Towards Unifying Anatomy Segmentation: Automated Generation of a Full-body CT Dataset via Knowledge Aggregation and Anatomical Guidelines

In this study, we present a method for generating automated anatomy segmentation datasets using a sequential process that involves nnU-Net-based pseudo-labeling and anatomy-guided pseudo-label refinement. By combining various fragmented knowledge bases, we generate a dataset of whole-body CT scans with $142$ voxel-level labels for 533 volumes providing comprehensive anatomical coverage which experts have approved. Our proposed procedure does not rely on manual annotation during the label aggregation stage. We examine its plausibility and usefulness using three complementary checks: Human expert evaluation which approved the dataset, a Deep Learning usefulness benchmark on the BTCV dataset in which we achieve 85% dice score without using its training dataset, and medical validity checks. This evaluation procedure combines scalable automated checks with labor-intensive high-quality expert checks. Besides the dataset, we release our trained unified anatomical segmentation model capable of predicting $142$ anatomical structures on CT data.

FAM: Relative Flatness Aware Minimization

Flatness of the loss curve around a model at hand has been shown to empirically correlate with its generalization ability. Optimizing for flatness has been proposed as early as 1994 by Hochreiter and Schmidthuber, and was followed by more recent successful sharpness-aware optimization techniques. Their widespread adoption in practice, though, is dubious because of the lack of theoretically grounded connection between flatness and generalization, in particular in light of the reparameterization curse - certain reparameterizations of a neural network change most flatness measures but do not change generalization. Recent theoretical work suggests that a particular relative flatness measure can be connected to generalization and solves the reparameterization curse. In this paper, we derive a regularizer based on this relative flatness that is easy to compute, fast, efficient, and works with arbitrary loss functions. It requires computing the Hessian only of a single layer of the network, which makes it applicable to large neural networks, and with it avoids an expensive mapping of the loss surface in the vicinity of the model. In an extensive empirical evaluation we show that this relative flatness aware minimization (FAM) improves generalization in a multitude of applications and models, both in finetuning and standard training. We make the code available at github.

Why does my medical AI look at pictures of birds? Exploring the efficacy of transfer learning across domain boundaries

It is an open secret that ImageNet is treated as the panacea of pretraining. Particularly in medical machine learning, models not trained from scratch are often finetuned based on ImageNet-pretrained models. We posit that pretraining on data from the domain of the downstream task should almost always be preferred instead. We leverage RadNet-12M, a dataset containing more than 12 million computed tomography (CT) image slices, to explore the efficacy of self-supervised pretraining on medical and natural images. Our experiments cover intra- and cross-domain transfer scenarios, varying data scales, finetuning vs. linear evaluation, and feature space analysis. We observe that intra-domain transfer compares favorably to cross-domain transfer, achieving comparable or improved performance (0.44% - 2.07% performance increase using RadNet pretraining, depending on the experiment) and demonstrate the existence of a domain boundary-related generalization gap and domain-specific learned features.

CellViT: Vision Transformers for Precise Cell Segmentation and Classification

Nuclei detection and segmentation in hematoxylin and eosin-stained (H&E) tissue images are important clinical tasks and crucial for a wide range of applications. However, it is a challenging task due to nuclei variances in staining and size, overlapping boundaries, and nuclei clustering. While convolutional neural networks have been extensively used for this task, we explore the potential of Transformer-based networks in this domain. Therefore, we introduce a new method for automated instance segmentation of cell nuclei in digitized tissue samples using a deep learning architecture based on Vision Transformer called CellViT. CellViT is trained and evaluated on the PanNuke dataset, which is one of the most challenging nuclei instance segmentation datasets, consisting of nearly 200,000 annotated Nuclei into 5 clinically important classes in 19 tissue types. We demonstrate the superiority of large-scale in-domain and out-of-domain pre-trained Vision Transformers by leveraging the recently published Segment Anything Model and a ViT-encoder pre-trained on 104 million histological image patches - achieving state-of-the-art nuclei detection and instance segmentation performance on the PanNuke dataset with a mean panoptic quality of 0.51 and an F1-detection score of 0.83. The code is publicly available at https://github.com/TIO-IKIM/CellViT

Accurate Fine-Grained Segmentation of Human Anatomy in Radiographs via Volumetric Pseudo-Labeling

Purpose: Interpreting chest radiographs (CXR) remains challenging due to the ambiguity of overlapping structures such as the lungs, heart, and bones. To address this issue, we propose a novel method for extracting fine-grained anatomical structures in CXR using pseudo-labeling of three-dimensional computed tomography (CT) scans. Methods: We created a large-scale dataset of 10,021 thoracic CTs with 157 labels and applied an ensemble of 3D anatomy segmentation models to extract anatomical pseudo-labels. These labels were projected onto a two-dimensional plane, similar to the CXR, allowing the training of detailed semantic segmentation models for CXR without any manual annotation effort. Results: Our resulting segmentation models demonstrated remarkable performance on CXR, with a high average model-annotator agreement between two radiologists with mIoU scores of 0.93 and 0.85 for frontal and lateral anatomy, while inter-annotator agreement remained at 0.95 and 0.83 mIoU. Our anatomical segmentations allowed for the accurate extraction of relevant explainable medical features such as the cardio-thoracic-ratio. Conclusion: Our method of volumetric pseudo-labeling paired with CT projection offers a promising approach for detailed anatomical segmentation of CXR with a high agreement with human annotators. This technique may have important clinical implications, particularly in the analysis of various thoracic pathologies.

Mirror U-Net: Marrying Multimodal Fission with Multi-task Learning for Semantic Segmentation in Medical Imaging

Positron Emission Tomography (PET) and Computer Tomography (CT) are routinely used together to detect tumors. PET/CT segmentation models can automate tumor delineation, however, current multimodal models do not fully exploit the complementary information in each modality, as they either concatenate PET and CT data or fuse them at the decision level. To combat this, we propose Mirror U-Net, which replaces traditional fusion methods with multimodal fission by factorizing the multimodal representation into modality-specific branches and an auxiliary multimodal decoder. At these branches, Mirror U-Net assigns a task tailored to each modality to reinforce unimodal features while preserving multimodal features in the shared representation. In contrast to previous methods that use either fission or multi-task learning, Mirror U-Net combines both paradigms in a unified framework. We explore various task combinations and examine which parameters to share in the model. We evaluate Mirror U-Net on the AutoPET PET/CT and on the multimodal MSD BrainTumor datasets, demonstrating its effectiveness in multimodal segmentation and achieving state-of-the-art performance on both datasets. Our code will be made publicly available.

Guiding the Guidance: A Comparative Analysis of User Guidance Signals for Interactive Segmentation of Volumetric Images

Interactive segmentation reduces the annotation time of medical images and allows annotators to iteratively refine labels with corrective interactions, such as clicks. While existing interactive models transform clicks into user guidance signals, which are combined with images to form (image, guidance) pairs, the question of how to best represent the guidance has not been fully explored. To address this, we conduct a comparative study of existing guidance signals by training interactive models with different signals and parameter settings to identify crucial parameters for the model's design. Based on our findings, we design a guidance signal that retains the benefits of other signals while addressing their limitations. We propose an adaptive Gaussian heatmaps guidance signal that utilizes the geodesic distance transform to dynamically adapt the radius of each heatmap when encoding clicks. We conduct our study on the MSD Spleen and the AutoPET datasets to explore the segmentation of both anatomy (spleen) and pathology (tumor lesions). Our results show that choosing the guidance signal is crucial for interactive segmentation as we improve the performance by 14% Dice with our adaptive heatmaps on the challenging AutoPET dataset when compared to non-interactive models. This brings interactive models one step closer to deployment on clinical workflows. We will make our code publically available.

Understanding metric-related pitfalls in image analysis validation

Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation.

Multimodal Interactive Lung Lesion Segmentation: A Framework for Annotating PET/CT Images based on Physiological and Anatomical Cues

Recently, deep learning enabled the accurate segmentation of various diseases in medical imaging. These performances, however, typically demand large amounts of manual voxel annotations. This tedious process for volumetric data becomes more complex when not all required information is available in a single imaging domain as is the case for PET/CT data. We propose a multimodal interactive segmentation framework that mitigates these issues by combining anatomical and physiological cues from PET/CT data. Our framework utilizes the geodesic distance transform to represent the user annotations and we implement a novel ellipsoid-based user simulation scheme during training. We further propose two annotation interfaces and conduct a user study to estimate their usability. We evaluated our model on the in-domain validation dataset and an unseen PET/CT dataset. We make our code publicly available: https://github.com/verena-hallitschke/pet-ct-annotate.