Sepideh Hatamikia

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.

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.

Eashrat Jahan Muniya, Gernot Kronreif, Ander Biguri et al.

Soft-tissue deformation remains a major limitation in image-guided neurosurgery, where intra-operative anatomy can deviate substantially from pre-operative imaging due to brain shift, compromising navigation accuracy and surgical safety. Existing compensation methods often rely on intra-operative MRI, CT, or ultrasound, which are disruptive and difficult to integrate repeatedly into the surgical workflow. In contrast, partial 3D cortical surfaces can be reconstructed as point clouds from stereoscopic microscopes or laser range scanners (LRS), capturing only a limited portion of the exposed cortex. This makes point cloud registration a practical alternative without interrupting surgery; however, such partial and noisy observations make deformation estimation highly challenging. In this study, we propose a deep learning-based framework for non-rigid volume-to-surface registration, enabling dense displacement field estimation from sparse intra-operative surface observations without explicit point correspondences or volumetric intra-operative imaging. The network leverages multi-scale point-based feature extraction and a hierarchical deformation decoder to capture both global and local deformations. The key contribution lies in integrating partial intra-operative surface information into the full pre-operative point cloud domain, enabling implicit correspondence learning and dense deformation recovery under limited visibility. Quantitative results demonstrate accurate recovery of fine-scale deformations, achieving an Endpoint Error (EPE) of 1.13 +/- 0.75 mm and RMSE of 1.33 +/- 0.81 mm under challenging partial-surface conditions. The proposed approach supports automatic, workflow-compatible brain-shift compensation from sparse surface observations.

Ali Abbasian Ardakani, Afshin Mohammadi, Alisa Mohebbi et al.

Background: The 2022 update of the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound classification refines risk stratification for adnexal lesions, yet human interpretation remains subject to variability and conservative thresholds. Concurrently, deep learning (DL) models have demonstrated promise in image-based ovarian lesion characterization. This study evaluates radiologist performance applying O-RADS v2022, compares it to leading convolutional neural network (CNN) and Vision Transformer (ViT) models, and investigates the diagnostic gains achieved by hybrid human-AI frameworks. Methods: In this single-center, retrospective cohort study, a total of 512 adnexal mass images from 227 patients (110 with at least one malignant cyst) were included. Sixteen DL models, including DenseNets, EfficientNets, ResNets, VGGs, Xception, and ViTs, were trained and validated. A hybrid model integrating radiologist O-RADS scores with DL-predicted probabilities was also built for each scheme. Results: Radiologist-only O-RADS assessment achieved an AUC of 0.683 and an overall accuracy of 68.0%. CNN models yielded AUCs of 0.620 to 0.908 and accuracies of 59.2% to 86.4%, while ViT16-384 reached the best performance, with an AUC of 0.941 and an accuracy of 87.4%. Hybrid human-AI frameworks further significantly enhanced the performance of CNN models; however, the improvement for ViT models was not statistically significant (P-value >0.05). Conclusions: DL models markedly outperform radiologist-only O-RADS v2022 assessment, and the integration of expert scores with AI yields the highest diagnostic accuracy and discrimination. Hybrid human-AI paradigms hold substantial potential to standardize pelvic ultrasound interpretation, reduce false positives, and improve detection of high-risk lesions.

Poorya MohammadiNasab, Ander Biguri, Philipp Steininger et al.

Iterative reconstruction technique's ability to reduce radiation exposure by using fewer projections has attracted significant attention. However, these methods typically require a precise tuning of several hyperparameters, which can have a major impact on reconstruction quality. Manually setting these parameters is time-consuming and increases the workload for human operators. In this paper, we introduce a novel fully automatic parameter optimization framework that can be applied to a wide range of Cone-beam computed tomography (CBCT) iterative reconstruction algorithms to determine optimal parameters without requiring a reference reconstruction. The proposed method incorporates a modified crow search algorithm (CSA) featuring a superior set-dependent local search mechanism, a search-space-aware global search strategy, and an objective-driven balance between local and global search. Additionally, to ensure an effective initial population, we propose a chaotic diagonal linear uniform initialization scheme that accelerates algorithm convergence. The performance of the proposed framework was evaluated on three imaging machines and four real datasets, as well as three different iterative reconstruction methods with the highest number of tunable parameters, representing the most challenging senario. The results indicate that the proposed method could outperform manual settings and CSA, with an 4.19% improvement in average fitness and 4.89% and 3.82% improvements on CHILL@UK and RPI_AXIS, respectively, which are two benchmark no-reference learning-based quality metrics. In addition, the qualitative results clearly show the superiority of the proposed method by maintaining fine details sharply. The overall performance of the proposed framework across different comparison scenarios demonstrates its effectiveness and robustness across all cases.

Arezoo Borji, Gernot Kronreif, Bernhard Angermayr et al.

Breast cancer is a highly heterogeneous disease with diverse molecular profiles. The PAM50 gene signature is widely recognized as a standard for classifying breast cancer into intrinsic subtypes, enabling more personalized treatment strategies. In this study, we introduce a novel optimization-driven deep learning framework that aims to reduce reliance on costly molecular assays by directly predicting PAM50 subtypes from H&E-stained whole-slide images (WSIs). Our method jointly optimizes patch informativeness, spatial diversity, uncertainty, and patch count by combining the non-dominated sorting genetic algorithm II (NSGA-II) with Monte Carlo dropout-based uncertainty estimation. The proposed method can identify a small but highly informative patch subset for classification. We used a ResNet18 backbone for feature extraction and a custom CNN head for classification. For evaluation, we used the internal TCGA-BRCA dataset as the training cohort and the external CPTAC-BRCA dataset as the test cohort. On the internal dataset, an F1-score of 0.8812 and an AUC of 0.9841 using 627 WSIs from the TCGA-BRCA cohort were achieved. The performance of the proposed approach on the external validation dataset showed an F1-score of 0.7952 and an AUC of 0.9512. These findings indicate that the proposed optimization-guided, uncertainty-aware patch selection can achieve high performance and improve the computational efficiency of histopathology-based PAM50 classification compared to existing methods, suggesting a scalable imaging-based replacement that has the potential to support clinical decision-making.

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

Ansar Rahman, Hassan Shojaee-Mend, Sepideh Hatamikia

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by atypical functional brain connectivity and subtle structural alterations. rs-fMRI has been widely used to identify disruptions in large-scale brain networks, while structural MRI provides complementary information about morphological organization. Despite their complementary nature, effectively integrating these heterogeneous imaging modalities within a unified framework remains challenging. This study proposes a multimodal graph learning framework that preserves the dominant role of functional connectivity while integrating structural imaging and phenotypic information for ASD classification. The proposed framework is evaluated on ABIDE-I dataset. Each subject is represented as a node within a population graph. Functional and structural features are extracted as modality-specific node attributes, while inter-subject relationships are modeled using a pairwise association encoder (PAE) based on phenotypic information. Two Edge Variational GCNs are trained to learn subject-level embeddings. To enable effective multimodal integration, we introduce a novel asymmetric transformer-based cross-attention mechanism that allows functional embeddings to selectively incorporate complementary structural information while preserving functional dominance. The fused embeddings are then passed to a MLP for ASD classification. Using stratified 10-fold cross-validation, the framework achieved an AUC of 87.3% and an accuracy of 84.4%. Under leave-one-site-out cross-validation (LOSO-CV), the model achieved an average cross-site accuracy of 82.0%, outperforming existing methods by approximately 3% under 10-fold cross-validation and 7% under LOSO-CV. The proposed framework effectively integrates heterogeneous multimodal data from the multi-site ABIDE-I dataset, improving automated ASD classification across imaging sites.

Arezoo Borji, Gernot Kronreif, Bernhard Angermayr et al.

Recent advances in machine learning are transforming medical image analysis, particularly in cancer detection and classification. Techniques such as deep learning, especially convolutional neural networks (CNNs) and vision transformers (ViTs), are now enabling the precise analysis of complex histopathological images, automating detection, and enhancing classification accuracy across various cancer types. This study focuses on osteosarcoma (OS), the most common bone cancer in children and adolescents, which affects the long bones of the arms and legs. Early and accurate detection of OS is essential for improving patient outcomes and reducing mortality. However, the increasing prevalence of cancer and the demand for personalized treatments create challenges in achieving precise diagnoses and customized therapies. We propose a novel hybrid model that combines convolutional neural networks (CNN) and vision transformers (ViT) to improve diagnostic accuracy for OS using hematoxylin and eosin (H&E) stained histopathological images. The CNN model extracts local features, while the ViT captures global patterns from histopathological images. These features are combined and classified using a Multi-Layer Perceptron (MLP) into four categories: non-tumor (NT), non-viable tumor (NVT), viable tumor (VT), and none-viable ratio (NVR). Using the Cancer Imaging Archive (TCIA) dataset, the model achieved an accuracy of 99.08%, precision of 99.10%, recall of 99.28%, and an F1-score of 99.23%. This is the first successful four-class classification using this dataset, setting a new benchmark in OS research and offering promising potential for future diagnostic advancements.

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.

Ali Abbasian Ardakani, Afshin Mohammadi, Taha Yusuf Kuzan et al.

To develop and externally validate integrated ultrasound nomograms combining BIRADS features and quantitative morphometric characteristics, and to compare their performance with expert radiologists and state of the art large language models in biopsy recommendation and malignancy prediction for breast lesions. In this retrospective multicenter, multinational study, 1747 women with pathologically confirmed breast lesions underwent ultrasound across three centers in Iran and Turkey. A total of 10 BIRADS and 26 morphological features were extracted from each lesion. A BIRADS, morphometric, and fused nomogram integrating both feature sets was constructed via logistic regression. Three radiologists (one senior, two general) and two ChatGPT variants independently interpreted deidentified breast lesion images. Diagnostic performance for biopsy recommendation (BIRADS 4,5) and malignancy prediction was assessed in internal and two external validation cohorts. In pooled analysis, the fused nomogram achieved the highest accuracy for biopsy recommendation (83.0%) and malignancy prediction (83.8%), outperforming the morphometric nomogram, three radiologists and both ChatGPT models. Its AUCs were 0.901 and 0.853 for the two tasks, respectively. In addition, the performance of the BIRADS nomogram was significantly higher than the morphometric nomogram, three radiologists and both ChatGPT models for biopsy recommendation and malignancy prediction. External validation confirmed the robust generalizability across different ultrasound platforms and populations. An integrated BIRADS morphometric nomogram consistently outperforms standalone models, LLMs, and radiologists in guiding biopsy decisions and predicting malignancy. These interpretable, externally validated tools have the potential to reduce unnecessary biopsies and enhance personalized decision making in breast imaging.

Arezoo Borji, Hossam Haick, Birgit Pohn et al.

In vitro fertilization (IVF) is a widely utilized assisted reproductive technology, yet predicting its success remains challenging due to the multifaceted interplay of clinical, demographic, and procedural factors. This study develops a robust artificial intelligence (AI) pipeline aimed at predicting live birth outcomes in IVF treatments. The pipeline uses anonymized data from 2010 to 2018, obtained from the Human Fertilization and Embryology Authority (HFEA). We evaluated the prediction performance of live birth success as a binary outcome (success/failure) by integrating different feature selection methods, such as principal component analysis (PCA) and particle swarm optimization (PSO), with different traditional machine learning-based classifiers including random forest (RF) and decision tree, as well as deep learning-based classifiers including custom transformer-based model and a tab transformer model with an attention mechanism. Our research demonstrated that the best performance was achieved by combining PSO for feature selection with the TabTransformer-based deep learning model, yielding an accuracy of 99.50% and an AUC of 99.96%, highlighting its significant performance to predict live births. This study establishes a highly accurate AI pipeline for predicting live birth outcomes in IVF, demonstrating its potential to enhance personalized fertility treatments.

Jana Zakall, Birgit Pohn, Antonia Graf et al.

Artificial intelligence (AI) has emerged as a powerful tool to enhance decision-making and optimize treatment protocols in in vitro fertilization (IVF). In particular, AI shows significant promise in supporting decision-making during the ovarian stimulation phase of the IVF process. This review evaluates studies focused on the applications of AI combined with medical imaging in ovarian stimulation, examining methodologies, outcomes, and current limitations. Our analysis of 13 studies on this topic reveals that, reveal that while AI algorithms demonstrated notable potential in predicting optimal hormonal dosages, trigger timing, and oocyte retrieval outcomes, the medical imaging data utilized predominantly came from two-dimensional (2D) ultrasound which mainly involved basic quantifications, such as follicle size and number, with limited use of direct feature extraction or advanced image analysis techniques. This points to an underexplored opportunity where advanced image analysis approaches, such as deep learning, and more diverse imaging modalities, like three-dimensional (3D) ultrasound, could unlock deeper insights. Additionally, the lack of explainable AI (XAI) in most studies raises concerns about the transparency and traceability of AI-driven decisions - key factors for clinical adoption and trust. Furthermore, many studies relied on single-center designs and small datasets, which limit the generalizability of their findings. This review highlights the need for integrating advanced imaging analysis techniques with explainable AI methodologies, as well as the importance of leveraging multicenter collaborations and larger datasets. Addressing these gaps has the potential to enhance ovarian stimulation management, paving the way for efficient, personalized, and data-driven treatment pathways that improve IVF outcomes.

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.