Faculty Publications
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Item Automated Molecular Subtyping of Breast Cancer Through Immunohistochemistry Image Analysis(Springer Science and Business Media Deutschland GmbH, 2023) Niyas, S.; Priya, S.; Oswal, R.; Mathew, T.; Kini, J.R.; Rajan, J.Molecular subtyping has a significant role in cancer prognosis and targeted therapy. However, the prevalent manual procedure for this has disadvantages, such as deficit of medical experts, inter-observer variability, and high time consumption. This paper suggests a novel approach to automate molecular subtyping of breast cancer using an end-to-end deep learning model. Immunohistochemistry (IHC) images of the tumor tissues are analyzed using a three-stage system to determine the subtype. A modified Res-UNet CNN architecture is used in the first stage to segregate the biomarker responses. This is followed by using a CNN classifier to determine the status of the four biomarkers. Finally, the biomarker statuses are combined to determine the specific subtype of breast cancer. For each IHC biomarker, the performance of segmentation models is analyzed qualitatively and quantitatively. In addition, the patient-level biomarker prediction results are also assessed. The findings of the suggested technique demonstrate the potential of computer-aided techniques to diagnose the subtypes of breast cancer. The proposed automated molecular subtyping approach can accelerate pathology procedures, considerably reduce pathologists’ workload, and minimize the overall cost and time required for diagnosis and treatment planning. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.Item A study about color normalization methods for histopathology images(Elsevier Ltd, 2018) Roy, S.; Kumar Jain, A.K.; Lal, S.; Kini, J.R.Histopathology images are used for the diagnosis of the cancerous disease by the examination of tissue with the help of Whole Slide Imaging (WSI) scanner. A decision support system works well by the analysis of the histopathology images but a lot of problems arise in its decision. Color variation in the histopathology images is occurring due to use of the different scanner, use of various equipments, different stain coloring and reactivity from a different manufacturer. In this paper, detailed study and performance evaluation of color normalization methods on histopathology image datasets are presented. Color normalization of the source image by transferring the mean color of the target image in the source image and also to separate stain present in the source image. Stain separation and color normalization of the histopathology images can be helped for both pathology and computerized decision support system. Quality performances of different color normalization methods are evaluated and compared in terms of quaternion structure similarity index matrix (QSSIM), structure similarity index matrix (SSIM) and Pearson correlation coefficient (PCC) on various histopathology image datasets. Our experimental analysis suggests that structure-preserving color normalization (SPCN) provides better qualitatively and qualitatively results in comparison to the all the presented methods for breast and colorectal cancer histopathology image datasets. © 2018 Elsevier LtdItem Computational methods for automated mitosis detection in histopathology images: A review(Elsevier Sp. z o.o., 2021) Mathew, T.; Kini, J.R.; Rajan, J.Mitosis detection is an important step in pathology procedures in the context of cancer diagnosis and prognosis. Prevalent process for this task is by manually observing Hematoxylin and Eosin (H & E) stained histopathology sections on glass slides through a microscope by trained pathologists. This conventional approach is tedious, error-prone, and has shown high inter-observer variability. With the advancement of computational technologies, automating mitosis detection by the use of image processing algorithms has attracted significant research interest. In the past decade, several methods appeared in the literature, addressing this problem and they have shown encouraging incremental progress towards a clinically usable solution. Mitosis count is an important parameter in grading of breast cancer and glioma, unlike other cancer types. Driven by the availability of multiple public datasets and open contests, most of the methods in literature address mitosis detection in breast cancer images. This paper is a comprehensive review of the methods published in the area of automated mitotic cell detection in H & E stained histopathology images of breast cancer in the last 10 years. We also discuss the current trends and future prospects of this clinically relevant task, augmenting humanity's fight against cancer. © 2020 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of SciencesItem Novel color normalization method for hematoxylin eosin stained histopathology images(Institute of Electrical and Electronics Engineers Inc., 2019) Roy, S.; Lal, S.; Kini, J.R.With the advent of computer-assisted diagnosis (CAD), the accuracy of cancer detection from histopathology images is significantly increased. However, color variation in the CAD system is inevitable due to the variability of stain concentration and manual tissue sectioning. The small variation in color may lead to the misclassification of cancer cells. Therefore, color normalization is a very much essential step prior to segmentation and classification in order to reduce the inter-variability of background color among a set of source images. In this paper, a novel color normalization method is proposed for Hematoxylin and Eosin stained histopathology images. Conventional Reinhard algorithm is modified in our proposed method by incorporating fuzzy logic. Moreover, mathematically, it is proved that our proposed method satisfies all three hypotheses of color normalization. Furthermore, several quality metrics are estimated locally for evaluating the performance of various color normalization methods. The experimental result reveals that our proposed method has outperformed all other benchmark methods. © 2019 IEEE.Item NucleiSegNet: Robust deep learning architecture for the nuclei segmentation of liver cancer histopathology images(Elsevier Ltd, 2021) Lal, S.; Das, D.; Alabhya, K.; Kanfade, A.; Kumar, A.; Kini, J.R.The nuclei segmentation of hematoxylin and eosin (H&E) stained histopathology images is an important prerequisite in designing a computer-aided diagnostics (CAD) system for cancer diagnosis and prognosis. Automated nuclei segmentation methods enable the qualitative and quantitative analysis of tens of thousands of nuclei within H&E stained histopathology images. However, a major challenge during nuclei segmentation is the segmentation of variable sized, touching nuclei. To address this challenge, we present NucleiSegNet - a robust deep learning network architecture for the nuclei segmentation of H&E stained liver cancer histopathology images. Our proposed architecture includes three blocks: a robust residual block, a bottleneck block, and an attention decoder block. The robust residual block is a newly proposed block for the efficient extraction of high-level semantic maps. The attention decoder block uses a new attention mechanism for efficient object localization, and it improves the proposed architecture's performance by reducing false positives. When applied to nuclei segmentation tasks, the proposed deep-learning architecture yielded superior results compared to state-of-the-art nuclei segmentation methods. We applied our proposed deep learning architecture for nuclei segmentation to a set of H&E stained histopathology images from two datasets, and our comprehensive results show that our proposed architecture outperforms state-of-the-art methods. As part of this work, we also introduced a new liver dataset (KMC liver dataset) of H&E stained liver cancer histopathology image tiles, containing 80 images with annotated nuclei procured from Kasturba Medical College (KMC), Mangalore, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India. The proposed model's source code is available at https://github.com/shyamfec/NucleiSegNet. © 2020 Elsevier LtdItem Automated Molecular Subtyping of Breast Carcinoma Using Deep Learning Techniques(Institute of Electrical and Electronics Engineers Inc., 2023) Niyas, S.; Bygari, R.; Naik, R.; Viswanath, B.; Ugwekar, D.; Mathew, T.; Kavya, J.; Kini, J.R.; Rajan, J.Objective: Molecular subtyping is an important procedure for prognosis and targeted therapy of breast carcinoma, the most common type of malignancy affecting women. Immunohistochemistry (IHC) analysis is the widely accepted method for molecular subtyping. It involves the assessment of the four molecular biomarkers namely estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and antigen Ki67 using appropriate antibody reagents. Conventionally, these biomarkers are assessed manually by a pathologist, who finally combines individual results to identify the molecular subtype. Molecular subtyping necessitates the status of all the four biomarkers together, and to the best of our knowledge, no such automated method exists. This paper proposes a novel deep learning framework for automatic molecular subtyping of breast cancer from IHC images. Methods and procedures: A modified LadderNet architecture is proposed to segment the immunopositive elements from ER, PR, HER2, and Ki67 biomarker slides. This architecture uses long skip connections to pass encoder feature space from different semantic levels to the decoder layers, allowing concurrent learning with multi-scale features. The entire architecture is an ensemble of multiple fully convolutional neural networks, and learning pathways are chosen adaptively based on input data. The segmentation stage is followed by a post-processing stage to quantify the extent of immunopositive elements to predict the final status for each biomarker. Results: The performance of segmentation models for each IHC biomarker is evaluated qualitatively and quantitatively. Furthermore, the biomarker prediction results are also evaluated. The results obtained by our method are highly in concordance with manual assessment by pathologists. Clinical impact: Accurate automated molecular subtyping can speed up this pathology procedure, reduce pathologists' workload and associated costs, and facilitate targeted treatment to obtain better outcomes. © 2013 IEEE.Item A deep learning based classifier framework for automated nuclear atypia scoring of breast carcinoma(Elsevier Ltd, 2023) Mathew, T.; Johnpaul, C.I.; Ajith, B.; Kini, J.R.; Rajan, J.Nuclear atypia scoring is an essential procedure in the grading of breast carcinoma. Manual procedure of nuclear atypia scoring is error-prone, and marked by pathologists’ disagreement and low reproducibility. Automated methods are actively attempted by researchers to solve the problems of manual scoring. In this work, we propose a novel deep learning-based framework for automated nuclear atypia scoring of breast cancer from histopathology slide images. The framework consists of three major phases namely preprocessing, deep learning, and postprocessing. The original three-class problem of atypia scoring at slide level is not suitable for direct application of deep learning algorithms. This is due to the large dimensions and structural complexity of slide images, compounded by the small sample size of the available dataset. Redesign of this problem into a six-class nuclei classification problem through a set of preprocessing steps to facilitate effective use of deep learning algorithms, and the flexibility of the proposed three-phase framework to use different algorithms in each phase are the novel aspects of the proposed work. We used the publicly available slide image dataset MITOS-ATYPIA that contains 600 slide images of high spatial dimension for the experiments. A five-fold cross validation with the train-test sample ratio 80:20 in each fold is used for the performance evaluation. The performance of the method based on this framework exceeds the state-of-the-art with the results 0.8766, 0.8760, and 0.8745 for the metrics precision, recall, and F1 score respectively. © 2023 Elsevier Ltd