Simon Graham

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 .

Yiping Jiao, Jeroen van der Laak, Shadi Albarqouni et al. · eth-zurich

We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in histopathological images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform. LYSTO has supported a number of research in lymphocyte assessment in oncology. LYSTO will be a long-lasting educational challenge for deep learning and digital pathology, it is available at https://lysto.grand-challenge.org/.

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.

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 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.

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.

Yan Jia, Harriet Evans, Zoe Porter et al.

In this paper we propose an advanced approach to integrating artificial intelligence (AI) into healthcare: autonomous decision support. This approach allows the AI algorithm to act autonomously for a subset of patient cases whilst serving a supportive role in other subsets of patient cases based on defined delegation criteria. By leveraging the complementary strengths of both humans and AI, it aims to deliver greater overall performance than existing human-AI teaming models. It ensures safe handling of patient cases and potentially reduces clinician review time, whilst being mindful of AI tool limitations. After setting the approach within the context of current human-AI teaming models, we outline the delegation criteria and apply them to a specific AI-based tool used in histopathology. The potential impact of the approach and the regulatory requirements for its successful implementation are then discussed.

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.

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.

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.

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.

Srijay Deshpande, Fayyaz Minhas, Simon Graham et al.

Synthetic images can be used for the development and evaluation of deep learning algorithms in the context of limited availability of data. In the field of computational pathology, where histology images are large in size and visual context is crucial, synthesis of large high resolution images via generative modeling is a challenging task. This is due to memory and computational constraints hindering the generation of large images. To address this challenge, we propose a novel SAFRON (Stitching Across the FRONtiers) framework to construct realistic, large high resolution tissue image tiles from ground truth annotations while preserving morphological features and with minimal boundary artifacts. We show that the proposed method can generate realistic image tiles of arbitrarily large size after training it on relatively small image patches. We demonstrate that our model can generate high quality images, both visually and in terms of the Frechet Inception Distance. Compared to other existing approaches, our framework is efficient in terms of the memory requirements for training and also in terms of the number of computations to construct a large high-resolution image. We also show that training on synthetic data generated by SAFRON can significantly boost the performance of a state-of-the-art algorithm for gland segmentation in colorectal cancer histology images. Sample high resolution images generated using SAFRON are available at the URL: https://warwick.ac.uk/TIALab/SAFRON

Simon Graham, David Epstein, Nasir Rajpoot

Histology images are inherently symmetric under rotation, where each orientation is equally as likely to appear. However, this rotational symmetry is not widely utilised as prior knowledge in modern Convolutional Neural Networks (CNNs), resulting in data hungry models that learn independent features at each orientation. Allowing CNNs to be rotation-equivariant removes the necessity to learn this set of transformations from the data and instead frees up model capacity, allowing more discriminative features to be learned. This reduction in the number of required parameters also reduces the risk of overfitting. In this paper, we propose Dense Steerable Filter CNNs (DSF-CNNs) that use group convolutions with multiple rotated copies of each filter in a densely connected framework. Each filter is defined as a linear combination of steerable basis filters, enabling exact rotation and decreasing the number of trainable parameters compared to standard filters. We also provide the first in-depth comparison of different rotation-equivariant CNNs for histology image analysis and demonstrate the advantage of encoding rotational symmetry into modern architectures. We show that DSF-CNNs achieve state-of-the-art performance, with significantly fewer parameters, when applied to three different tasks in the area of computational pathology: breast tumour classification, colon gland segmentation and multi-tissue nuclear segmentation.

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.

Yanning Zhou, Simon Graham, Navid Alemi Koohbanani et al.

Colorectal cancer (CRC) grading is typically carried out by assessing the degree of gland formation within histology images. To do this, it is important to consider the overall tissue micro-environment by assessing the cell-level information along with the morphology of the gland. However, current automated methods for CRC grading typically utilise small image patches and therefore fail to incorporate the entire tissue micro-architecture for grading purposes. To overcome the challenges of CRC grading, we present a novel cell-graph convolutional neural network (CGC-Net) that converts each large histology image into a graph, where each node is represented by a nucleus within the original image and cellular interactions are denoted as edges between these nodes according to node similarity. The CGC-Net utilises nuclear appearance features in addition to the spatial location of nodes to further boost the performance of the algorithm. To enable nodes to fuse multi-scale information, we introduce Adaptive GraphSage, which is a graph convolution technique that combines multi-level features in a data-driven way. Furthermore, to deal with redundancy in the graph, we propose a sampling technique that removes nodes in areas of dense nuclear activity. We show that modeling the image as a graph enables us to effectively consider a much larger image (around 16$\times$ larger) than traditional patch-based approaches and model the complex structure of the tissue micro-environment. We construct cell graphs with an average of over 3,000 nodes on a large CRC histology image dataset and report state-of-the-art results as compared to recent patch-based as well as contextual patch-based techniques, demonstrating the effectiveness of our method.

Simon Graham, Quoc Dang Vu, Shan E Ahmed Raza et al.

Nuclear segmentation and classification within Haematoxylin & Eosin stained histology images is a fundamental prerequisite in the digital pathology work-flow. The development of automated methods for nuclear segmentation and classification enables the quantitative analysis of tens of thousands of nuclei within a whole-slide pathology image, opening up possibilities of further analysis of large-scale nuclear morphometry. However, automated nuclear segmentation and classification is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability such as the tumour cells. Additionally, some of the nuclei are often clustered together. To address these challenges, we present a novel convolutional neural network for simultaneous nuclear segmentation and classification that leverages the instance-rich information encoded within the vertical and horizontal distances of nuclear pixels to their centres of mass. These distances are then utilised to separate clustered nuclei, resulting in an accurate segmentation, particularly in areas with overlapping instances. Then for each segmented instance, the network predicts the type of nucleus via a devoted up-sampling branch. We demonstrate state-of-the-art performance compared to other methods on multiple independent multi-tissue histology image datasets. As part of this work, we introduce a new dataset of Haematoxylin & Eosin stained colorectal adenocarcinoma image tiles, containing 24,319 exhaustively annotated nuclei with associated class labels.

Quoc Dang Vu, Simon Graham, Minh Nguyen Nhat To et al.

High-resolution microscopy images of tissue specimens provide detailed information about the morphology of normal and diseased tissue. Image analysis of tissue morphology can help cancer researchers develop a better understanding of cancer biology. Segmentation of nuclei and classification of tissue images are two common tasks in tissue image analysis. Development of accurate and efficient algorithms for these tasks is a challenging problem because of the complexity of tissue morphology and tumor heterogeneity. In this paper we present two computer algorithms; one designed for segmentation of nuclei and the other for classification of whole slide tissue images. The segmentation algorithm implements a multiscale deep residual aggregation network to accurately segment nuclear material and then separate clumped nuclei into individual nuclei. The classification algorithm initially carries out patch-level classification via a deep learning method, then patch-level statistical and morphological features are used as input to a random forest regression model for whole slide image classification. The segmentation and classification algorithms were evaluated in the MICCAI 2017 Digital Pathology challenge. The segmentation algorithm achieved an accuracy score of 0.78. The classification algorithm achieved an accuracy score of 0.81.

Saad Ullah Akram, Talha Qaiser, Simon Graham et al.

Mitosis count is an important biomarker for prognosis of various cancers. At present, pathologists typically perform manual counting on a few selected regions of interest in breast whole-slide-images (WSIs) of patient biopsies. This task is very time-consuming, tedious and subjective. Automated mitosis detection methods have made great advances in recent years. However, these methods require exhaustive labeling of a large number of selected regions of interest. This task is very expensive because expert pathologists are needed for reliable and accurate annotations. In this paper, we present a semi-supervised mitosis detection method which is designed to leverage a large number of unlabeled breast cancer WSIs. As a result, our method capitalizes on the growing number of digitized histology images, without relying on exhaustive annotations, subsequently improving mitosis detection. Our method first learns a mitosis detector from labeled data, uses this detector to mine additional mitosis samples from unlabeled WSIs, and then trains the final model using this larger and diverse set of mitosis samples. The use of unlabeled data improves F1-score by $\sim$5\% compared to our best performing fully-supervised model on the TUPAC validation set. Our submission (single model) to TUPAC challenge ranks highly on the leaderboard with an F1-score of 0.64.

Mitko Veta, Yujing J. Heng, Nikolas Stathonikos et al.

Tumor proliferation is an important biomarker indicative of the prognosis of breast cancer patients. Assessment of tumor proliferation in a clinical setting is highly subjective and labor-intensive task. Previous efforts to automate tumor proliferation assessment by image analysis only focused on mitosis detection in predefined tumor regions. However, in a real-world scenario, automatic mitosis detection should be performed in whole-slide images (WSIs) and an automatic method should be able to produce a tumor proliferation score given a WSI as input. To address this, we organized the TUmor Proliferation Assessment Challenge 2016 (TUPAC16) on prediction of tumor proliferation scores from WSIs. The challenge dataset consisted of 500 training and 321 testing breast cancer histopathology WSIs. In order to ensure fair and independent evaluation, only the ground truth for the training dataset was provided to the challenge participants. The first task of the challenge was to predict mitotic scores, i.e., to reproduce the manual method of assessing tumor proliferation by a pathologist. The second task was to predict the gene expression based PAM50 proliferation scores from the WSI. The best performing automatic method for the first task achieved a quadratic-weighted Cohen's kappa score of $κ$ = 0.567, 95% CI [0.464, 0.671] between the predicted scores and the ground truth. For the second task, the predictions of the top method had a Spearman's correlation coefficient of r = 0.617, 95% CI [0.581 0.651] with the ground truth. This was the first study that investigated tumor proliferation assessment from WSIs. The achieved results are promising given the difficulty of the tasks and weakly-labelled nature of the ground truth. However, further research is needed to improve the practical utility of image analysis methods for this task.

Simon Graham, Hao Chen, Jevgenij Gamper et al.

The analysis of glandular morphology within colon histopathology images is an important step in determining the grade of colon cancer. Despite the importance of this task, manual segmentation is laborious, time-consuming and can suffer from subjectivity among pathologists. The rise of computational pathology has led to the development of automated methods for gland segmentation that aim to overcome the challenges of manual segmentation. However, this task is non-trivial due to the large variability in glandular appearance and the difficulty in differentiating between certain glandular and non-glandular histological structures. Furthermore, a measure of uncertainty is essential for diagnostic decision making. To address these challenges, we propose a fully convolutional neural network that counters the loss of information caused by max-pooling by re-introducing the original image at multiple points within the network. We also use atrous spatial pyramid pooling with varying dilation rates for preserving the resolution and multi-level aggregation. To incorporate uncertainty, we introduce random transformations during test time for an enhanced segmentation result that simultaneously generates an uncertainty map, highlighting areas of ambiguity. We show that this map can be used to define a metric for disregarding predictions with high uncertainty. The proposed network achieves state-of-the-art performance on the GlaS challenge dataset and on a second independent colorectal adenocarcinoma dataset. In addition, we perform gland instance segmentation on whole-slide images from two further datasets to highlight the generalisability of our method. As an extension, we introduce MILD-Net+ for simultaneous gland and lumen segmentation, to increase the diagnostic power of the network.

Shan E Ahmed Raza, Linda Cheung, Muhammad Shaban et al.

Object segmentation and structure localization are important steps in automated image analysis pipelines for microscopy images. We present a convolution neural network (CNN) based deep learning architecture for segmentation of objects in microscopy images. The proposed network can be used to segment cells, nuclei and glands in fluorescence microscopy and histology images after slight tuning of input parameters. The network trains at multiple resolutions of the input image, connects the intermediate layers for better localization and context and generates the output using multi-resolution deconvolution filters. The extra convolutional layers which bypass the max-pooling operation allow the network to train for variable input intensities and object size and make it robust to noisy data. We compare our results on publicly available data sets and show that the proposed network outperforms recent deep learning algorithms.