Mostafa Jahanifar

Trinh Thi Le Vuong, Quoc Dang Vu, Mostafa Jahanifar et al.

The appearance of histopathology images depends on tissue type, staining and digitization procedure. These vary from source to source and are the potential causes for domain-shift problems. Owing to this problem, despite the great success of deep learning models in computational pathology, a model trained on a specific domain may still perform sub-optimally when we apply them to another domain. To overcome this, we propose a new augmentation called PatchShuffling and a novel self-supervised contrastive learning framework named IMPaSh for pre-training deep learning models. Using these, we obtained a ResNet50 encoder that can extract image representation resistant to domain-shift. We compared our derived representation against those acquired based on other domain-generalization techniques by using them for the cross-domain classification of colorectal tissue images. We show that the proposed method outperforms other traditional histology domain-adaptation and state-of-the-art self-supervised learning methods. Code is available at: https://github.com/trinhvg/IMPash .

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al.

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

Marc Aubreville, Nikolas Stathonikos, Christof A. Bertram et al.

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.

Simon Graham, Quoc Dang Vu, Mostafa Jahanifar et al.

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

Marc Aubreville, Nikolas Stathonikos, Taryn A. Donovan et al.

Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert consensus and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an $F_1$ score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. However, we also found that domain characteristics not present in the training set (feline as new species, spindle cell shape as new morphology and a new scanner) led to small but significant decreases in performance. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, but with only minor changes in the order of participants in the ranking.

Mostafa Jahanifar, Manahil Raza, Kesi Xu et al.

Deep learning models have exhibited exceptional effectiveness in Computational Pathology (CPath) by tackling intricate tasks across an array of histology image analysis applications. Nevertheless, the presence of out-of-distribution data (stemming from a multitude of sources such as disparate imaging devices and diverse tissue preparation methods) can cause \emph{domain shift} (DS). DS decreases the generalization of trained models to unseen datasets with slightly different data distributions, prompting the need for innovative \emph{domain generalization} (DG) solutions. Recognizing the potential of DG methods to significantly influence diagnostic and prognostic models in cancer studies and clinical practice, we present this survey along with guidelines on achieving DG in CPath. We rigorously define various DS types, systematically review and categorize existing DG approaches and resources in CPath, and provide insights into their advantages, limitations, and applicability. We also conduct thorough benchmarking experiments with 28 cutting-edge DG algorithms to address a complex DG problem. Our findings suggest that careful experiment design and CPath-specific Stain Augmentation technique can be very effective. However, there is no one-size-fits-all solution for DG in CPath. Therefore, we establish clear guidelines for detecting and managing DS depending on different scenarios. While most of the concepts, guidelines, and recommendations are given for applications in CPath, we believe that they are applicable to most medical image analysis tasks as well.

Mostafa Jahanifar, Adam Shephard, Neda Zamanitajeddin et al.

Counting of mitotic figures is a fundamental step in grading and prognostication of several cancers. However, manual mitosis counting is tedious and time-consuming. In addition, variation in the appearance of mitotic figures causes a high degree of discordance among pathologists. With advances in deep learning models, several automatic mitosis detection algorithms have been proposed but they are sensitive to {\em domain shift} often seen in histology images. We propose a robust and efficient two-stage mitosis detection framework, which comprises mitosis candidate segmentation ({\em Detecting Fast}) and candidate refinement ({\em Detecting Slow}) stages. The proposed candidate segmentation model, termed \textit{EUNet}, is fast and accurate due to its architectural design. EUNet can precisely segment candidates at a lower resolution to considerably speed up candidate detection. Candidates are then refined using a deeper classifier network, EfficientNet-B7, in the second stage. We make sure both stages are robust against domain shift by incorporating domain generalization methods. We demonstrate state-of-the-art performance and generalizability of the proposed model on the three largest publicly available mitosis datasets, winning the two mitosis domain generalization challenge contests (MIDOG21 and MIDOG22). Finally, we showcase the utility of the proposed algorithm by processing the TCGA breast cancer cohort (1,125 whole-slide images) to generate and release a repository of more than 620K mitotic figures.

Adam J Shephard, Raja Muhammad Saad Bashir, Hanya Mahmood et al.

Oral epithelial dysplasia (OED) is a premalignant histopathological diagnosis given to lesions of the oral cavity. Its grading suffers from significant inter-/intra- observer variability, and does not reliably predict malignancy progression, potentially leading to suboptimal treatment decisions. To address this, we developed a novel artificial intelligence algorithm that can assign an Oral Malignant Transformation (OMT) risk score, based on histological patterns in the in Haematoxylin and Eosin stained whole slide images, to quantify the risk of OED progression. The algorithm is based on the detection and segmentation of nuclei within (and around) the epithelium using an in-house segmentation model. We then employed a shallow neural network fed with interpretable morphological/spatial features, emulating histological markers. We conducted internal cross-validation on our development cohort (Sheffield; n = 193 cases) followed by independent validation on two external cohorts (Birmingham and Belfast; n = 92 cases). The proposed OMTscore yields an AUROC = 0.74 in predicting whether an OED progresses to malignancy or not. Survival analyses showed the prognostic value of our OMTscore for predicting malignancy transformation, when compared to the manually-assigned WHO and binary grades. Analysis of the correctly predicted cases elucidated the presence of peri-epithelial and epithelium-infiltrating lymphocytes in the most predictive patches of cases that transformed (p < 0.0001). This is the first study to propose a completely automated algorithm for predicting OED transformation based on interpretable nuclear features, whilst being validated on external datasets. The algorithm shows better-than-human-level performance for prediction of OED malignant transformation and offers a promising solution to the challenges of grading OED in routine clinical practice.

Adam Shephard, Mostafa Jahanifar, Ruoyu Wang et al.

The quantification of tumor-infiltrating lymphocytes (TILs) has been shown to be an independent predictor for prognosis of breast cancer patients. Typically, pathologists give an estimate of the proportion of the stromal region that contains TILs to obtain a TILs score. The Tumor InfiltratinG lymphocytes in breast cancER (TiGER) challenge, aims to assess the prognostic significance of computer-generated TILs scores for predicting survival as part of a Cox proportional hazards model. For this challenge, as the TIAger team, we have developed an algorithm to first segment tumor vs. stroma, before localising the tumor bulk region for TILs detection. Finally, we use these outputs to generate a TILs score for each case. On preliminary testing, our approach achieved a tumor-stroma weighted Dice score of 0.791 and a FROC score of 0.572 for lymphocytic detection. For predicting survival, our model achieved a C-index of 0.719. These results achieved first place across the preliminary testing leaderboards of the TiGER challenge.

Quoc Dang Vu, Robert Jewsbury, Simon Graham et al.

Since the introduction of digital and computational pathology as a field, one of the major problems in the clinical application of algorithms has been the struggle to generalize well to examples outside the distribution of the training data. Existing work to address this in both pathology and natural images has focused almost exclusively on classification tasks. We explore and evaluate the robustness of the 7 best performing nuclear segmentation and classification models from the largest computational pathology challenge for this problem to date, the CoNIC challenge. We demonstrate that existing state-of-the-art (SoTA) models are robust towards compression artifacts but suffer substantial performance reduction when subjected to shifts in the color domain. We find that using stain normalization to address the domain shift problem can be detrimental to the model performance. On the other hand, neural style transfer is more consistent in improving test performance when presented with large color variations in the wild.

Neda Zamanitajeddin, Mostafa Jahanifar, Kesi Xu et al.

Deep learning models have shown immense promise in computational pathology (CPath) tasks, but their performance often suffers when applied to unseen data due to domain shifts. Addressing this requires domain generalization (DG) algorithms. However, a systematic evaluation of DG algorithms in the CPath context is lacking. This study aims to benchmark the effectiveness of 30 DG algorithms on 3 CPath tasks of varying difficulty through 7,560 cross-validation runs. We evaluate these algorithms using a unified and robust platform, incorporating modality-specific techniques and recent advances like pretrained foundation models. Our extensive cross-validation experiments provide insights into the relative performance of various DG strategies. We observe that self-supervised learning and stain augmentation consistently outperform other methods, highlighting the potential of pretrained models and data augmentation. Furthermore, we introduce a new pan-cancer tumor detection dataset (HISTOPANTUM) as a benchmark for future research. This study offers valuable guidance to researchers in selecting appropriate DG approaches for CPath tasks.

Adam J Shephard, Mostafa Jahanifar, Ruoyu Wang et al.

Tumour-infiltrating lymphocytes (TILs) are considered as a valuable prognostic markers in both triple-negative and human epidermal growth factor receptor 2 (HER2) positive breast cancer. In this study, we introduce an innovative deep learning pipeline based on the Efficient-UNet architecture to predict the TILs score for breast cancer whole-slide images (WSIs). We first segment tumour and stromal regions in order to compute a tumour bulk mask. We then detect TILs within the tumour-associated stroma, generating a TILs score by closely mirroring the pathologist's workflow. Our method exhibits state-of-the-art performance in segmenting tumour/stroma areas and TILs detection, as demonstrated by internal cross-validation on the TiGER Challenge training dataset and evaluation on the final leaderboards. Additionally, our TILs score proves competitive in predicting survival outcomes within the same challenge, underscoring the clinical relevance and potential of our automated TILs scoring pipeline as a breast cancer prognostic tool.

Mark Eastwood, John Pocock, Mostafa Jahanifar et al.

Digital pathology has gained significant traction in modern healthcare systems. This shift from optical microscopes to digital imagery brings with it the potential for improved diagnosis, efficiency, and the integration of AI tools into the pathologists workflow. A critical aspect of this is visualization. Throughout the development of a machine learning (ML) model in digital pathology, it is crucial to have flexible, openly available tools to visualize models, from their outputs and predictions to the underlying annotations and images used to train or test a model. We introduce TIAViz, a Python-based visualization tool built into TIAToolbox which allows flexible, interactive, fully zoomable overlay of a wide variety of information onto whole slide images, including graphs, heatmaps, segmentations, annotations and other WSIs. The UI is browser-based, allowing use either locally, on a remote machine, or on a server to provide publicly available demos. This tool is open source and is made available at: https://github.com/TissueImageAnalytics/tiatoolbox and via pip installation (pip install tiatoolbox) and conda as part of TIAToolbox.

Behnaz Elhaminia, Abdullah Alsalemi, Esha Nasir et al.

Whole slide image (WSI) registration is an essential task for analysing the tumour microenvironment (TME) in histopathology. It involves the alignment of spatial information between WSIs of the same section or serial sections of a tissue sample. The tissue sections are usually stained with single or multiple biomarkers before imaging, and the goal is to identify neighbouring nuclei along the Z-axis for creating a 3D image or identifying subclasses of cells in the TME. This task is considerably more challenging compared to radiology image registration, such as magnetic resonance imaging or computed tomography, due to various factors. These include gigapixel size of images, variations in appearance between differently stained tissues, changes in structure and morphology between non-consecutive sections, and the presence of artefacts, tears, and deformations. Currently, there is a noticeable gap in the literature regarding a review of the current approaches and their limitations, as well as the challenges and opportunities they present. We aim to provide a comprehensive understanding of the available approaches and their application for various purposes. Furthermore, we investigate current deep learning methods used for WSI registration, emphasising their diverse methodologies. We examine the available datasets and explore tools and software employed in the field. Finally, we identify open challenges and potential future trends in this area of research.

Esha Sadia Nasir, Jiaqi Lv, Mostafa Jahanifar et al.

Automated detection and classification of mitotic figures especially distinguishing atypical from normal remain critical challenges in computational pathology. We present MitoDetect++, a unified deep learning pipeline designed for the MIDOG 2025 challenge, addressing both mitosis detection and atypical mitosis classification. For detection (Track 1), we employ a U-Net-based encoder-decoder architecture with EfficientNetV2-L as the backbone, enhanced with attention modules, and trained via combined segmentation losses. For classification (Track 2), we leverage the Virchow2 vision transformer, fine-tuned efficiently using Low-Rank Adaptation (LoRA) to minimize resource consumption. To improve generalization and mitigate domain shifts, we integrate strong augmentations, focal loss, and group-aware stratified 5-fold cross-validation. At inference, we deploy test-time augmentation (TTA) to boost robustness. Our method achieves a balanced accuracy of 0.892 across validation domains, highlighting its clinical applicability and scalability across tasks.

Simon Graham, Quoc Dang Vu, Mostafa Jahanifar et al.

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advances in deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper, we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumina and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable meaningful simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve the performance of additional tasks via transfer learning, including nuclear classification and signet ring cell detection. As part of this work, we train our developed Cerberus model on a huge amount of data, consisting of over 600K objects for segmentation and 440K patches for classification. We use our approach to process 599 colorectal whole-slide images from TCGA, where we localise 377 million, 900K and 2.1 million nuclei, glands and lumina, respectively and make the results available to the community for downstream analysis.

Simon Graham, Mostafa Jahanifar, Quoc Dang Vu et al.

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability. To help drive forward research and innovation for automatic nuclei recognition in CPath, we organise the Colon Nuclei Identification and Counting (CoNIC) Challenge. The challenge encourages researchers to develop algorithms that perform segmentation, classification and counting of nuclei within the current largest known publicly available nuclei-level dataset in CPath, containing around half a million labelled nuclei. Therefore, the CoNIC challenge utilises over 10 times the number of nuclei as the previous largest challenge dataset for nuclei recognition. It is important for algorithms to be robust to input variation if we wish to deploy them in a clinical setting. Therefore, as part of this challenge we will also test the sensitivity of each submitted algorithm to certain input variations.

Mostafa Jahanifar, Adam Shephard, Neda Zamani Tajeddin et al.

The detection of mitotic figures from different scanners/sites remains an important topic of research, owing to its potential in assisting clinicians with tumour grading. The MItosis DOmain Generalization (MIDOG) challenge aims to test the robustness of detection models on unseen data from multiple scanners for this task. We present a short summary of the approach employed by the TIA Centre team to address this challenge. Our approach is based on a hybrid detection model, where mitotic candidates are segmented on stain normalised images, before being refined by a deep learning classifier. Cross-validation on the training images achieved the F1-score of 0.786 and 0.765 on the preliminary test set, demonstrating the generalizability of our model to unseen data from new scanners.

Adam J. Shephard, Simon Graham, R. M. Saad Bashir et al.

Oral epithelial dysplasia (OED) is a pre-malignant histopathological diagnosis given to lesions of the oral cavity. Predicting OED grade or whether a case will transition to malignancy is critical for early detection and appropriate treatment. OED typically begins in the lower third of the epithelium before progressing upwards with grade severity, thus we have suggested that segmenting intra-epithelial layers, in addition to individual nuclei, may enable researchers to evaluate important layer-specific morphological features for grade/malignancy prediction. We present HoVer-Net+, a deep learning framework to simultaneously segment (and classify) nuclei and (intra-)epithelial layers in H&E stained slides from OED cases. The proposed architecture consists of an encoder branch and four decoder branches for simultaneous instance segmentation of nuclei and semantic segmentation of the epithelial layers. We show that the proposed model achieves the state-of-the-art (SOTA) performance in both tasks, with no additional costs when compared to previous SOTA methods for each task. To the best of our knowledge, ours is the first method for simultaneous nuclear instance segmentation and semantic tissue segmentation, with potential for use in computational pathology for other similar simultaneous tasks and for future studies into malignancy prediction.

Mostafa Jahanifar, Neda Zamani Tajeddin, Navid Alemi Koohbanani et al.

From the simple measurement of tissue attributes in pathology workflow to designing an explainable diagnostic/prognostic AI tool, access to accurate semantic segmentation of tissue regions in histology images is a prerequisite. However, delineating different tissue regions manually is a laborious, time-consuming and costly task that requires expert knowledge. On the other hand, the state-of-the-art automatic deep learning models for semantic segmentation require lots of annotated training data and there are only a limited number of tissue region annotated images publicly available. To obviate this issue in computational pathology projects and collect large-scale region annotations efficiently, we propose an efficient interactive segmentation network that requires minimum input from the user to accurately annotate different tissue types in the histology image. The user is only required to draw a simple squiggle inside each region of interest so it will be used as the guiding signal for the model. To deal with the complex appearance and amorph geometry of different tissue regions we introduce several automatic and minimalistic guiding signal generation techniques that help the model to become robust against the variation in the user input. By experimenting on a dataset of breast cancer images, we show that not only does our proposed method speed up the interactive annotation process, it can also outperform the existing automatic and interactive region segmentation models.

Simon Graham, Mostafa Jahanifar, Ayesha Azam et al.

The development of deep segmentation models for computational pathology (CPath) can help foster the investigation of interpretable morphological biomarkers. Yet, there is a major bottleneck in the success of such approaches because supervised deep learning models require an abundance of accurately labelled data. This issue is exacerbated in the field of CPath because the generation of detailed annotations usually demands the input of a pathologist to be able to distinguish between different tissue constructs and nuclei. Manually labelling nuclei may not be a feasible approach for collecting large-scale annotated datasets, especially when a single image region can contain thousands of different cells. However, solely relying on automatic generation of annotations will limit the accuracy and reliability of ground truth. Therefore, to help overcome the above challenges, we propose a multi-stage annotation pipeline to enable the collection of large-scale datasets for histology image analysis, with pathologist-in-the-loop refinement steps. Using this pipeline, we generate the largest known nuclear instance segmentation and classification dataset, containing nearly half a million labelled nuclei in H&E stained colon tissue. We have released the dataset and encourage the research community to utilise it to drive forward the development of downstream cell-based models in CPath.

Neda Zamanitajeddin, Mostafa Jahanifar, Nasir Rajpoot

Digitization of histology images and the advent of new computational methods, like deep learning, have helped the automatic grading of colorectal adenocarcinoma cancer (CRA). Present automated CRA grading methods, however, usually use tiny image patches and thus fail to integrate the entire tissue micro-architecture for grading purposes. To tackle these challenges, we propose to use a statistical network analysis method to describe the complex structure of the tissue micro-environment by modelling nuclei and their connections as a network. We show that by analyzing only the interactions between the cells in a network, we can extract highly discriminative statistical features for CRA grading. Unlike other deep learning or convolutional graph-based approaches, our method is highly scalable (can be used for cell networks consist of millions of nodes), completely explainable, and computationally inexpensive. We create cell networks on a broad CRC histology image dataset, experiment with our method, and report state-of-the-art performance for the prediction of three-class CRA grading.

Noorul Wahab, Islam M Miligy, Katherine Dodd et al.

Recent advances in whole slide imaging (WSI) technology have led to the development of a myriad of computer vision and artificial intelligence (AI) based diagnostic, prognostic, and predictive algorithms. Computational Pathology (CPath) offers an integrated solution to utilize information embedded in pathology WSIs beyond what we obtain through visual assessment. For automated analysis of WSIs and validation of machine learning (ML) models, annotations at the slide, tissue and cellular levels are required. The annotation of important visual constructs in pathology images is an important component of CPath projects. Improper annotations can result in algorithms which are hard to interpret and can potentially produce inaccurate and inconsistent results. Despite the crucial role of annotations in CPath projects, there are no well-defined guidelines or best practices on how annotations should be carried out. In this paper, we address this shortcoming by presenting the experience and best practices acquired during the execution of a large-scale annotation exercise involving a multidisciplinary team of pathologists, ML experts and researchers as part of the Pathology image data Lake for Analytics, Knowledge and Education (PathLAKE) consortium. We present a real-world case study along with examples of different types of annotations, diagnostic algorithm, annotation data dictionary and annotation constructs. The analyses reported in this work highlight best practice recommendations that can be used as annotation guidelines over the lifecycle of a CPath project.

Mostafa Jahanifar, Neda Zamani Tajeddin, Meisam Hasani et al.

Tendon injuries like tendinopathies, full and partial thickness tears are prevalent, and the supraspinatus tendon (SST) is the most vulnerable ones in the rotator cuff. Early diagnosis of SST tendinopathies is of high importance and hard to achieve using ultrasound imaging. In this paper, an automatic tendinopathy recognition framework based on convolutional neural networks has been proposed to assist the diagnosis. This framework has two essential parts of tendon segmentation and classification. Tendon segmentation is done through a novel network, NASUNet, which follows an encoder-decoder architecture paradigm and utilizes a multi-scale Enlarging cell. Moreover, a general classification pipeline has been proposed for tendinopathy recognition, which supports different base models as the feature extractor engine. Two feature maps comprising positional information of the tendon region have been introduced as the network input to make the classification network spatial-aware. To evaluate the tendinopathy recognition system, a data set consisting of 100 SST ultrasound images have been acquired, in which tendinopathy cases are double-verified by magnetic resonance imaging. In both segmentation and classification tasks, lack of training data has been compensated by incorporating knowledge transferring, transfer learning, and data augmentation techniques. In cross-validation experiments, the proposed tendinopathy recognition model achieves 91% accuracy, 86.67% sensitivity, and 92.86% specificity, showing state-of-the-art performance against other models.

Navid Alemi Koohbanani, Mostafa Jahanifar, Neda Zamani Tajadin et al.

Object segmentation is an important step in the workflow of computational pathology. Deep learning based models generally require large amount of labeled data for precise and reliable prediction. However, collecting labeled data is expensive because it often requires expert knowledge, particularly in medical imaging domain where labels are the result of a time-consuming analysis made by one or more human experts. As nuclei, cells and glands are fundamental objects for downstream analysis in computational pathology/cytology, in this paper we propose a simple CNN-based approach to speed up collecting annotations for these objects which requires minimum interaction from the annotator. We show that for nuclei and cells in histology and cytology images, one click inside each object is enough for NuClick to yield a precise annotation. For multicellular structures such as glands, we propose a novel approach to provide the NuClick with a squiggle as a guiding signal, enabling it to segment the glandular boundaries. These supervisory signals are fed to the network as auxiliary inputs along with RGB channels. With detailed experiments, we show that NuClick is adaptable to the object scale, robust against variations in the user input, adaptable to new domains, and delivers reliable annotations. An instance segmentation model trained on masks generated by NuClick achieved the first rank in LYON19 challenge. As exemplar outputs of our framework, we are releasing two datasets: 1) a dataset of lymphocyte annotations within IHC images, and 2) a dataset of segmented WBCs in blood smear images.

Jevgenij Gamper, Navid Alemi Koohbanani, Ksenija Benes et al.

The emerging area of computational pathology (CPath) is ripe ground for the application of deep learning (DL) methods to healthcare due to the sheer volume of raw pixel data in whole-slide images (WSIs) of cancerous tissue slides. However, it is imperative for the DL algorithms relying on nuclei-level details to be able to cope with data from `the clinical wild', which tends to be quite challenging. We study, and extend recently released PanNuke dataset consisting of ~200,000 nuclei categorized into 5 clinically important classes for the challenging tasks of segmenting and classifying nuclei in WSIs. Previous pan-cancer datasets consisted of only up to 9 different tissues and up to 21,000 unlabeled nuclei and just over 24,000 labeled nuclei with segmentation masks. PanNuke consists of 19 different tissue types that have been semi-automatically annotated and quality controlled by clinical pathologists, leading to a dataset with statistics similar to the clinical wild and with minimal selection bias. We study the performance of segmentation and classification models when applied to the proposed dataset and demonstrate the application of models trained on PanNuke to whole-slide images. We provide comprehensive statistics about the dataset and outline recommendations and research directions to address the limitations of existing DL tools when applied to real-world CPath applications.

Mostafa Jahanifar, Navid Alemi Koohbanani, Nasir Rajpoot

Best performing nuclear segmentation methods are based on deep learning algorithms that require a large amount of annotated data. However, collecting annotations for nuclear segmentation is a very labor-intensive and time-consuming task. Thereby, providing a tool that can facilitate and speed up this procedure is very demanding. Here we propose a simple yet efficient framework based on convolutional neural networks, named NuClick, which can precisely segment nuclei boundaries by accepting a single point position (or click) inside each nucleus. Based on the clicked positions, inclusion and exclusion maps are generated which comprise 2D Gaussian distributions centered on those positions. These maps serve as guiding signals for the network as they are concatenated to the input image. The inclusion map focuses on the desired nucleus while the exclusion map indicates neighboring nuclei and improve the results of segmentation in scenes with nuclei clutter. The NuClick not only facilitates collecting more annotation from unseen data but also leads to superior segmentation output for deep models. It is also worth mentioning that an instance segmentation model trained on NuClick generated labels was able to rank first in LYON19 challenge.

Navid Alemi Koohbanani, Mostafa Jahanifar, Ali Gooya et al.

Nuclear segmentation in histology images is a challenging task due to significant variations in the shape and appearance of nuclei. One of the main hurdles in nuclear instance segmentation is overlapping nuclei where a smart algorithm is needed to separate each nucleus. In this paper, we introduce a proposal-free deep learning based framework to address these challenges. To this end, we propose a spatially-aware network (SpaNet) to capture spatial information in a multi-scale manner. A dual-head variation of the SpaNet is first utilized to predict the pixel-wise segmentation and centroid detection maps of nuclei. Based on these outputs, a single-head SpaNet predicts the positional information related to each nucleus instance. Spectral clustering method is applied on the output of the last SpaNet, which utilizes the nuclear mask and the Gaussian-like detection map for determining the connected components and associated cluster identifiers, respectively. The output of the clustering method is the final nuclear instance segmentation mask. We applied our method on a publicly available multi-organ data set and achieved state-of-the-art performance for nuclear segmentation.

Mostafa Jahanifar, Neda Zamani Tajeddin, Navid Alemi Koohbanani et al.

Computer-aided diagnosis systems for classification of different type of skin lesions have been an active field of research in recent decades. It has been shown that introducing lesions and their attributes masks into lesion classification pipeline can greatly improve the performance. In this paper, we propose a framework by incorporating transfer learning for segmenting lesions and their attributes based on the convolutional neural networks. The proposed framework is based on the encoder-decoder architecture which utilizes a variety of pre-trained networks in the encoding path and generates the prediction map by combining multi-scale information in decoding path using a pyramid pooling manner. To address the lack of training data and increase the proposed model generalization, an extensive set of novel domain-specific augmentation routines have been applied to simulate the real variations in dermoscopy images. Finally, by performing broad experiments on three different data sets obtained from International Skin Imaging Collaboration archive (ISIC2016, ISIC2017, and ISIC2018 challenges data sets), we show that the proposed method outperforms other state-of-the-art approaches for ISIC2016 and ISIC2017 segmentation task and achieved the first rank on the leader-board of ISIC2018 attribute detection task.

Navid Alemi Koohababni, Mostafa Jahanifar, Ali Gooya et al.

Nuclei detection is an important task in the histology domain as it is a main step toward further analysis such as cell counting, cell segmentation, study of cell connections, etc. This is a challenging task due to the complex texture of histology image, variation in shape, and touching cells. To tackle these hurdles, many approaches have been proposed in the literature where deep learning methods stand on top in terms of performance. Hence, in this paper, we propose a novel framework for nuclei detection based on Mixture Density Networks (MDNs). These networks are suitable to map a single input to several possible outputs and we utilize this property to detect multiple seeds in a single image patch. A new modified form of a cost function is proposed for training and handling patches with missing nuclei. The probability maps of the nuclei in the individual patches are next combined to generate the final image-wide result. The experimental results show the state-of-the-art performance on complex colorectal adenocarcinoma dataset.

Mostafa Jahanifar, Neda Zamani Tajeddin, Babak Mohammadzadeh Asl et al.

Lesion segmentation is the first step in most automatic melanoma recognition systems. Deficiencies and difficulties in dermoscopic images such as color inconstancy, hair occlusion, dark corners and color charts make lesion segmentation an intricate task. In order to detect the lesion in the presence of these problems, we propose a supervised saliency detection method tailored for dermoscopic images based on the discriminative regional feature integration (DRFI). DRFI method incorporates multi-level segmentation, regional contrast, property, background descriptors, and a random forest regressor to create saliency scores for each region in the image. In our improved saliency detection method, mDRFI, we have added some new features to regional property descriptors. Also, in order to achieve more robust regional background descriptors, a thresholding algorithm is proposed to obtain a new pseudo-background region. Findings reveal that mDRFI is superior to DRFI in detecting the lesion as the salient object in dermoscopic images. The proposed overall lesion segmentation framework uses detected saliency map to construct an initial mask of the lesion through thresholding and post-processing operations. The initial mask is then evolving in a level set framework to fit better on the lesion's boundaries. The results of evaluation tests on three public datasets show that our proposed segmentation method outperforms the other conventional state-of-the-art segmentation algorithms and its performance is comparable with most recent approaches that are based on deep convolutional neural networks.