Faculty Publications

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A novel deep classifier framework for automated molecular subtyping of breast carcinoma using immunohistochemistry image analysis
(Elsevier Ltd, 2022) Mathew, T.; Niyas, S.; Johnpaul, C.I.; Kini, J.; Rajan, J.
Breast carcinoma has various subtypes based on the genetic factors involved in the pathogenesis of the malignancy. Identifying the exact subtype and providing targeted treatment to the patient can improve the survival chances. Molecular subtyping through immunohistochemistry analysis is a pathology procedure to determine the subtype of breast cancer. The existing manual procedure is tedious and involves assessing the status of the four vital molecular biomarkers present in the tumor tissues. In this paper, a deep learning-based framework for automated molecular subtyping of breast cancer is proposed. Digital slide images of the four biomarkers are separately processed by the proposed framework. In the preprocessing stage, the non-informative background regions from the images are separated. The patches extracted from the foreground regions are classified into target classes using convolutional neural network models trained for this purpose. Classification results are post-processed to predict the status of all the four biomarkers. The predictions for the individual biomarkers are finally consolidated as per clinical guidelines to determine the subtype of the cancer. The proposed system is evaluated for the performance of individual biomarker status prediction and patient-level subtype classification.For patient-level evaluation of biomarkers ER, PR, K67, and HER2, the proposed method gives F1 Scores 1.00, 1.00, 0.90, and 0.94 respectively, whereas for molecular subtyping an F1 score of 0.89 is obtained. In both these aspects, the proposed framework has given significant results that show the effectiveness of our approach. © 2022 Elsevier Ltd
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.
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

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