Ramona Woitek

Amirreza Mahbod, Christine Polak, Katharina Feldmann et al.

In computational pathology, automatic nuclei instance segmentation plays an essential role in whole slide image analysis. While many computerized approaches have been proposed for this task, supervised deep learning (DL) methods have shown superior segmentation performances compared to classical machine learning and image processing techniques. However, these models need fully annotated datasets for training which is challenging to acquire, especially in the medical domain. In this work, we release one of the biggest fully manually annotated datasets of nuclei in Hematoxylin and Eosin (H&E)-stained histological images, called NuInsSeg. This dataset contains 665 image patches with more than 30,000 manually segmented nuclei from 31 human and mouse organs. Moreover, for the first time, we provide additional ambiguous area masks for the entire dataset. These vague areas represent the parts of the images where precise and deterministic manual annotations are impossible, even for human experts. The dataset and detailed step-by-step instructions to generate related segmentation masks are publicly available at https://www.kaggle.com/datasets/ipateam/nuinsseg and https://github.com/masih4/NuInsSeg, respectively.

Amirreza Mahbod, Nematollah Saeidi, Sepideh Hatamikia et al.

Medical image retrieval refers to the task of finding similar images for given query images in a database, with applications such as diagnosis support. While traditional medical image retrieval relied on clinical metadata, content-based medical image retrieval (CBMIR) depends on image features, which can be extracted automatically or semi-automatically. Many approaches have been proposed for CBMIR, and among them, using pre-trained convolutional neural networks (CNNs) is a widely utilized approach. However, considering the recent advances in the development of foundation models for various computer vision tasks, their application for CBMIR can also be investigated. In this study, we used several pre-trained feature extractors from well-known pre-trained CNNs and pre-trained foundation models and investigated the CBMIR performance on eight types of two-dimensional (2D) and three-dimensional (3D) medical images. Furthermore, we investigated the effect of image size on the CBMIR performance. Our results show that, overall, for the 2D datasets, foundation models deliver superior performance by a large margin compared to CNNs, with the general-purpose self-supervised model for computational pathology (UNI) providing the best overall performance across all datasets and image sizes. For 3D datasets, CNNs and foundation models deliver more competitive performance, with contrastive learning from captions for histopathology model (CONCH) achieving the best overall performance. Moreover, our findings confirm that while using larger image sizes (especially for 2D datasets) yields slightly better performance, competitive CBMIR performance can still be achieved even with smaller image sizes. Our codes to reproduce the results are available at: https://github.com/masih4/MedImageRetrieval.

Palak Handa, Manas Dhir, Amirreza Mahbod et al.

Computer-based analysis of Wireless Capsule Endoscopy (WCE) is crucial. However, a medically annotated WCE dataset for training and evaluation of automatic classification, detection, and segmentation of bleeding and non-bleeding frames is currently lacking. The present work focused on development of a medically annotated WCE dataset called WCEbleedGen for automatic classification, detection, and segmentation of bleeding and non-bleeding frames. It comprises 2,618 WCE bleeding and non-bleeding frames which were collected from various internet resources and existing WCE datasets. A comprehensive benchmarking and evaluation of the developed dataset was done using nine classification-based, three detection-based, and three segmentation-based deep learning models. The dataset is of high-quality, is class-balanced and contains single and multiple bleeding sites. Overall, our standard benchmark results show that Visual Geometric Group (VGG) 19, You Only Look Once version 8 nano (YOLOv8n), and Link network (Linknet) performed best in automatic classification, detection, and segmentation-based evaluations, respectively. Automatic bleeding diagnosis is crucial for WCE video interpretations. This diverse dataset will aid in developing of real-time, multi-task learning-based innovative solutions for automatic bleeding diagnosis in WCE. The dataset and code are publicly available at https://zenodo.org/records/10156571 and https://github.com/misahub2023/Benchmarking-Codes-of-the-WCEBleedGen-dataset.

Palak Handa, Amirreza Mahbod, Florian Schwarzhans et al.

We present the Capsule Vision 2024 Challenge: Multi-Class Abnormality Classification for Video Capsule Endoscopy. It was virtually organized by the Research Center for Medical Image Analysis and Artificial Intelligence (MIAAI), Department of Medicine, Danube Private University, Krems, Austria in collaboration with the 9th International Conference on Computer Vision & Image Processing (CVIP 2024) being organized by the Indian Institute of Information Technology, Design and Manufacturing (IIITDM) Kancheepuram, Chennai, India. This document provides an overview of the challenge, including the registration process, rules, submission format, description of the datasets used, qualified team rankings, all team descriptions, and the benchmarking results reported by the organizers.

Thomas Buddenkotte, Lorena Escudero Sanchez, Mireia Crispin-Ortuzar et al.

Uncertainty quantification in automated image analysis is highly desired in many applications. Typically, machine learning models in classification or segmentation are only developed to provide binary answers; however, quantifying the uncertainty of the models can play a critical role for example in active learning or machine human interaction. Uncertainty quantification is especially difficult when using deep learning-based models, which are the state-of-the-art in many imaging applications. The current uncertainty quantification approaches do not scale well in high-dimensional real-world problems. Scalable solutions often rely on classical techniques, such as dropout, during inference or training ensembles of identical models with different random seeds to obtain a posterior distribution. In this paper, we show that these approaches fail to approximate the classification probability. On the contrary, we propose a scalable and intuitive framework to calibrate ensembles of deep learning models to produce uncertainty quantification measurements that approximate the classification probability. On unseen test data, we demonstrate improved calibration, sensitivity (in two out of three cases) and precision when being compared with the standard approaches. We further motivate the usage of our method in active learning, creating pseudo-labels to learn from unlabeled images and human-machine collaboration.

Francesca Fati, Felipe Coutinho, Marika Reinius et al.

Purpose. High-grade serous ovarian carcinoma (HGSOC) is characterized by pronounced biological and spatial heterogeneity and is frequently diagnosed at an advanced stage. Neoadjuvant chemotherapy (NACT) followed by delayed primary surgery is commonly employed in patients unsuitable for primary cytoreduction. The Chemotherapy Response Score (CRS) is a validated histopathological biomarker of response to NACT, but it is only available postoperatively. In this study, we investigate whether pre-treatment computed tomography (CT) imaging and clinical data can be used to predict CRS as an investigational decision-support adjunct to inform multidisciplinary team (MDT) discussions regarding expected treatment response. Methods. We proposed a 2.5D multimodal deep learning framework that processes lesion-dense omental slices using a pre-trained Vision Transformer encoder and integrates the resulting visual representations with clinical variables through an intermediate fusion module to predict CRS. Results. Our multimodal model, integrating imaging and clinical data, achieved a ROC-AUC of 0.95 alongside 95% accuracy and 80% precision on the internal test cohort (IEO, n=41 patients). On the external test set (OV04, n=70 patients), it achieved a ROC-AUC of 0.68, alongside 67% accuracy and 75% precision. Conclusion. These preliminary results demonstrate the feasibility of transformer-based deep learning for preoperative prediction of CRS in HGSOC using routine clinical data and CT imaging. As an investigational, pre-treatment decision-support tool, this approach may assist MDT discussions by providing early, non-invasive estimates of treatment response.

Sepideh Hatamikia, Geevarghese George, Florian Schwarzhans et al.

Objectives: High-grade serous ovarian carcinoma (HGSOC) is typically diagnosed at an advanced stage with extensive peritoneal metastases, making treatment challenging. Neoadjuvant chemotherapy (NACT) is often used to reduce tumor burden before surgery, but about 40% of patients show limited response. Radiomics, combined with machine learning (ML), offers a promising non-invasive method for predicting NACT response by analyzing computed tomography (CT) imaging data. This study aimed to improve response prediction in HGSOC patients undergoing NACT by integration different feature selection methods. Materials and methods: A framework for selecting robust radiomics features was introduced by employing an automated randomisation algorithm to mimic inter-observer variability, ensuring a balance between feature robustness and prediction accuracy. Four response metrics were used: chemotherapy response score (CRS), RECIST, volume reduction (VolR), and diameter reduction (DiaR). Lesions in different anatomical sites were studied. Pre- and post-NACT CT scans were used for feature extraction and model training on one cohort, and an independent cohort was used for external testing. Results: The best prediction performance was achieved using all lesions combined for VolR prediction, with an AUC of 0.83. Omental lesions provided the best results for CRS prediction (AUC 0.77), while pelvic lesions performed best for DiaR (AUC 0.76). Conclusion: The integration of robustness into the feature selection processes ensures the development of reliable models and thus facilitates the implementation of the radiomics models in clinical applications for HGSOC patients. Future work should explore further applications of radiomics in ovarian cancer, particularly in real-time clinical settings.

Inês P. Machado, Anna Reithmeir, Fryderyk Kogl et al.

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.

Amirreza Mahbod, Ramona Woitek, Jeanne Shen

In computational pathology, nuclear instance segmentation is a fundamental task with many downstream clinical applications. With the advent of deep learning, many approaches, including convolutional neural networks (CNNs) and vision transformers (ViTs), have been proposed for this task, along with both machine learning-based and non-machine learning-based pre- and post-processing techniques to further boost performance. However, one fundamental aspect that has received less attention is the evaluation pipeline. In this study, we identify four key issues associated with nuclear instance segmentation evaluation and propose corresponding solutions. Our proposed modifications, namely handling vague regions, score normalization, overlapping instances, and border uncertainty, are integrated into a unified framework called NucEval, which enables robust evaluation of nuclear instance segmentation. We evaluate this pipeline using the NuInsSeg dataset, which provides unique characteristics that make it particularly suitable for this study, as well as two additional external datasets, with three CNN- and ViT-based nuclear instance segmentation models, to demonstrate the impact of these modifications on instance segmentation metrics. The code, along with complete guidelines and illustrative examples, is publicly available at: https://github.com/masih4/nuc_eval.

Nima Torbati, Anastasia Meshcheryakova, Ramona Woitek et al.

Melanoma is the most lethal form of skin cancer, with an increasing incidence rate worldwide. Analyzing histological images of melanoma by localizing and classifying tissues and cell nuclei is considered the gold standard method for diagnosis and treatment options for patients. While many computerized approaches have been proposed for automatic analysis, most perform tissue-based analysis and nuclei (cell)-based analysis as separate tasks, which might be suboptimal. In this work, using the PUMA challenge dataset, we propose a novel multi-stage deep learning approach by combining tissue and nuclei information in a unified framework based on the auto-context concept to perform segmentation and classification in histological images of melanoma. Through pre-training and further post-processing, our approach achieved second and first place rankings in the PUMA challenge, with average micro Dice tissue score and summed nuclei F1-score of 73.40% for Track 1 and 63.48% for Track 2, respectively. Furthermore, through a comprehensive ablation study and additional evaluation on an external dataset, we demonstrated the effectiveness of the framework components as well as the generalization capabilities of the proposed approach. Our implementation for training and testing is available at: https://github.com/NimaTorbati/PumaSubmit

Nima Torbati, Anastasia Meshcheryakova, Ramona Woitek et al.

Automated histopathological image analysis plays a vital role in computer-aided diagnosis of various diseases. Among developed algorithms, deep learning-based approaches have demonstrated excellent performance in multiple tasks, including semantic tissue segmentation in histological images. In this study, we propose a novel approach based on attention-driven feature fusion of convolutional neural networks (CNNs) and vision transformers (ViTs) within a unified dual-encoder model to improve semantic segmentation performance. Evaluation on two publicly available datasets showed that our model achieved μIoU/μDice scores of 76.79%/86.87% on the GCPS dataset and 64.93%/76.60% on the PUMA dataset, outperforming state-of-the-art and baseline benchmarks. The implementation of our method is publicly available in a GitHub repository: https://github.com/NimaTorbati/ACS-SegNet

Nematollah Saeidi, Hossein Karshenas, Bijan Shoushtarian et al.

Breast cancer is the most common cancer type in women worldwide. Early detection and appropriate treatment can significantly reduce its impact. While histopathology examinations play a vital role in rapid and accurate diagnosis, they often require experienced medical experts for proper recognition and cancer grading. Automated image retrieval systems have the potential to assist pathologists in identifying cancerous tissues, thereby accelerating the diagnostic process. Nevertheless, proposing an accurate image retrieval model is challenging due to considerable variability among the tissue and cell patterns in histological images. In this work, we leverage the features from foundation models in a novel attention-based adversarially regularized variational graph autoencoder model for breast histological image retrieval. Our results confirm the superior performance of models trained with foundation model features compared to those using pre-trained convolutional neural networks (up to 7.7% and 15.5% for mAP and mMV, respectively), with the pre-trained general-purpose self-supervised model for computational pathology (UNI) delivering the best overall performance. By evaluating two publicly available histology image datasets of breast cancer, our top-performing model, trained with UNI features, achieved average mAP/mMV scores of 96.7%/91.5% and 97.6%/94.2% for the BreakHis and BACH datasets, respectively. Our proposed retrieval model has the potential to be used in clinical settings to enhance diagnostic performance and ultimately benefit patients.

Nima Torbati, Anastasia Meshcheryakova, Ramona Woitek et al.

Nuclei instance segmentation in hematoxylin and eosin (H&E)-stained images plays an important role in automated histological image analysis, with various applications in downstream tasks. While several machine learning and deep learning approaches have been proposed for nuclei instance segmentation, most research in this field focuses on developing new segmentation algorithms and benchmarking them on a limited number of arbitrarily selected public datasets. In this work, rather than focusing on model development, we focused on the datasets used for this task. Based on an extensive literature review, we identified manually annotated, publicly available datasets of H&E-stained images for nuclei instance segmentation and standardized them into a unified input and annotation format. Using two state-of-the-art segmentation models, one based on convolutional neural networks (CNNs) and one based on a hybrid CNN and vision transformer architecture, we systematically evaluated and ranked these datasets based on their nuclei instance segmentation performance. Furthermore, we proposed a unified test set (NucFuse-test) for fair cross-dataset evaluation and a unified training set (NucFuse-train) for improved segmentation performance by merging images from multiple datasets. By evaluating and ranking the datasets, performing comprehensive analyses, generating fused datasets, conducting external validation, and making our implementation publicly available, we provided a new benchmark for training, testing, and evaluating nuclei instance segmentation models on H&E-stained histological images.

Amirreza Mahbod, Rupert Ecker, Ramona Woitek

Accurate classification of skin lesions from dermatoscopic images is essential for diagnosis and treatment of skin cancer. In this study, we investigate the utility of a dermatology-specific foundation model, PanDerm, in comparison with two Vision Transformer (ViT) architectures (ViT base and Swin Transformer V2 base) for the task of skin lesion classification. Using frozen features extracted from PanDerm, we apply non-linear probing with three different classifiers, namely, multi-layer perceptron (MLP), XGBoost, and TabNet. For the ViT-based models, we perform full fine-tuning to optimize classification performance. Our experiments on the HAM10000 and MSKCC datasets demonstrate that the PanDerm-based MLP model performs comparably to the fine-tuned Swin transformer model, while fusion of PanDerm and Swin Transformer predictions leads to further performance improvements. Future work will explore additional foundation models, fine-tuning strategies, and advanced fusion techniques.

Olgica Zaric, Carmen Leser, Vladimir Juras et al.

Introduction: In sodium (23Na) magnetic resonance imaging (MRI), partial volume effects (PVE) are one of the most common causes of errors in the in vivo quantification of tissue sodium concentration (TSC). Advanced image reconstruction algorithms, such as compressed sensing (CS), have the potential to reduce PVE. Therefore, we investigated the feasibility of using CS-based methods to improve image quality and TSC quantification accuracy in patients with breast cancer. Subjects and methods: In this study, three healthy participants and 12 female participants with breast cancer were examined on a 7T MRI scanner. 23Na-MRI images were reconstructed using weighted total variation (wTV), directional total variation (dTV), anatomically guided total variation (AG-TV) and adaptive combine (ADC) methods. The consistency of tumor volume delineations based on sodium data was assessed using the Dice score, and TSC quantification was performed for various image reconstruction methods. Pearsons correlation coefficients were calculated to assess the relationships between wTV, dTV, AG-TV, and ADC values. Results: All methods provided breast MRI images with well-preserved sodium signal and tissue structures. The mean Dice scores for wTV, dTV, and AG-TV were 65%, 72%, and 75%, respectively. Average TSC values in breast tumors were 61.0, 72.0, 73.0, and 88.0 mmol/L for wTV, dTV, AG-TV, and ADC, respectively. A strong negative correlation was observed between wTV and dTV (r = -0.78, 95% CI [-0.94, -0.31], p = 0.0076) and a strong positive correlation between dTV and AG-TV (r = 0.71, 95% CI [0.16, 0.92], p = 0.0207) was found. Conclusion: The results of this study showed that differences in tumor appearance and TSC estimations may depend on the type of image reconstruction and the parameters used. This is most likely due to differences in their ability to reduce PVE.

Muhammad Shahkar Khan, Haider Ali, Laura Villazan Garcia et al.

Background: Multiparametric breast MRI data might improve tumor diagnostics, characterization, and treatment planning. Accurate alignment and delineation of images acquired at different field strengths such as 3T and 7T, remain challenging research tasks. Purpose: To address alignment challenges and enable consistent tumor segmentation across different MRI field strengths. Study type: Retrospective. Subjects: Nine female subjects with breast tumors were involved: six histologically proven invasive ductal carcinomas (IDC) and three fibroadenomas. Field strength/sequence: Imaging was performed at 3T and 7T scanners using post-contrast T1-weighted three-dimensional time-resolved angiography with stochastic trajectories (TWIST) sequence. Assessments: The method's performance for joint image registration and tumor segmentation was evaluated using several quantitative metrics, including signal-to-noise ratio (PSNR), structural similarity index (SSIM), normalized cross-correlation (NCC), Dice coefficient, F1 score, and relative sum of squared differences (rel SSD). Statistical tests: The Pearson correlation coefficient was used to test the relationship between the registration and segmentation metrics. Results: When calculated for each subject individually, the PSNR was in a range from 27.5 to 34.5 dB, and the SSIM was from 82.6 to 92.8%. The model achieved an NCC from 96.4 to 99.3% and a Dice coefficient of 62.9 to 95.3%. The F1 score was between 55.4 and 93.2% and the rel SSD was in the range of 2.0 and 7.5%. The segmentation metrics Dice and F1 Score are highly correlated (0.995), while a moderate correlation between NCC and SSIM (0.681) was found for registration. Data conclusion: Initial results demonstrate that the proposed method may be feasible in providing joint tumor segmentation and registration of MRI data acquired at different field strengths.

Amirreza Mahbod, Georg Dorffner, Isabella Ellinger et al.

With the advent of digital pathology and microscopic systems that can scan and save whole slide histological images automatically, there is a growing trend to use computerized methods to analyze acquired images. Among different histopathological image analysis tasks, nuclei instance segmentation plays a fundamental role in a wide range of clinical and research applications. While many semi- and fully-automatic computerized methods have been proposed for nuclei instance segmentation, deep learning (DL)-based approaches have been shown to deliver the best performances. However, the performance of such approaches usually degrades when tested on unseen datasets. In this work, we propose a novel method to improve the generalization capability of a DL-based automatic segmentation approach. Besides utilizing one of the state-of-the-art DL-based models as a baseline, our method incorporates non-deterministic train time and deterministic test time stain normalization, and ensembling to boost the segmentation performance. We trained the model with one single training set and evaluated its segmentation performance on seven test datasets. Our results show that the proposed method provides up to 4.9%, 5.4%, and 5.9% better average performance in segmenting nuclei based on Dice score, aggregated Jaccard index, and panoptic quality score, respectively, compared to the baseline segmentation model.

Maureen van Eijnatten, Leonardo Rundo, K. Joost Batenburg et al.

This study investigates the use of the unsupervised deep learning framework VoxelMorph for deformable registration of longitudinal abdominopelvic CT images acquired in patients with bone metastases from breast cancer. The CT images were refined prior to registration by automatically removing the CT table and all other extra-corporeal components. To improve the learning capabilities of VoxelMorph when only a limited amount of training data is available, a novel incremental training strategy is proposed based on simulated deformations of consecutive CT images. In a 4-fold cross-validation scheme, the incremental training strategy achieved significantly better registration performance compared to training on a single volume. Although our deformable image registration method did not outperform iterative registration using NiftyReg (considered as a benchmark) in terms of registration quality, the registrations were approximately 300 times faster. This study showed the feasibility of deep learning based deformable registration of longitudinal abdominopelvic CT images via a novel incremental training strategy based on simulated deformations.