Paul Friedrich

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.

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.

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.

Simone Sarrocco, Philippe C. Cattin, Peter M. Maloca et al.

Purpose: To evaluate deep learning (DL) models for enhancing vitreous optical coherence tomography (OCT) image quality and reducing acquisition time. Methods: Conditional Denoising Diffusion Probabilistic Models (cDDPMs), Brownian Bridge Diffusion Models (BBDMs), U-Net, Pix2Pix, and Vector-Quantised Generative Adversarial Network (VQ-GAN) were used to generate high-quality spectral-domain (SD) vitreous OCT images. Inputs were SD ART10 images, and outputs were compared to pseudoART100 images obtained by averaging ten ART10 images per eye location. Model performance was assessed using image quality metrics and Visual Turing Tests, where ophthalmologists ranked generated images and evaluated anatomical fidelity. The best model's performance was further tested within the manually segmented vitreous on newly acquired data. Results: U-Net achieved the highest Peak Signal-to-Noise Ratio (PSNR: 30.230) and Structural Similarity Index Measure (SSIM: 0.820), followed by cDDPM. For Learned Perceptual Image Patch Similarity (LPIPS), Pix2Pix (0.697) and cDDPM (0.753) performed best. In the first Visual Turing Test, cDDPM ranked highest (3.07); in the second (best model only), cDDPM achieved a 32.9% fool rate and 85.7% anatomical preservation. On newly acquired data, cDDPM generated vitreous regions more similar in PSNR to the ART100 reference than true ART1 or ART10 B-scans and achieved higher PSNR on whole images when conditioned on ART1 than ART10. Conclusions: Results reveal discrepancies between quantitative metrics and clinical evaluation, highlighting the need for combined assessment. cDDPM showed strong potential for generating clinically meaningful vitreous OCT images while reducing acquisition time fourfold. Translational Relevance: cDDPMs show promise for clinical integration, supporting faster, higher-quality vitreous imaging. Dataset and code will be made publicly available.

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.

Paul Friedrich, Yannik Frisch, Philippe C. Cattin

Deep generative modeling has emerged as a powerful tool for synthesizing realistic medical images, driving advances in medical image analysis, disease diagnosis, and treatment planning. This chapter explores various deep generative models for 3D medical image synthesis, with a focus on Variational Autoencoders (VAEs), Generative Adversarial Networks (GANs), and Denoising Diffusion Models (DDMs). We discuss the fundamental principles, recent advances, as well as strengths and weaknesses of these models and examine their applications in clinically relevant problems, including unconditional and conditional generation tasks like image-to-image translation and image reconstruction. We additionally review commonly used evaluation metrics for assessing image fidelity, diversity, utility, and privacy and provide an overview of current challenges in the field.

Paul Friedrich, Alicia Durrer, Julia Wolleb et al.

This paper contributes to the "BraTS 2024 Brain MR Image Synthesis Challenge" and presents a conditional Wavelet Diffusion Model (cWDM) for directly solving a paired image-to-image translation task on high-resolution volumes. While deep learning-based brain tumor segmentation models have demonstrated clear clinical utility, they typically require MR scans from various modalities (T1, T1ce, T2, FLAIR) as input. However, due to time constraints or imaging artifacts, some of these modalities may be missing, hindering the application of well-performing segmentation algorithms in clinical routine. To address this issue, we propose a method that synthesizes one missing modality image conditioned on three available images, enabling the application of downstream segmentation models. We treat this paired image-to-image translation task as a conditional generation problem and solve it by combining a Wavelet Diffusion Model for high-resolution 3D image synthesis with a simple conditioning strategy. This approach allows us to directly apply our model to full-resolution volumes, avoiding artifacts caused by slice- or patch-wise data processing. While this work focuses on a specific application, the presented method can be applied to all kinds of paired image-to-image translation problems, such as CT $\leftrightarrow$ MR and MR $\leftrightarrow$ PET translation, or mask-conditioned anatomically guided image generation.

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.

Maël Macuglia, Paul Friedrich, Giorgia Ramponi

Deploying reinforcement learning (RL) in robotics, industry, and health care is blocked by two obstacles: the difficulty of specifying accurate rewards and the risk of unsafe, data-hungry exploration. We address this by proposing a two-stage framework that first learns a safe initial policy from a reward-free dataset of expert demonstrations, then fine-tunes it online using preference-based human feedback. We provide the first principled analysis of this offline-to-online approach and introduce BRIDGE, a unified algorithm that integrates both signals via an uncertainty-weighted objective. We derive regret bounds that shrink with the number of offline demonstrations, explicitly connecting the quantity of offline data to online sample efficiency. We validate BRIDGE in discrete and continuous control MuJoCo environments, showing it achieves lower regret than both standalone behavioral cloning and online preference-based RL. Our work establishes a theoretical foundation for designing more sample-efficient interactive agents.

Michael Wehrli, Alicia Durrer, Paul Friedrich et al.

To treat Trochlear Dysplasia (TD), current approaches rely mainly on low-resolution clinical Magnetic Resonance (MR) scans and surgical intuition. The surgeries are planned based on surgeons experience, have limited adoption of minimally invasive techniques, and lead to inconsistent outcomes. We propose a pipeline that generates super-resolved, patient-specific 3D pseudo-healthy target morphologies from conventional clinical MR scans. First, we compute an isotropic super-resolved MR volume using an Implicit Neural Representation (INR). Next, we segment femur, tibia, patella, and fibula with a multi-label custom-trained network. Finally, we train a Wavelet Diffusion Model (WDM) to generate pseudo-healthy target morphologies of the trochlear region. In contrast to prior work producing pseudo-healthy low-resolution 3D MR images, our approach enables the generation of sub-millimeter resolved 3D shapes compatible for pre- and intraoperative use. These can serve as preoperative blueprints for reshaping the femoral groove while preserving the native patella articulation. Furthermore, and in contrast to other work, we do not require a CT for our pipeline - reducing the amount of radiation. We evaluated our approach on 25 TD patients and could show that our target morphologies significantly improve the sulcus angle (SA) and trochlear groove depth (TGD). The code and interactive visualization are available at https://wehrlimi.github.io/sr-3d-planning/.