Denoising Diffusion Models for Anomaly Localization in Medical Images

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.

Modeling the Neonatal Brain Development Using Implicit Neural Representations

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.

Denoising Diffusion Models for 3D Healthy Brain Tissue Inpainting

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.

Binary Noise for Binary Tasks: Masked Bernoulli Diffusion for Unsupervised Anomaly Detection

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.

WDM: 3D Wavelet Diffusion Models for High-Resolution Medical Image Synthesis

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 diffusion models to high resolutions and can be trained on a single 40 GB GPU. Experimental results on BraTS and LIDC-IDRI unconditional image generation at a resolution of $128 \times 128 \times 128$ show state-of-the-art image fidelity (FID) and sample diversity (MS-SSIM) scores compared to GANs, Diffusion Models, and Latent Diffusion Models. Our proposed method is the only one capable of generating high-quality images at a resolution of $256 \times 256 \times 256$.

Denoising Diffusion Models for Inpainting of Healthy Brain Tissue

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.

Generative AI for Medical Imaging: extending the MONAI Framework

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.

Diffusion Models for Memory-efficient Processing of 3D Medical Images

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.

Diffusion Models for Contrast Harmonization of Magnetic Resonance Images

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.

Point Cloud Diffusion Models for Automatic Implant Generation

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.