arXiv subjects

Katharina Breininger

Publications and source records attributed to Katharina Breininger.

At least 55 records · Page 3Linked to original sources

arXiv2023

Adaptive Region Selection for Active Learning in Whole Slide Image Semantic Segmentation

The process of annotating histological gigapixel-sized whole slide images (WSIs) at the pixel level for the purpose of training a supervised segmentation model is time-consuming. Region-based active learning (AL) involves training the model on a limited number of annotated image regions instead of requesting annotations of the entire images. These annotation regions are iteratively selected, with the goal of optimizing model performance while minimizing the annotated area. The standard method for region selection evaluates the informativeness of all square regions of a specified size and then selects a specific quantity of the most informative regions. We find that the efficiency of this method highly depends on the choice of AL step size (i.e., the combination of region size and the number of selected regions per WSI), and a suboptimal AL step size can result in redundant annotation requests or inflated computation costs. This paper introduces a novel technique for selecting annotation regions adaptively, mitigating the reliance on this AL hyperparameter. Specifically, we dynamically determine each region by first identifying an informative area and then detecting its optimal bounding box, as opposed to selecting regions of a uniform predefined shape and size as in the standard method. We evaluate our method using the task of breast cancer metastases segmentation on the public CAMELYON16 dataset and show that it consistently achieves higher sampling efficiency than the standard method across various AL step sizes. With only 2.6\% of tissue area annotated, we achieve full annotation performance and thereby substantially reduce the costs of annotating a WSI dataset. The source code is available at https://github.com/DeepMicroscopy/AdaptiveRegionSelection.

cs.CV↗

arXiv2023

Multi-Scanner Canine Cutaneous Squamous Cell Carcinoma Histopathology Dataset

In histopathology, scanner-induced domain shifts are known to impede the performance of trained neural networks when tested on unseen data. Multi-domain pre-training or dedicated domain-generalization techniques can help to develop domain-agnostic algorithms. For this, multi-scanner datasets with a high variety of slide scanning systems are highly desirable. We present a publicly available multi-scanner dataset of canine cutaneous squamous cell carcinoma histopathology images, composed of 44 samples digitized with five slide scanners. This dataset provides local correspondences between images and thereby isolates the scanner-induced domain shift from other inherent, e.g. morphology-induced domain shifts. To highlight scanner differences, we present a detailed evaluation of color distributions, sharpness, and contrast of the individual scanner subsets. Additionally, to quantify the inherent scanner-induced domain shift, we train a tumor segmentation network on each scanner subset and evaluate the performance both in- and cross-domain. We achieve a class-averaged in-domain intersection over union coefficient of up to 0.86 and observe a cross-domain performance decrease of up to 0.38, which confirms the inherent domain shift of the presented dataset and its negative impact on the performance of deep neural networks.

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arXiv2023

Attention-based Multiple Instance Learning for Survival Prediction on Lung Cancer Tissue Microarrays

Attention-based multiple instance learning (AMIL) algorithms have proven to be successful in utilizing gigapixel whole-slide images (WSIs) for a variety of different computational pathology tasks such as outcome prediction and cancer subtyping problems. We extended an AMIL approach to the task of survival prediction by utilizing the classical Cox partial likelihood as a loss function, converting the AMIL model into a nonlinear proportional hazards model. We applied the model to tissue microarray (TMA) slides of 330 lung cancer patients. The results show that AMIL approaches can handle very small amounts of tissue from a TMA and reach similar C-index performance compared to established survival prediction methods trained with highly discriminative clinical factors such as age, cancer grade, and cancer stage

cs.CV↗

arXiv2022

Deep Learning-Based Automatic Assessment of AgNOR-scores in Histopathology Images

Nucleolar organizer regions (NORs) are parts of the DNA that are involved in RNA transcription. Due to the silver affinity of associated proteins, argyrophilic NORs (AgNORs) can be visualized using silver-based staining. The average number of AgNORs per nucleus has been shown to be a prognostic factor for predicting the outcome of many tumors. Since manual detection of AgNORs is laborious, automation is of high interest. We present a deep learning-based pipeline for automatically determining the AgNOR-score from histopathological sections. An additional annotation experiment was conducted with six pathologists to provide an independent performance evaluation of our approach. Across all raters and images, we found a mean squared error of 0.054 between the AgNOR- scores of the experts and those of the model, indicating that our approach offers performance comparable to humans.

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arXiv2022

Deep learning-based Subtyping of Atypical and Normal Mitoses using a Hierarchical Anchor-Free Object Detector

Mitotic activity is key for the assessment of malignancy in many tumors. Moreover, it has been demonstrated that the proportion of abnormal mitosis to normal mitosis is of prognostic significance. Atypical mitotic figures (MF) can be identified morphologically as having segregation abnormalities of the chromatids. In this work, we perform, for the first time, automatic subtyping of mitotic figures into normal and atypical categories according to characteristic morphological appearances of the different phases of mitosis. Using the publicly available MIDOG21 and TUPAC16 breast cancer mitosis datasets, two experts blindly subtyped mitotic figures into five morphological categories. Further, we set up a state-of-the-art object detection pipeline extending the anchor-free FCOS approach with a gated hierarchical subclassification branch. Our labeling experiment indicated that subtyping of mitotic figures is a challenging task and prone to inter-rater disagreement, which we found in 24.89% of MF. Using the more diverse MIDOG21 dataset for training and TUPAC16 for testing, we reached a mean overall average precision score of 0.552, a ROC AUC score of 0.833 for atypical/normal MF and a mean class-averaged ROC-AUC score of 0.977 for discriminating the different phases of cells undergoing mitosis.

cs.CV↗

arXiv2022

Mind the Gap: Scanner-induced domain shifts pose challenges for representation learning in histopathology

Computer-aided systems in histopathology are often challenged by various sources of domain shift that impact the performance of these algorithms considerably. We investigated the potential of using self-supervised pre-training to overcome scanner-induced domain shifts for the downstream task of tumor segmentation. For this, we present the Barlow Triplets to learn scanner-invariant representations from a multi-scanner dataset with local image correspondences. We show that self-supervised pre-training successfully aligned different scanner representations, which, interestingly only results in a limited benefit for our downstream task. We thereby provide insights into the influence of scanner characteristics for downstream applications and contribute to a better understanding of why established self-supervised methods have not yet shown the same success on histopathology data as they have for natural images.

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arXiv2022

Improved HER2 Tumor Segmentation with Subtype Balancing using Deep Generative Networks

Tumor segmentation in histopathology images is often complicated by its composition of different histological subtypes and class imbalance. Oversampling subtypes with low prevalence features is not a satisfactory solution since it eventually leads to overfitting. We propose to create synthetic images with semantically-conditioned deep generative networks and to combine subtype-balanced synthetic images with the original dataset to achieve better segmentation performance. We show the suitability of Generative Adversarial Networks (GANs) and especially diffusion models to create realistic images based on subtype-conditioning for the use case of HER2-stained histopathology. Additionally, we show the capability of diffusion models to conditionally inpaint HER2 tumor areas with modified subtypes. Combining the original dataset with the same amount of diffusion-generated images increased the tumor Dice score from 0.833 to 0.854 and almost halved the variance between the HER2 subtype recalls. These results create the basis for more reliable automatic HER2 analysis with lower performance variance between individual HER2 subtypes.

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arXiv2022

Employing Graph Representations for Cell-level Characterization of Melanoma MELC Samples

Histopathology imaging is crucial for the diagnosis and treatment of skin diseases. For this reason, computer-assisted approaches have gained popularity and shown promising results in tasks such as segmentation and classification of skin disorders. However, collecting essential data and sufficiently high-quality annotations is a challenge. This work describes a pipeline that uses suspected melanoma samples that have been characterized using Multi-Epitope-Ligand Cartography (MELC). This cellular-level tissue characterisation is then represented as a graph and used to train a graph neural network. This imaging technology, combined with the methodology proposed in this work, achieves a classification accuracy of 87%, outperforming existing approaches by 10%.

cs.CV↗

arXiv2022

A Spatiotemporal Model for Precise and Efficient Fully-automatic 3D Motion Correction in OCT

Optical coherence tomography (OCT) is a micrometer-scale, volumetric imaging modality that has become a clinical standard in ophthalmology. OCT instruments image by raster-scanning a focused light spot across the retina, acquiring sequential cross-sectional images to generate volumetric data. Patient eye motion during the acquisition poses unique challenges: Non-rigid, discontinuous distortions can occur, leading to gaps in data and distorted topographic measurements. We present a new distortion model and a corresponding fully-automatic, reference-free optimization strategy for computational motion correction in orthogonally raster-scanned, retinal OCT volumes. Using a novel, domain-specific spatiotemporal parametrization of forward-warping displacements, eye motion can be corrected continuously for the first time. Parameter estimation with temporal regularization improves robustness and accuracy over previous spatial approaches. We correct each A-scan individually in 3D in a single mapping, including repeated acquisitions used in OCT angiography protocols. Specialized 3D forward image warping reduces median runtime to < 9 s, fast enough for clinical use. We present a quantitative evaluation on 18 subjects with ocular pathology and demonstrate accurate correction during microsaccades. Transverse correction is limited only by ocular tremor, whereas submicron repeatability is achieved axially (0.51 um median of medians), representing a dramatic improvement over previous work. This allows assessing longitudinal changes in focal retinal pathologies as a marker of disease progression or treatment response, and promises to enable multiple new capabilities such as supersampled/super-resolution volume reconstruction and analysis of pathological eye motion occuring in neurological diseases.

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arXiv2022

Pan-tumor CAnine cuTaneous Cancer Histology (CATCH) dataset

Due to morphological similarities, the differentiation of histologic sections of cutaneous tumors into individual subtypes can be challenging. Recently, deep learning-based approaches have proven their potential for supporting pathologists in this regard. However, many of these supervised algorithms require a large amount of annotated data for robust development. We present a publicly available dataset of 350 whole slide images of seven different canine cutaneous tumors complemented by 12,424 polygon annotations for 13 histologic classes, including seven cutaneous tumor subtypes. In inter-rater experiments, we show a high consistency of the provided labels, especially for tumor annotations. We further validate the dataset by training a deep neural network for the task of tissue segmentation and tumor subtype classification. We achieve a class-averaged Jaccard coefficient of 0.7047, and 0.9044 for tumor in particular. For classification, we achieve a slide-level accuracy of 0.9857. Since canine cutaneous tumors possess various histologic homologies to human tumors the added value of this dataset is not limited to veterinary pathology but extends to more general fields of application.

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arXiv2022

PoCaP Corpus: A Multimodal Dataset for Smart Operating Room Speech Assistant using Interventional Radiology Workflow Analysis

This paper presents a new multimodal interventional radiology dataset, called PoCaP (Port Catheter Placement) Corpus. This corpus consists of speech and audio signals in German, X-ray images, and system commands collected from 31 PoCaP interventions by six surgeons with average duration of 81.4 $\pm$ 41.0 minutes. The corpus aims to provide a resource for developing a smart speech assistant in operating rooms. In particular, it may be used to develop a speech controlled system that enables surgeons to control the operation parameters such as C-arm movements and table positions. In order to record the dataset, we acquired consent by the institutional review board and workers council in the University Hospital Erlangen and by the patients for data privacy. We describe the recording set-up, data structure, workflow and preprocessing steps, and report the first PoCaP Corpus speech recognition analysis results with 11.52 $\%$ word error rate using pretrained models. The findings suggest that the data has the potential to build a robust command recognition system and will allow the development of a novel intervention support systems using speech and image processing in the medical domain.

cs.SD↗

arXiv2022

Mitosis domain generalization in histopathology images -- The MIDOG challenge

The density of mitotic figures within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of mitotic figures by pathologists is known to be subject to a strong inter-rater bias, which limits the prognostic value. State-of-the-art deep learning methods can support the expert in this assessment but are known to strongly deteriorate when applied in a different clinical environment than was used for training. One decisive component in the underlying domain shift has been identified as the variability caused by using different whole slide scanners. The goal of the MICCAI MIDOG 2021 challenge has been to propose and evaluate methods that counter this domain shift and derive scanner-agnostic mitosis detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As a test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were given. The best approaches performed on an expert level, with the winning algorithm yielding an F_1 score of 0.748 (CI95: 0.704-0.781). In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance.

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arXiv2022

Domain Adversarial RetinaNet as a Reference Algorithm for the MItosis DOmain Generalization Challenge

Assessing the Mitotic Count has a known high degree of intra- and inter-rater variability. Computer-aided systems have proven to decrease this variability and reduce labeling time. These systems, however, are generally highly dependent on their training domain and show poor applicability to unseen domains. In histopathology, these domain shifts can result from various sources, including different slide scanning systems used to digitize histologic samples. The MItosis DOmain Generalization challenge focused on this specific domain shift for the task of mitotic figure detection. This work presents a mitotic figure detection algorithm developed as a baseline for the challenge, based on domain adversarial training. On the challenge's test set, the algorithm scored an F$_1$ score of 0.7183. The corresponding network weights and code for implementing the network are made publicly available.

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arXiv2022

CAD-RADS Scoring using Deep Learning and Task-Specific Centerline Labeling

With coronary artery disease (CAD) persisting to be one of the leading causes of death worldwide, interest in supporting physicians with algorithms to speed up and improve diagnosis is high. In clinical practice, the severeness of CAD is often assessed with a coronary CT angiography (CCTA) scan and manually graded with the CAD-Reporting and Data System (CAD-RADS) score. The clinical questions this score assesses are whether patients have CAD or not (rule-out) and whether they have severe CAD or not (hold-out). In this work, we reach new state-of-the-art performance for automatic CAD-RADS scoring. We propose using severity-based label encoding, test time augmentation (TTA) and model ensembling for a task-specific deep learning architecture. Furthermore, we introduce a novel task- and model-specific, heuristic coronary segment labeling, which subdivides coronary trees into consistent parts across patients. It is fast, robust, and easy to implement. We were able to raise the previously reported area under the receiver operating characteristic curve (AUC) from 0.914 to 0.942 in the rule-out and from 0.921 to 0.950 in the hold-out task respectively.

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arXiv2022

Automatic Classification of Neuromuscular Diseases in Children Using Photoacoustic Imaging

Neuromuscular diseases (NMDs) cause a significant burden for both healthcare systems and society. They can lead to severe progressive muscle weakness, muscle degeneration, contracture, deformity and progressive disability. The NMDs evaluated in this study often manifest in early childhood. As subtypes of disease, e.g. Duchenne Muscular Dystropy (DMD) and Spinal Muscular Atrophy (SMA), are difficult to differentiate at the beginning and worsen quickly, fast and reliable differential diagnosis is crucial. Photoacoustic and ultrasound imaging has shown great potential to visualize and quantify the extent of different diseases. The addition of automatic classification of such image data could further improve standard diagnostic procedures. We compare deep learning-based 2-class and 3-class classifiers based on VGG16 for differentiating healthy from diseased muscular tissue. This work shows promising results with high accuracies above 0.86 for the 3-class problem and can be used as a proof of concept for future approaches for earlier diagnosis and therapeutic monitoring of NMDs.

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arXiv2022

Initial Investigations Towards Non-invasive Monitoring of Chronic Wound Healing Using Deep Learning and Ultrasound Imaging

Chronic wounds including diabetic and arterial/venous insufficiency injuries have become a major burden for healthcare systems worldwide. Demographic changes suggest that wound care will play an even bigger role in the coming decades. Predicting and monitoring response to therapy in wound care is currently largely based on visual inspection with little information on the underlying tissue. Thus, there is an urgent unmet need for innovative approaches that facilitate personalized diagnostics and treatments at the point-of-care. It has been recently shown that ultrasound imaging can monitor response to therapy in wound care, but this work required onerous manual image annotations. In this study, we present initial results of a deep learning-based automatic segmentation of cross-sectional wound size in ultrasound images and identify requirements and challenges for future research on this application. Evaluation of the segmentation results underscores the potential of the proposed deep learning approach to complement non-invasive imaging with Dice scores of 0.34 (U-Net, FCN) and 0.27 (ResNet-U-Net) but also highlights the need for improving robustness further. We conclude that deep learning-supported analysis of non-invasive ultrasound images is a promising area of research to automatically extract cross-sectional wound size and depth information with potential value in monitoring response to therapy.

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arXiv2022

Superpixel Pre-Segmentation of HER2 Slides for Efficient Annotation

Supervised deep learning has shown state-of-the-art performance for medical image segmentation across different applications, including histopathology and cancer research; however, the manual annotation of such data is extremely laborious. In this work, we explore the use of superpixel approaches to compute a pre-segmentation of HER2 stained images for breast cancer diagnosis that facilitates faster manual annotation and correction in a second step. Four methods are compared: Standard Simple Linear Iterative Clustering (SLIC) as a baseline, a domain adapted SLIC, and superpixels based on feature embeddings of a pretrained ResNet-50 and a denoising autoencoder. To tackle oversegmentation, we propose to hierarchically merge superpixels, based on their content in the respective feature space. When evaluating the approaches on fully manually annotated images, we observe that the autoencoder-based superpixels achieve a 23% increase in boundary F1 score compared to the baseline SLIC superpixels. Furthermore, the boundary F1 score increases by 73% when hierarchical clustering is applied on the adapted SLIC and the autoencoder-based superpixels. These evaluations show encouraging first results for a pre-segmentation for efficient manual refinement without the need for an initial set of annotated training data.

cs.CV↗

arXiv2022

First steps on Gamification of Lung Fluid Cells Annotations in the Flower Domain

Annotating data, especially in the medical domain, requires expert knowledge and a lot of effort. This limits the amount and/or usefulness of available medical data sets for experimentation. Therefore, developing strategies to increase the number of annotations while lowering the needed domain knowledge is of interest. A possible strategy is the use of gamification, i.e. transforming the annotation task into a game. We propose an approach to gamify the task of annotating lung fluid cells from pathological whole slide images (WSIs). As the domain is unknown to non-expert annotators, we transform images of cells to the domain of flower images using a CycleGAN architecture. In this more assessable domain, non-expert annotators can be (t)asked to annotate different kinds of flowers in a playful setting. In order to provide a proof of concept, this work shows that the domain transfer is possible by evaluating an image classification network trained on real cell images and tested on the cell images generated by the CycleGAN network (reconstructed cell images) as well as real cell images. The classification network reaches an average accuracy of 94.73 % on the original lung fluid cells and 95.25 % on the transformed lung fluid cells, respectively. Our study lays the foundation for future research on gamification using CycleGANs.

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