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Histopathology, the microscopic study of diseased tissue, is increasingly digitized, enabling improved visualization and streamlined workflows. An important task in histopathology is the segmentation of cells and glands, essential for determining shape and frequencies that can serve as indicators of disease. Deep learning tools are widely used in histopathology. However, variability in tissue appearance and cell morphology presents challenges for achieving reliable segmentation, often requiring manual correction to improve accuracy. This work introduces CellPilot, a framework that bridges the gap between automatic and interactive segmentation by providing initial automatic segmentation as well as guided interactive refinement. Our model was trained on over 675,000 masks of nine diverse cell and gland segmentation datasets, spanning 16 organs. CellPilot demonstrates superior performance compared to other interactive tools on three held-out histopathological datasets while enabling automatic segmentation. We make the model and a graphical user interface designed to assist practitioners in creating large-scale annotated datasets available as open-source, fostering the development of more robust and generalized diagnostic models.

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.

Deep learning models in medical imaging often encounter challenges when adapting to new clinical settings unseen during training. Test-time adaptation offers a promising approach to optimize models for these unseen domains, yet its application in anomaly detection (AD) remains largely unexplored. AD aims to efficiently identify deviations from normative distributions; however, full adaptation, including pathological shifts, may inadvertently learn the anomalies it intends to detect. We introduce a novel concept of selective test-time adaptation that utilizes the inherent characteristics of deep pre-trained features to adapt selectively in a zero-shot manner to any test image from an unseen domain. This approach employs a model-agnostic, lightweight multi-layer perceptron for neural implicit representations, enabling the adaptation of outputs from any reconstruction-based AD method without altering the source-trained model. Rigorous validation in brain AD demonstrated that our strategy substantially enhances detection accuracy for multiple conditions and different target distributions. Specifically, our method improves the detection rates by up to 78% for enlarged ventricles and 24% for edemas., Comment: MICCAIw ADSMI 2024 [Best Paper Award]

This paper presents a method for virtual contrast enhancement in breast MRI, offering a promising non-invasive alternative to traditional contrast agent-based DCE-MRI acquisition. Using a conditional generative adversarial network, we predict DCE-MRI images, including jointly-generated sequences of multiple corresponding DCE-MRI timepoints, from non-contrast-enhanced MRIs, enabling tumor localization and characterization without the associated health risks. Furthermore, we qualitatively and quantitatively evaluate the synthetic DCE-MRI images, proposing a multi-metric Scaled Aggregate Measure (SAMe), assessing their utility in a tumor segmentation downstream task, and conclude with an analysis of the temporal patterns in multi-sequence DCE-MRI generation. Our approach demonstrates promising results in generating realistic and useful DCE-MRI sequences, highlighting the potential of virtual contrast enhancement for improving breast cancer diagnosis and treatment, particularly for patients where contrast agent administration is contraindicated.

Background: The integration of multi-stain histopathology images through deep learning poses a significant challenge in digital histopathology. Current multi-modal approaches struggle with data heterogeneity and missing data. This study aims to overcome these limitations by developing a novel transformer model for multi-stain integration that can handle missing data during training as well as inference. Methods: We propose UNICORN (UNiversal modality Integration Network for CORonary classificatioN) a multi-modal transformer capable of processing multi-stain histopathology for atherosclerosis severity class prediction. The architecture comprises a two-stage, end-to-end trainable model with specialized modules utilizing transformer self-attention blocks. The initial stage employs domain-specific expert modules to extract features from each modality. In the subsequent stage, an aggregation expert module integrates these features by learning the interactions between the different data modalities. Results: Evaluation was performed using a multi-class dataset of atherosclerotic lesions from the Munich Cardiovascular Studies Biobank (MISSION), using over 4,000 paired multi-stain whole slide images (WSIs) from 170 deceased individuals on 7 prespecified segments of the coronary tree, each stained according to four histopathological protocols. UNICORN achieved a classification accuracy of 0.67, outperforming other state-of-the-art models. The model effectively identifies relevant tissue phenotypes across stainings and implicitly models disease progression. Conclusion: Our proposed multi-modal transformer model addresses key challenges in medical data analysis, including data heterogeneity and missing modalities. Explainability and the model's effectiveness in predicting atherosclerosis progression underscores its potential for broader applications in medical research.

We propose in this paper a texture-invariant 2D keypoints descriptor specifically designed for matching preoperative Magnetic Resonance (MR) images with intraoperative Ultrasound (US) images. We introduce a matching-by-synthesis strategy, where intraoperative US images are synthesized from MR images accounting for multiple MR modalities and intraoperative US variability. We build our training set by enforcing keypoints localization over all images then train a patient-specific descriptor network that learns texture-invariant discriminant features in a supervised contrastive manner, leading to robust keypoints descriptors. Our experiments on real cases with ground truth show the effectiveness of the proposed approach, outperforming the state-of-the-art methods and achieving 80.35% matching precision on average., Comment: Accepted for publication at the International Workshop of Advances in Simplifying Medical UltraSound (ASMUS) at MICCAI 2024

Accurate assessment of lymph node size in 3D CT scans is crucial for cancer staging, therapeutic management, and monitoring treatment response. Existing state-of-the-art segmentation frameworks in medical imaging often rely on fully annotated datasets. However, for lymph node segmentation, these datasets are typically small due to the extensive time and expertise required to annotate the numerous lymph nodes in 3D CT scans. Weakly-supervised learning, which leverages incomplete or noisy annotations, has recently gained interest in the medical imaging community as a potential solution. Despite the variety of weakly-supervised techniques proposed, most have been validated only on private datasets or small publicly available datasets. To address this limitation, the Mediastinal Lymph Node Quantification (LNQ) challenge was organized in conjunction with the 26th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2023). This challenge aimed to advance weakly-supervised segmentation methods by providing a new, partially annotated dataset and a robust evaluation framework. A total of 16 teams from 5 countries submitted predictions to the validation leaderboard, and 6 teams from 3 countries participated in the evaluation phase. The results highlighted both the potential and the current limitations of weakly-supervised approaches. On one hand, weakly-supervised approaches obtained relatively good performance with a median Dice score of $61.0\%$. On the other hand, top-ranked teams, with a median Dice score exceeding $70\%$, boosted their performance by leveraging smaller but fully annotated datasets to combine weak supervision and full supervision. This highlights both the promise of weakly-supervised methods and the ongoing need for high-quality, fully annotated data to achieve higher segmentation performance., Comment: Submitted to MELBA

Recent studies have underscored the capabilities of natural imaging foundation models to serve as powerful feature extractors, even in a zero-shot setting for medical imaging data. Most commonly, a shallow multi-layer perceptron (MLP) is appended to the feature extractor to facilitate end-to-end learning and downstream prediction tasks such as classification, thus representing the de facto standard. However, as graph neural networks (GNNs) have become a practicable choice for various tasks in medical research in the recent past, we direct attention to the question of how effective GNNs are compared to MLP prediction heads for the task of 3D medical image classification, proposing them as a potential alternative. In our experiments, we devise a subject-level graph for each volumetric dataset instance. Therein latent representations of all slices in the volume, encoded through a DINOv2 pretrained vision transformer (ViT), constitute the nodes and their respective node features. We use public datasets to compare the classification heads numerically and evaluate various graph construction and graph convolution methods in our experiments. Our findings show enhancements of the GNN in classification performance and substantial improvements in runtime compared to an MLP prediction head. Additional robustness evaluations further validate the promising performance of the GNN, promoting them as a suitable alternative to traditional MLP classification heads. Our code is publicly available at: https://github.com/compai-lab/2024-miccai-grail-kiechle, Comment: Accepted at MICCAI 2024 - GRAIL Workshop

High-grade serous ovarian carcinoma (HGSOC) is characterised by significant spatial and temporal heterogeneity, typically manifesting at an advanced metastatic stage. A major challenge in treating advanced HGSOC is effectively monitoring localised change in tumour burden across multiple sites during neoadjuvant chemotherapy (NACT) and predicting long-term pathological response and overall patient survival. In this work, we propose a self-supervised deformable image registration algorithm that utilises a general-purpose image encoder for image feature extraction to co-register contrast-enhanced computerised tomography scan images acquired before and after neoadjuvant chemotherapy. This approach addresses challenges posed by highly complex tumour deformations and longitudinal lesion matching during treatment. Localised tumour changes are calculated using the Jacobian determinant maps of the registration deformation at multiple disease sites and their macroscopic areas, including hypo-dense (i.e., cystic/necrotic), hyper-dense (i.e., calcified), and intermediate density (i.e., soft tissue) portions. A series of experiments is conducted to understand the role of a general-purpose image encoder and its application in quantifying change in tumour burden during neoadjuvant chemotherapy in HGSOC. This work is the first to demonstrate the feasibility of a self-supervised image registration approach in quantifying NACT-induced localised tumour changes across the whole disease burden of patients with complex multi-site HGSOC, which could be used as a potential marker for ovarian cancer patient's long-term pathological response and survival.

Generally, the small size of public medical imaging datasets coupled with stringent privacy concerns, hampers the advancement of data-hungry deep learning models in medical imaging. This study addresses these challenges for 3D cardiac MRI images in the short-axis view. We propose Latent Diffusion Models that generate synthetic images conditioned on medical attributes, while ensuring patient privacy through differentially private model training. To our knowledge, this is the first work to apply and quantify differential privacy in 3D medical image generation. We pre-train our models on public data and finetune them with differential privacy on the UK Biobank dataset. Our experiments reveal that pre-training significantly improves model performance, achieving a Fr\'echet Inception Distance (FID) of 26.77 at $\epsilon=10$, compared to 92.52 for models without pre-training. Additionally, we explore the trade-off between privacy constraints and image quality, investigating how tighter privacy budgets affect output controllability and may lead to degraded performance. Our results demonstrate that proper consideration during training with differential privacy can substantially improve the quality of synthetic cardiac MRI images, but there are still notable challenges in achieving consistent medical realism.

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., Comment: Accepted at MICCAI24 Simulation and Synthesis in Medical Imaging (SASHIMI) workshop

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., Comment: ASMUS 2024: 5th International Workshop on Advances in Simplifying Medical Ultrasound

General vision encoders like DINOv2 and SAM have recently transformed computer vision. Even though they are trained on natural images, such encoder models have excelled in medical imaging, e.g., in classification, segmentation, and registration. However, no in-depth comparison of different state-of-the-art general vision encoders for medical registration is available. In this work, we investigate how well general vision encoder features can be used in the dissimilarity metrics for medical image registration. We explore two encoders that were trained on natural images as well as one that was fine-tuned on medical data. We apply the features within the well-established B-spline FFD registration framework. In extensive experiments on cardiac cine MRI data, we find that using features as additional guidance for conventional metrics improves the registration quality. The code is available at github.com/compai-lab/2024-miccai-koegl., Comment: Accepted at WBIR MICCAI 2024

Current deep learning-based low-light image enhancement methods often struggle with high-resolution images, and fail to meet the practical demands of visual perception across diverse and unseen scenarios. In this paper, we introduce a novel approach termed CoLIE, which redefines the enhancement process through mapping the 2D coordinates of an underexposed image to its illumination component, conditioned on local context. We propose a reconstruction of enhanced-light images within the HSV space utilizing an implicit neural function combined with an embedded guided filter, thereby significantly reducing computational overhead. Moreover, we introduce a single image-based training loss function to enhance the model's adaptability to various scenes, further enhancing its practical applicability. Through rigorous evaluations, we analyze the properties of our proposed framework, demonstrating its superiority in both image quality and scene adaptability. Furthermore, our evaluation extends to applications in downstream tasks within low-light scenarios, underscoring the practical utility of CoLIE. The source code is available at https://github.com/ctom2/colie., Comment: Accepted to ECCV24

Deep learning holds immense promise for aiding radiologists in breast cancer detection. However, achieving optimal model performance is hampered by limitations in availability and sharing of data commonly associated to patient privacy concerns. Such concerns are further exacerbated, as traditional deep learning models can inadvertently leak sensitive training information. This work addresses these challenges exploring and quantifying the utility of privacy-preserving deep learning techniques, concretely, (i) differentially private stochastic gradient descent (DP-SGD) and (ii) fully synthetic training data generated by our proposed malignancy-conditioned generative adversarial network. We assess these methods via downstream malignancy classification of mammography masses using a transformer model. Our experimental results depict that synthetic data augmentation can improve privacy-utility tradeoffs in differentially private model training. Further, model pretraining on synthetic data achieves remarkable performance, which can be further increased with DP-SGD fine-tuning across all privacy guarantees. With this first in-depth exploration of privacy-preserving deep learning in breast imaging, we address current and emerging clinical privacy requirements and pave the way towards the adoption of private high-utility deep diagnostic models. Our reproducible codebase is publicly available at https://github.com/RichardObi/mammo_dp., Comment: Early Accept at MICCAI 2024 Deep-Breath Workshop

In this work, we introduce Progressive Growing of Patch Size, a resource-efficient implicit curriculum learning approach for dense prediction tasks. Our curriculum approach is defined by growing the patch size during model training, which gradually increases the task's difficulty. We integrated our curriculum into the nnU-Net framework and evaluated the methodology on all 10 tasks of the Medical Segmentation Decathlon. With our approach, we are able to substantially reduce runtime, computational costs, and CO2 emissions of network training compared to classical constant patch size training. In our experiments, the curriculum approach resulted in improved convergence. We are able to outperform standard nnU-Net training, which is trained with constant patch size, in terms of Dice Score on 7 out of 10 MSD tasks while only spending roughly 50% of the original training runtime. To the best of our knowledge, our Progressive Growing of Patch Size is the first successful employment of a sample-length curriculum in the form of patch size in the field of computer vision. Our code is publicly available at https://github.com/compai-lab/2024-miccai-fischer., Comment: Accepted at MICCAI2024; Changes for Camera-Ready-Version for MICCAI2024 (missing in this arxiv submission): Replaced T-Test with Wilcoxon Signed Ranked Test, as DSC samples are not normally distributed => now only significant improvements and no significant decreases in performance for PGPS/PGPS+

Machine unlearning is the process of removing the impact of a particular set of training samples from a pretrained model. It aims to fulfill the "right to be forgotten", which grants the individuals such as patients the right to reconsider their contribution in models including medical imaging models. In this study, we evaluate the effectiveness (performance) and computational efficiency of different unlearning algorithms in medical imaging domain. Our evaluations demonstrate that the considered unlearning algorithms perform well on the retain set (samples whose influence on the model is allowed to be retained) and forget set (samples whose contribution to the model should be eliminated), and show no bias against male or female samples. They, however, adversely impact the generalization of the model, especially for larger forget set sizes. Moreover, they might be biased against easy or hard samples, and need additional computational overhead for hyper-parameter tuning. In conclusion, machine unlearning seems promising for medical imaging, but the existing unlearning algorithms still needs further improvements to become more practical for medical applications.

Physics-inspired regularization is desired for intra-patient image registration since it can effectively capture the biomechanical characteristics of anatomical structures. However, a major challenge lies in the reliance on physical parameters: Parameter estimations vary widely across the literature, and the physical properties themselves are inherently subject-specific. In this work, we introduce a novel data-driven method that leverages hypernetworks to learn the tissue-dependent elasticity parameters of an elastic regularizer. Notably, our approach facilitates the estimation of patient-specific parameters without the need to retrain the network. We evaluate our method on three publicly available 2D and 3D lung CT and cardiac MR datasets. We find that with our proposed subject-specific tissue-dependent regularization, a higher registration quality is achieved across all datasets compared to using a global regularizer. The code is available at https://github.com/compai-lab/2024-miccai-reithmeir., Comment: Accepted at MICCAI 2024

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., Comment: 11 pages, 5 figures

Deep learning models for medical image segmentation and object detection are becoming increasingly available as clinical products. However, as details are rarely provided about the training data, models may unexpectedly fail when cases differ from those in the training distribution. An approach allowing potential users to independently test the robustness of a model, treating it as a black box and using only a few cases from their own site, is key for adoption. To address this, a method to test the robustness of these models against CT image quality variation is presented. In this work we present this framework by demonstrating that given the same training data, the model architecture and data pre processing greatly affect the robustness of several frequently used segmentation and object detection methods to simulated CT imaging artifacts and degradation. Our framework also addresses the concern about the sustainability of deep learning models in clinical use, by considering future shifts in image quality due to scanner deterioration or imaging protocol changes which are not reflected in a limited local test dataset.

Pathological lymph node delineation is crucial in cancer diagnosis, progression assessment, and treatment planning. The MICCAI 2023 Lymph Node Quantification Challenge published the first public dataset for pathological lymph node segmentation in the mediastinum. As lymph node annotations are expensive, the challenge was formed as a weakly supervised learning task, where only a subset of all lymph nodes in the training set have been annotated. For the challenge submission, multiple methods for training on these weakly supervised data were explored, including noisy label training, loss masking of unlabeled data, and an approach that integrated the TotalSegmentator toolbox as a form of pseudo labeling in order to reduce the number of unknown voxels. Furthermore, multiple public TCIA datasets were incorporated into the training to improve the performance of the deep learning model. Our submitted model achieved a Dice score of 0.628 and an average symmetric surface distance of 5.8~mm on the challenge test set. With our submitted model, we accomplished third rank in the MICCAI2023 LNQ challenge. A finding of our analysis was that the integration of all visible, including non-pathological, lymph nodes improved the overall segmentation performance on pathological lymph nodes of the test set. Furthermore, segmentation models trained only on clinically enlarged lymph nodes, as given in the challenge scenario, could not generalize to smaller pathological lymph nodes. The code and model for the challenge submission are available at \url{https://gitlab.lrz.de/compai/MediastinalLymphNodeSegmentation}., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2024:008

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., Comment: arXiv admin note: substantial text overlap with arXiv:2312.08915

Purpose: To develop and evaluate a deep learning model for multi-organ segmentation of MRI scans. Materials and Methods: The model was trained on 1,200 manually annotated 3D axial MRI scans from the UK Biobank, 221 in-house MRI scans, and 1228 CT scans from the TotalSegmentator dataset. A human-in-the-loop annotation workflow was employed, leveraging cross-modality transfer learning from an existing CT segmentation model to segment 40 anatomical structures. The annotation process began with a model based on transfer learning between CT and MR, which was iteratively refined based on manual corrections to predicted segmentations. The model's performance was evaluated on MRI examinations obtained from the German National Cohort (NAKO) study (n=900) from the AMOS22 dataset (n=60) and from the TotalSegmentator-MRI test data (n=29). The Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD) were used to assess segmentation quality, stratified by organ and scan type. The model and its weights will be open-sourced. Results: MRSegmentator demonstrated high accuracy for well-defined organs (lungs: DSC 0.96, heart: DSC 0.94) and organs with anatomic variability (liver: DSC 0.96, kidneys: DSC 0.95). Smaller structures showed lower accuracy (portal/splenic veins: DSC 0.64, adrenal glands: DSC 0.69). On external validation using NAKO data, mean DSC ranged from 0.85 $\pm$ 0.08 for T2-HASTE to 0.91 $\pm$ 0.05 for in-phase sequences. The model generalized well to CT, achieving mean DSC of 0.84 $\pm$ 0.11 on AMOS CT data. Conclusion: MRSegmentator accurately segments 40 anatomical structures in MRI across diverse datasets and imaging protocols, with additional generalizability to CT images. This open-source model will provide a valuable tool for automated multi-organ segmentation in medical imaging research. It can be downloaded from https://github.com/hhaentze/MRSegmentator., Comment: 17 pages, 6 figures; updated data; completed co-author info

Neural implicit k-space representations have shown promising results for dynamic MRI at high temporal resolutions. Yet, their exclusive training in k-space limits the application of common image regularization methods to improve the final reconstruction. In this work, we introduce the concept of parallel imaging-inspired self-consistency (PISCO), which we incorporate as novel self-supervised k-space regularization enforcing a consistent neighborhood relationship. At no additional data cost, the proposed regularization significantly improves neural implicit k-space reconstructions on simulated data. Abdominal in-vivo reconstructions using PISCO result in enhanced spatio-temporal image quality compared to state-of-the-art methods. Code is available at https://github.com/vjspi/PISCO-NIK., Comment: Under Review

This research explores the integration of language models and unsupervised anomaly detection in medical imaging, addressing two key questions: (1) Can language models enhance the interpretability of anomaly detection maps? and (2) Can anomaly maps improve the generalizability of language models in open-set anomaly detection tasks? To investigate these questions, we introduce a new dataset for multi-image visual question-answering on brain magnetic resonance images encompassing multiple conditions. We propose KQ-Former (Knowledge Querying Transformer), which is designed to optimally align visual and textual information in limited-sample contexts. Our model achieves a 60.81% accuracy on closed questions, covering disease classification and severity across 15 different classes. For open questions, KQ-Former demonstrates a 70% improvement over the baseline with a BLEU-4 score of 0.41, and achieves the highest entailment ratios (up to 71.9%) and lowest contradiction ratios (down to 10.0%) among various natural language inference models. Furthermore, integrating anomaly maps results in an 18% accuracy increase in detecting open-set anomalies, thereby enhancing the language model's generalizability to previously unseen medical conditions. The code and dataset are available at https://github.com/compai-lab/miccai-2024-junli?tab=readme-ov-file, Comment: 13 pages, 7 figures. 5th International Workshop on Multiscale Multimodal Medical Imaging (MMMI 2024)

In hematology, computational models offer significant potential to improve diagnostic accuracy, streamline workflows, and reduce the tedious work of analyzing single cells in peripheral blood or bone marrow smears. However, clinical adoption of computational models has been hampered by the lack of generalization due to large batch effects, small dataset sizes, and poor performance in transfer learning from natural images. To address these challenges, we introduce DinoBloom, the first foundation model for single cell images in hematology, utilizing a tailored DINOv2 pipeline. Our model is built upon an extensive collection of 13 diverse, publicly available datasets of peripheral blood and bone marrow smears, the most substantial open-source cohort in hematology so far, comprising over 380,000 white blood cell images. To assess its generalization capability, we evaluate it on an external dataset with a challenging domain shift. We show that our model outperforms existing medical and non-medical vision models in (i) linear probing and k-nearest neighbor evaluations for cell-type classification on blood and bone marrow smears and (ii) weakly supervised multiple instance learning for acute myeloid leukemia subtyping by a large margin. A family of four DinoBloom models (small, base, large, and giant) can be adapted for a wide range of downstream applications, be a strong baseline for classification problems, and facilitate the assessment of batch effects in new datasets. All models are available at github.com/marrlab/DinoBloom.

Contrast agents in dynamic contrast enhanced magnetic resonance imaging allow to localize tumors and observe their contrast kinetics, which is essential for cancer characterization and respective treatment decision-making. However, contrast agent administration is not only associated with adverse health risks, but also restricted for patients during pregnancy, and for those with kidney malfunction, or other adverse reactions. With contrast uptake as key biomarker for lesion malignancy, cancer recurrence risk, and treatment response, it becomes pivotal to reduce the dependency on intravenous contrast agent administration. To this end, we propose a multi-conditional latent diffusion model capable of acquisition time-conditioned image synthesis of DCE-MRI temporal sequences. To evaluate medical image synthesis, we additionally propose and validate the Fr\'echet radiomics distance as an image quality measure based on biomarker variability between synthetic and real imaging data. Our results demonstrate our method's ability to generate realistic multi-sequence fat-saturated breast DCE-MRI and uncover the emerging potential of deep learning based contrast kinetics simulation. We publicly share our accessible codebase at https://github.com/RichardObi/ccnet and provide a user-friendly library for Fr\'echet radiomics distance calculation at https://pypi.org/project/frd-score., Comment: Early Accept at MICCAI2024

We propose PHIMO, a physics-informed learning-based motion correction method tailored to quantitative MRI. PHIMO leverages information from the signal evolution to exclude motion-corrupted k-space lines from a data-consistent reconstruction. We demonstrate the potential of PHIMO for the application of T2* quantification from gradient echo MRI, which is particularly sensitive to motion due to its sensitivity to magnetic field inhomogeneities. A state-of-the-art technique for motion correction requires redundant acquisition of the k-space center, prolonging the acquisition. We show that PHIMO can detect and exclude intra-scan motion events and, thus, correct for severe motion artifacts. PHIMO approaches the performance of the state-of-the-art motion correction method, while substantially reducing the acquisition time by over 40%, facilitating clinical applicability. Our code is available at https://github.com/HannahEichhorn/PHIMO., Comment: Accepted at MICCAI 2024

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.

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}.

To handle the large scale of whole slide images in computational pathology, most approaches first tessellate the images into smaller patches, extract features from these patches, and finally aggregate the feature vectors with weakly-supervised learning. The performance of this workflow strongly depends on the quality of the extracted features. Recently, foundation models in computer vision showed that leveraging huge amounts of data through supervised or self-supervised learning improves feature quality and generalizability for a variety of tasks. In this study, we benchmark the most popular vision foundation models as feature extractors for histopathology data. We evaluate the models in two settings: slide-level classification and patch-level classification. We show that foundation models are a strong baseline. Our experiments demonstrate that by finetuning a foundation model on a single GPU for only two hours or three days depending on the dataset, we can match or outperform state-of-the-art feature extractors for computational pathology. These findings imply that even with little resources one can finetune a feature extractor tailored towards a specific downstream task and dataset. This is a considerable shift from the current state, where only few institutions with large amounts of resources and datasets are able to train a feature extractor. We publish all code used for training and evaluation as well as the finetuned models.

Interpretability is essential in medical imaging to ensure that clinicians can comprehend and trust artificial intelligence models. In this paper, we propose a novel interpretable approach that combines attribute regularization of the latent space within the framework of an adversarially trained variational autoencoder. Comparative experiments on a cardiac MRI dataset demonstrate the ability of the proposed method to address blurry reconstruction issues of variational autoencoder methods and improve latent space interpretability. Additionally, our analysis of a downstream task reveals that the classification of cardiac disease using the regularized latent space heavily relies on attribute regularized dimensions, demonstrating great interpretability by connecting the used attributes for prediction with clinical observations.

The Segment Anything Model (SAM) has recently emerged as a significant breakthrough in foundation models, demonstrating remarkable zero-shot performance in object segmentation tasks. While SAM is designed for generalization, it exhibits limitations in handling specific medical imaging tasks that require fine-structure segmentation or precise boundaries. In this paper, we focus on the task of cardiac magnetic resonance imaging (cMRI) short-axis view segmentation using the SAM foundation model. We conduct a comprehensive investigation of the impact of different prompting strategies (including bounding boxes, positive points, negative points, and their combinations) on segmentation performance. We evaluate on two public datasets using the baseline model and models fine-tuned with varying amounts of annotated data, ranging from a limited number of volumes to a fully annotated dataset. Our findings indicate that prompting strategies significantly influence segmentation performance. Combining positive points with either bounding boxes or negative points shows substantial benefits, but little to no benefit when combined simultaneously. We further observe that fine-tuning SAM with a few annotated volumes improves segmentation performance when properly prompted. Specifically, fine-tuning with bounding boxes has a positive impact, while fine-tuning without bounding boxes leads to worse results compared to baseline.

Medical image registration aims at identifying the spatial deformation between images of the same anatomical region and is fundamental to image-based diagnostics and therapy. To date, the majority of the deep learning-based registration methods employ regularizers that enforce global spatial smoothness, e.g., the diffusion regularizer. However, such regularizers are not tailored to the data and might not be capable of reflecting the complex underlying deformation. In contrast, physics-inspired regularizers promote physically plausible deformations. One such regularizer is the linear elastic regularizer which models the deformation of elastic material. These regularizers are driven by parameters that define the material's physical properties. For biological tissue, a wide range of estimations of such parameters can be found in the literature and it remains an open challenge to identify suitable parameter values for successful registration. To overcome this problem and to incorporate physical properties into learning-based registration, we propose to use a hypernetwork that learns the effect of the physical parameters of a physics-inspired regularizer on the resulting spatial deformation field. In particular, we adapt the HyperMorph framework to learn the effect of the two elasticity parameters of the linear elastic regularizer. Our approach enables the efficient discovery of suitable, data-specific physical parameters at test time., Comment: Manuscript accepted at SPIE Medical Imaging 2024

The skeleton of a digital image is a compact representation of its topology, geometry, and scale. It has utility in many computer vision applications, such as image description, segmentation, and registration. However, skeletonization has only seen limited use in contemporary deep learning solutions. Most existing skeletonization algorithms are not differentiable, making it impossible to integrate them with gradient-based optimization. Compatible algorithms based on morphological operations and neural networks have been proposed, but their results often deviate from the geometry and topology of the true medial axis. This work introduces the first three-dimensional skeletonization algorithm that is both compatible with gradient-based optimization and preserves an object's topology. Our method is exclusively based on matrix additions and multiplications, convolutional operations, basic non-linear functions, and sampling from a uniform probability distribution, allowing it to be easily implemented in any major deep learning library. In benchmarking experiments, we prove the advantages of our skeletonization algorithm compared to non-differentiable, morphological, and neural-network-based baselines. Finally, we demonstrate the utility of our algorithm by integrating it with two medical image processing applications that use gradient-based optimization: deep-learning-based blood vessel segmentation, and multimodal registration of the mandible in computed tomography and magnetic resonance images., Comment: Accepted at ICCV 2023

Unsupervised anomaly detection methods offer a promising and flexible alternative to supervised approaches, holding the potential to revolutionize medical scan analysis and enhance diagnostic performance. In the current landscape, it is commonly assumed that differences between a test case and the training distribution are attributed solely to pathological conditions, implying that any disparity indicates an anomaly. However, the presence of other potential sources of distributional shift, including scanner, age, sex, or race, is frequently overlooked. These shifts can significantly impact the accuracy of the anomaly detection task. Prominent instances of such failures have sparked concerns regarding the bias, credibility, and fairness of anomaly detection. This work presents a novel analysis of biases in unsupervised anomaly detection. By examining potential non-pathological distributional shifts between the training and testing distributions, we shed light on the extent of these biases and their influence on anomaly detection results. Moreover, this study examines the algorithmic limitations that arise due to biases, providing valuable insights into the challenges encountered by anomaly detection algorithms in accurately learning and capturing the entire range of variability present in the normative distribution. Through this analysis, we aim to enhance the understanding of these biases and pave the way for future improvements in the field. Here, we specifically investigate Alzheimer's disease detection from brain MR imaging as a case study, revealing significant biases related to sex, race, and scanner variations that substantially impact the results. These findings align with the broader goal of improving the reliability, fairness, and effectiveness of anomaly detection in medical imaging.

Motion-resolved reconstruction for abdominal magnetic resonance imaging (MRI) remains a challenge due to the trade-off between residual motion blurring caused by discretized motion states and undersampling artefacts. In this work, we propose to generate blurring-free motion-resolved abdominal reconstructions by learning a neural implicit representation directly in k-space (NIK). Using measured sampling points and a data-derived respiratory navigator signal, we train a network to generate continuous signal values. To aid the regularization of sparsely sampled regions, we introduce an additional informed correction layer (ICo), which leverages information from neighboring regions to correct NIK's prediction. Our proposed generative reconstruction methods, NIK and ICoNIK, outperform standard motion-resolved reconstruction techniques and provide a promising solution to address motion artefacts in abdominal MRI.

Despite major advances in artificial intelligence (AI) for medicine and healthcare, the deployment and adoption of AI technologies remain limited in real-world clinical practice. In recent years, concerns have been raised about the technical, clinical, ethical and legal risks associated with medical AI. To increase real world adoption, it is essential that medical AI tools are trusted and accepted by patients, clinicians, health organisations and authorities. This work describes the FUTURE-AI guideline as the first international consensus framework for guiding the development and deployment of trustworthy AI tools in healthcare. The FUTURE-AI consortium was founded in 2021 and currently comprises 118 inter-disciplinary experts from 51 countries representing all continents, including AI scientists, clinicians, ethicists, and social scientists. Over a two-year period, the consortium defined guiding principles and best practices for trustworthy AI through an iterative process comprising an in-depth literature review, a modified Delphi survey, and online consensus meetings. The FUTURE-AI framework was established based on 6 guiding principles for trustworthy AI in healthcare, i.e. Fairness, Universality, Traceability, Usability, Robustness and Explainability. Through consensus, a set of 28 best practices were defined, addressing technical, clinical, legal and socio-ethical dimensions. The recommendations cover the entire lifecycle of medical AI, from design, development and validation to regulation, deployment, and monitoring. FUTURE-AI is a risk-informed, assumption-free guideline which provides a structured approach for constructing medical AI tools that will be trusted, deployed and adopted in real-world practice. Researchers are encouraged to take the recommendations into account in proof-of-concept stages to facilitate future translation towards clinical practice of medical AI.

Short axis cardiac MRI segmentation is a well-researched topic, with excellent results achieved by state-of-the-art models in a supervised setting. However, annotating MRI volumes is time-consuming and expensive. Many different approaches (e.g. transfer learning, data augmentation, few-shot learning, etc.) have emerged in an effort to use fewer annotated data and still achieve similar performance as a fully supervised model. Nevertheless, to the best of our knowledge, none of these works focus on which slices of MRI volumes are most important to annotate for yielding the best segmentation results. In this paper, we investigate the effects of training with sparse volumes, i.e. reducing the number of cases annotated, and sparse annotations, i.e. reducing the number of slices annotated per case. We evaluate the segmentation performance using the state-of-the-art nnU-Net model on two public datasets to identify which slices are the most important to annotate. We have shown that training on a significantly reduced dataset (48 annotated volumes) can give a Dice score greater than 0.85 and results comparable to using the full dataset (160 and 240 volumes for each dataset respectively). In general, training on more slice annotations provides more valuable information compared to training on more volumes. Further, annotating slices from the middle of volumes yields the most beneficial results in terms of segmentation performance, and the apical region the worst. When evaluating the trade-off between annotating volumes against slices, annotating as many slices as possible instead of annotating more volumes is a better strategy.

Deep generative models have emerged as influential instruments for data generation and manipulation. Enhancing the controllability of these models by selectively modifying data attributes has been a recent focus. Variational Autoencoders (VAEs) have shown promise in capturing hidden attributes but often produce blurry reconstructions. Controlling these attributes through different imaging domains is difficult in medical imaging. Recently, Soft Introspective VAE leverage the benefits of both VAEs and Generative Adversarial Networks (GANs), which have demonstrated impressive image synthesis capabilities, by incorporating an adversarial loss into VAE training. In this work, we propose the Attributed Soft Introspective VAE (Attri-SIVAE) by incorporating an attribute regularized loss, into the Soft-Intro VAE framework. We evaluate experimentally the proposed method on cardiac MRI data from different domains, such as various scanner vendors and acquisition centers. The proposed method achieves similar performance in terms of reconstruction and regularization compared to the state-of-the-art Attributed regularized VAE but additionally also succeeds in keeping the same regularization level when tested on a different dataset, unlike the compared method., Comment: Not accepted and outdated results

The introduction of diffusion models in anomaly detection has paved the way for more effective and accurate image reconstruction in pathologies. However, the current limitations in controlling noise granularity hinder diffusion models' ability to generalize across diverse anomaly types and compromise the restoration of healthy tissues. To overcome these challenges, we propose AutoDDPM, a novel approach that enhances the robustness of diffusion models. AutoDDPM utilizes diffusion models to generate initial likelihood maps of potential anomalies and seamlessly integrates them with the original image. Through joint noised distribution re-sampling, AutoDDPM achieves harmonization and in-painting effects. Our study demonstrates the efficacy of AutoDDPM in replacing anomalous regions while preserving healthy tissues, considerably surpassing diffusion models' limitations. It also contributes valuable insights and analysis on the limitations of current diffusion models, promoting robust and interpretable anomaly detection in medical imaging - an essential aspect of building autonomous clinical decision systems with higher interpretability.

Motion represents one of the major challenges in magnetic resonance imaging (MRI). Since the MR signal is acquired in frequency space, any motion of the imaged object leads to complex artefacts in the reconstructed image in addition to other MR imaging artefacts. Deep learning has been frequently proposed for motion correction at several stages of the reconstruction process. The wide range of MR acquisition sequences, anatomies and pathologies of interest, and motion patterns (rigid vs. deformable and random vs. regular) makes a comprehensive solution unlikely. To facilitate the transfer of ideas between different applications, this review provides a detailed overview of proposed methods for learning-based motion correction in MRI together with their common challenges and potentials. This review identifies differences and synergies in underlying data usage, architectures, training and evaluation strategies. We critically discuss general trends and outline future directions, with the aim to enhance interaction between different application areas and research fields.