Julia Wolleb

Walter H. L. Pinaya, Mark S. Graham, Eric Kerfoot et al.

Recent advances in generative AI have brought incredible breakthroughs in several areas, including medical imaging. These generative models have tremendous potential not only to help safely share medical data via synthetic datasets but also to perform an array of diverse applications, such as anomaly detection, image-to-image translation, denoising, and MRI reconstruction. However, due to the complexity of these models, their implementation and reproducibility can be difficult. This complexity can hinder progress, act as a use barrier, and dissuade the comparison of new methods with existing works. In this study, we present MONAI Generative Models, a freely available open-source platform that allows researchers and developers to easily train, evaluate, and deploy generative models and related applications. Our platform reproduces state-of-art studies in a standardised way involving different architectures (such as diffusion models, autoregressive transformers, and GANs), and provides pre-trained models for the community. We have implemented these models in a generalisable fashion, illustrating that their results can be extended to 2D or 3D scenarios, including medical images with different modalities (like CT, MRI, and X-Ray data) and from different anatomical areas. Finally, we adopt a modular and extensible approach, ensuring long-term maintainability and the extension of current applications for future features.

Julia Wolleb, Cristiana Baloescu, Alicia Durrer et al.

Implicit neural representations (INRs) have emerged as a powerful framework for continuous image representation learning. In Functa-based approaches, each image is encoded as a latent modulation vector that conditions a shared INR, enabling strong reconstruction performance. However, the structure and interpretability of the corresponding latent spaces remain largely unexplored. In this work, we investigate the latent space of Functa-based models for ultrasound videos and propose Low-Rank-Modulated Functa (LRM-Functa), a novel architecture that enforces a low-rank adaptation of modulation vectors in the time-resolved latent space. When applied to cardiac ultrasound, the resulting latent space exhibits clearly structured periodic trajectories, facilitating visualization and interpretability of temporal patterns. The latent space can be traversed to sample novel frames, revealing smooth transitions along the cardiac cycle, and enabling direct readout of end-diastolic (ED) and end-systolic (ES) frames without additional model training. We show that LRM-Functa outperforms prior methods in unsupervised ED and ES frame detection, while compressing each video frame to as low as rank k=2 without sacrificing competitive downstream performance on ejection fraction prediction. Evaluations on out-of-distribution frame selection in a cardiac point-of-care dataset, as well as on lung ultrasound for B-line classification, demonstrate the generalizability of our approach. Overall, LRM-Functa provides a compact, interpretable, and generalizable framework for ultrasound video analysis. The code is available at https://github.com/JuliaWolleb/LRM_Functa.

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.

Eva Schnider, Julia Wolleb, Antal Huck et al.

Purpose: Automated distinct bone segmentation from CT scans is widely used in planning and navigation workflows. U-Net variants are known to provide excellent results in supervised semantic segmentation. However, in distinct bone segmentation from upper body CTs a large field of view and a computationally taxing 3D architecture are required. This leads to low-resolution results lacking detail or localisation errors due to missing spatial context when using high-resolution inputs. Methods: We propose to solve this problem by using end-to-end trainable segmentation networks that combine several 3D U-Nets working at different resolutions. Our approach, which extends and generalizes HookNet and MRN, captures spatial information at a lower resolution and skips the encoded information to the target network, which operates on smaller high-resolution inputs. We evaluated our proposed architecture against single resolution networks and performed an ablation study on information concatenation and the number of context networks. Results: Our proposed best network achieves a median DSC of 0.86 taken over all 125 segmented bone classes and reduces the confusion among similar-looking bones in different locations. These results outperform our previously published 3D U-Net baseline results on the task and distinct-bone segmentation results reported by other groups. Conclusion: The presented multi-resolution 3D U-Nets address current shortcomings in bone segmentation from upper-body CT scans by allowing for capturing a larger field of view while avoiding the cubic growth of the input pixels and intermediate computations that quickly outgrow the computational capacities in 3D. The approach thus improves the accuracy and efficiency of distinct bone segmentation from upper-body CT.

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.

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.

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.

Alicia Durrer, Philippe C. Cattin, Julia Wolleb

This paper is a contribution to the "BraTS 2023 Local Synthesis of Healthy Brain Tissue via Inpainting Challenge". The task of this challenge is to transform tumor tissue into healthy tissue in brain magnetic resonance (MR) images. This idea originates from the problem that MR images can be evaluated using automatic processing tools, however, many of these tools are optimized for the analysis of healthy tissue. By solving the given inpainting task, we enable the automatic analysis of images featuring lesions, and further downstream tasks. Our approach builds on denoising diffusion probabilistic models. We use a 2D model that is trained using slices in which healthy tissue was cropped out and is learned to be inpainted again. This allows us to use the ground truth healthy tissue during training. In the sampling stage, we replace the slices containing diseased tissue in the original 3D volume with the slices containing the healthy tissue inpainting. With our approach, we achieve comparable results to the competing methods. On the validation set our model achieves a mean SSIM of 0.7804, a PSNR of 20.3525 and a MSE of 0.0113. In future we plan to extend our 2D model to a 3D model, allowing to inpaint the region of interest as a whole without losing context information of neighboring slices.

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.

Cosmin I. Bercea, Philippe C. Cattin, Julia A. Schnabel et al.

This chapter explores anomaly localization in medical images using denoising diffusion models. After providing a brief methodological background of these models, including their application to image reconstruction and their conditioning using guidance mechanisms, we provide an overview of available datasets and evaluation metrics suitable for their application to anomaly localization in medical images. In this context, we discuss supervision schemes ranging from fully supervised segmentation to semi-supervised, weakly supervised, self-supervised, and unsupervised methods, and provide insights into the effectiveness and limitations of these approaches. Furthermore, we highlight open challenges in anomaly localization, including detection bias, domain shift, computational cost, and model interpretability. Our goal is to provide an overview of the current state of the art in the field, outline research gaps, and highlight the potential of diffusion models for robust anomaly localization in medical images.

Florian Kofler, Felix Meissen, Felix Steinbauer et al.

A myriad of algorithms for the automatic analysis of brain MR images is available to support clinicians in their decision-making. For brain tumor patients, the image acquisition time series typically starts with an already pathological scan. This poses problems, as many algorithms are designed to analyze healthy brains and provide no guarantee for images featuring lesions. Examples include, but are not limited to, algorithms for brain anatomy parcellation, tissue segmentation, and brain extraction. To solve this dilemma, we introduce the BraTS inpainting challenge. Here, the participants explore inpainting techniques to synthesize healthy brain scans from lesioned ones. The following manuscript contains the task formulation, dataset, and submission procedure. Later, it will be updated to summarize the findings of the challenge. The challenge is organized as part of the ASNR-BraTS MICCAI challenge.

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.

Julia Wolleb, Robin Sandkühler, Philippe C. Cattin

Anomaly detection and localization in medical images is a challenging task, especially when the anomaly exhibits a change of existing structures, e.g., brain atrophy or changes in the pleural space due to pleural effusions. In this work, we present a weakly supervised and detail-preserving method that is able to detect structural changes of existing anatomical structures. In contrast to standard anomaly detection methods, our method extracts information about the disease characteristics from two groups: a group of patients affected by the same disease and a healthy control group. Together with identity-preserving mechanisms, this enables our method to extract highly disease-specific characteristics for a more detailed detection of structural changes. We designed a specific synthetic data set to evaluate and compare our method against state-of-the-art anomaly detection methods. Finally, we show the performance of our method on chest X-ray images. Our method called DeScarGAN outperforms other anomaly detection methods on the synthetic data set and by visual inspection on the chest X-ray image data set.