences in acquisition protocols or hardware, is a significant issue in the development of accurate and generalizable machine learning methods in medicine. This is especially the case for Magnetic Resonance (MR) images, where different MR scanners introduce a bias that limits the performance of a machine learning model. We present a novel method that learns to ignore the scanner-related features present in MR images, by introducing specific additional constraints on the latent space. We focus on a real-world classification scenario, where only a small dataset provides images of all classes. Our method \textit{Learn to Ignore (L2I)} outperforms state-of-the-art domain adaptation methods on a multi-site MR dataset for a classification task between multiple sclerosis patients and healthy controls.

Florentin Bieder, Robin Sandkühler, Philippe C. Cattin

Max- and average-pooling are the most popular pooling methods for downsampling in convolutional neural networks. In this paper, we compare different pooling methods that generalize both max- and average-pooling. Furthermore, we propose another method based on a smooth approximation of the maximum function and put it into context with related methods. For the comparison, we use a VGG16 image classification network and train it on a large dataset of natural high-resolution images (Google Open Images v5). The results show that none of the more sophisticated methods perform significantly better in this classification task than standard max- or average-pooling.