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.

FMBench: Benchmarking Fairness in Multimodal Large Language Models on Medical Tasks

Advancements in Multimodal Large Language Models (MLLMs) have significantly improved medical task performance, such as Visual Question Answering (VQA) and Report Generation (RG). However, the fairness of these models across diverse demographic groups remains underexplored, despite its importance in healthcare. This oversight is partly due to the lack of demographic diversity in existing medical multimodal datasets, which complicates the evaluation of fairness. In response, we propose FMBench, the first benchmark designed to evaluate the fairness of MLLMs performance across diverse demographic attributes. FMBench has the following key features: 1: It includes four demographic attributes: race, ethnicity, language, and gender, across two tasks, VQA and RG, under zero-shot settings. 2: Our VQA task is free-form, enhancing real-world applicability and mitigating the biases associated with predefined choices. 3: We utilize both lexical metrics and LLM-based metrics, aligned with clinical evaluations, to assess models not only for linguistic accuracy but also from a clinical perspective. Furthermore, we introduce a new metric, Fairness-Aware Performance (FAP), to evaluate how fairly MLLMs perform across various demographic attributes. We thoroughly evaluate the performance and fairness of eight state-of-the-art open-source MLLMs, including both general and medical MLLMs, ranging from 7B to 26B parameters on the proposed benchmark. We aim for FMBench to assist the research community in refining model evaluation and driving future advancements in the field. All data and code will be released upon acceptance.

MedEdit: Counterfactual Diffusion-based Image Editing on Brain MRI

Denoising diffusion probabilistic models enable high-fidelity image synthesis and editing. In biomedicine, these models facilitate counterfactual image editing, producing pairs of images where one is edited to simulate hypothetical conditions. For example, they can model the progression of specific diseases, such as stroke lesions. However, current image editing techniques often fail to generate realistic biomedical counterfactuals, either by inadequately modeling indirect pathological effects like brain atrophy or by excessively altering the scan, which disrupts correspondence to the original images. Here, we propose MedEdit, a conditional diffusion model for medical image editing. MedEdit induces pathology in specific areas while balancing the modeling of disease effects and preserving the integrity of the original scan. We evaluated MedEdit on the Atlas v2.0 stroke dataset using Frechet Inception Distance and Dice scores, outperforming state-of-the-art diffusion-based methods such as Palette (by 45%) and SDEdit (by 61%). Additionally, clinical evaluations by a board-certified neuroradiologist confirmed that MedEdit generated realistic stroke scans indistinguishable from real ones. We believe this work will enable counterfactual image editing research to further advance the development of realistic and clinically useful imaging tools.

Diffusion Models for Unsupervised Anomaly Detection in Fetal Brain Ultrasound

Ultrasonography is an essential tool in mid-pregnancy for assessing fetal development, appreciated for its non-invasive and real-time imaging capabilities. Yet, the interpretation of ultrasound images is often complicated by acoustic shadows, speckle noise, and other artifacts that obscure crucial diagnostic details. To address these challenges, our study presents a novel unsupervised anomaly detection framework specifically designed for fetal ultrasound imaging. This framework incorporates gestational age filtering, precise identification of fetal standard planes, and targeted segmentation of brain regions to enhance diagnostic accuracy. Furthermore, we introduce the use of denoising diffusion probabilistic models in this context, marking a significant innovation in detecting previously unrecognized anomalies. We rigorously evaluated the framework using various diffusion-based anomaly detection methods, noise types, and noise levels. Notably, AutoDDPM emerged as the most effective, achieving an area under the precision-recall curve of 79.8\% in detecting anomalies. This advancement holds promise for improving the tools available for nuanced and effective prenatal diagnostics.

Unsupervised Analysis of Alzheimer's Disease Signatures using 3D Deformable Autoencoders

With the increasing incidence of neurodegenerative diseases such as Alzheimer's Disease (AD), there is a need for further research that enhances detection and monitoring of the diseases. We present MORPHADE (Morphological Autoencoders for Alzheimer's Disease Detection), a novel unsupervised learning approach which uses deformations to allow the analysis of 3D T1-weighted brain images. To the best of our knowledge, this is the first use of deformations with deep unsupervised learning to not only detect, but also localize and assess the severity of structural changes in the brain due to AD. We obtain markedly higher anomaly scores in clinically important areas of the brain in subjects with AD compared to healthy controls, showcasing that our method is able to effectively locate AD-related atrophy. We additionally observe a visual correlation between the severity of atrophy highlighted in our anomaly maps and medial temporal lobe atrophy scores evaluated by a clinical expert. Finally, our method achieves an AUROC of 0.80 in detecting AD, out-performing several supervised and unsupervised baselines. We believe our framework shows promise as a tool towards improved understanding, monitoring and detection of AD. To support further research and application, we have made our code publicly available at github.com/ci-ber/MORPHADE.

Interpretable Representation Learning of Cardiac MRI via Attribute Regularization

Interpretability is essential in medical imaging to ensure that clinicians can comprehend and trust artificial intelligence models. Several approaches have been recently considered to encode attributes in the latent space to enhance its interpretability. Notably, attribute regularization aims to encode a set of attributes along the dimensions of a latent representation. However, this approach is based on Variational AutoEncoder and suffers from blurry reconstruction. In this paper, we propose an Attributed-regularized Soft Introspective Variational Autoencoder that combines attribute regularization of the latent space within the framework of an adversarially trained variational autoencoder. We demonstrate on short-axis cardiac Magnetic Resonance images of the UK Biobank the ability of the proposed method to address blurry reconstruction issues of variational autoencoder methods while preserving the latent space interpretability.

Multi-Image Visual Question Answering for Unsupervised Anomaly Detection

Unsupervised anomaly detection enables the identification of potential pathological areas by juxtaposing original images with their pseudo-healthy reconstructions generated by models trained exclusively on normal images. However, the clinical interpretation of resultant anomaly maps presents a challenge due to a lack of detailed, understandable explanations. Recent advancements in language models have shown the capability of mimicking human-like understanding and providing detailed descriptions. This raises an interesting question: \textit{How can language models be employed to make the anomaly maps more explainable?} To the best of our knowledge, we are the first to leverage a language model for unsupervised anomaly detection, for which we construct a dataset with different questions and answers. Additionally, we present a novel multi-image visual question answering framework tailored for anomaly detection, incorporating diverse feature fusion strategies to enhance visual knowledge extraction. Our experiments reveal that the framework, augmented by our new Knowledge Q-Former module, adeptly answers questions on the anomaly detection dataset. Besides, integrating anomaly maps as inputs distinctly aids in improving the detection of unseen pathologies.

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.

Diffusion Models with Implicit Guidance for Medical Anomaly Detection

Diffusion models have advanced unsupervised anomaly detection by improving the transformation of pathological images into pseudo-healthy equivalents. Nonetheless, standard approaches may compromise critical information during pathology removal, leading to restorations that do not align with unaffected regions in the original scans. Such discrepancies can inadvertently increase false positive rates and reduce specificity, complicating radiological evaluations. This paper introduces Temporal Harmonization for Optimal Restoration (THOR), which refines the de-noising process by integrating implicit guidance through temporal anomaly maps. THOR aims to preserve the integrity of healthy tissue in areas unaffected by pathology. Comparative evaluations show that THOR surpasses existing diffusion-based methods in detecting and segmenting anomalies in brain MRIs and wrist X-rays. Code: https://github.com/ci-ber/THOR_DDPM.

Towards Universal Unsupervised Anomaly Detection in Medical Imaging

The increasing complexity of medical imaging data underscores the need for advanced anomaly detection methods to automatically identify diverse pathologies. Current methods face challenges in capturing the broad spectrum of anomalies, often limiting their use to specific lesion types in brain scans. To address this challenge, we introduce a novel unsupervised approach, termed \textit{Reversed Auto-Encoders (RA)}, designed to create realistic pseudo-healthy reconstructions that enable the detection of a wider range of pathologies. We evaluate the proposed method across various imaging modalities, including magnetic resonance imaging (MRI) of the brain, pediatric wrist X-ray, and chest X-ray, and demonstrate superior performance in detecting anomalies compared to existing state-of-the-art methods. Our unsupervised anomaly detection approach may enhance diagnostic accuracy in medical imaging by identifying a broader range of unknown pathologies. Our code is publicly available at: \url{https://github.com/ci-ber/RA}.