Lymphocyte detection for cancer analysis using a novel fusion block based channel boosted CNN.

Tumor-infiltrating lymphocytes, specialized immune cells, are considered an important biomarker in cancer analysis. Automated lymphocyte detection is challenging due to its heterogeneous morphology, variable distribution, and presence of artifacts. In this work, we propose a novel Boosted Channels Fusion-based CNN "BCF-Lym-Detector" for lymphocyte detection in multiple cancer histology images. The proposed network initially selects candidate lymphocytic regions at the tissue level and then detects lymphocytes at the cellular level. The proposed "BCF-Lym-Detector" generates diverse boosted channels by utilizing the feature learning capability of different CNN architectures. In this connection, a new adaptive fusion block is developed to combine and select the most relevant lymphocyte-specific features from the generated enriched feature space. Multi-level feature learning is used to retain lymphocytic spatial information and detect lymphocytes with variable appearances. The assessment of the proposed "BCF-Lym-Detector" show substantial improvement in terms of F-score (0.93 and 0.84 on LYSTO and NuClick, respectively), which suggests that the diverse feature extraction and dynamic feature selection enhanced the feature learning capacity of the proposed network. Moreover, the proposed technique's generalization on unseen test sets with a good recall (0.75) and F-score (0.73) shows its potential use for pathologists' assistance.

Attention-guided multi-scale deep object detection framework for lymphocyte analysis in IHC histological images.

Tumor-infiltrating lymphocytes are specialized lymphocytes that can detect and kill cancerous cells. Their detection poses many challenges due to significant morphological variations, overlapping occurrence, artifact regions and high-class resemblance between clustered areas and artifacts. In this regard, a Lymphocyte Analysis Framework based on Deep Convolutional neural network (DC-Lym-AF) is proposed to analyze lymphocytes in immunohistochemistry images. The proposed framework comprises (i) pre-processing, (ii) screening phase, (iii) localization phase and (iv) post-processing. In the screening phase, a custom convolutional neural network architecture (lymphocyte dilated network) is developed to screen lymphocytic regions by performing a patch-level classification. This proposed architecture uses dilated convolutions and shortcut connections to capture multi-level variations and ensure reference-based learning. In contrast, the localization phase utilizes an attention-guided multi-scale lymphocyte detector to detect lymphocytes. The proposed detector extracts refined and multi-scale features by exploiting dilated convolutions, attention mechanism and feature pyramid network (FPN) using its custom attention-aware backbone. The proposed DC-Lym-AF shows exemplary performance on the NuClick dataset compared with the existing detection models, with an F-score and precision of 0.84 and 0.83, respectively. We verified the generalizability of our proposed framework by participating in a publically open LYON'19 challenge. Results in terms of detection rate (0.76) and F-score (0.73) suggest that the proposed DC-Lym-AF can effectively detect lymphocytes in immunohistochemistry-stained images collected from different laboratories. In addition, its promising generalization on several datasets implies that it can be turned into a medical diagnostic tool to investigate various histopathological problems. Graphical Abstract.

Detection of tumour infiltrating lymphocytes in CD3 and CD8 stained histopathological images using a two-phase deep CNN.

BACKGROUND: Immuno-score, a prognostic measure for cancer, employed in determining tumor grade and type, is generated by counting the number of Tumour-Infiltrating Lymphocytes (TILs) in CD3 and CD8 stained histopathological tissue samples. Significant stain variations and heterogeneity in lymphocytes' spatial distribution and density make automated counting of TILs' a challenging task. METHODS: This work addresses the aforementioned challenges by developing a pipeline "Two-Phase Deep Convolutional Neural Network based Lymphocyte Counter (TDC-LC)" to detect lymphocytes in CD3 and CD8 stained histology images. The proposed pipeline sequentially works by removing hard negative examples (artifacts) in the first phase using a custom CNN "LSATM-Net" that exploits the idea of a split, asymmetric transform, and merge. Whereas, in the second phase, instance segmentation is performed to detect and generate a lymphocyte count against the remaining samples. Furthermore, the effectiveness of the proposed pipeline is measured by comparing it with the state-of-the-art single- and two-stage detectors. The inference code is available at GitHub Repository https://github.com/m-mohsin-zafar/tdc-lc. RESULTS: The empirical evaluation on samples from LYSTO dataset shows that the proposed LSTAM-Net can learn variations in the images and precisely remove the hard negative stain artifacts with an F-score of 0.74. The detection analysis shows that the proposed TDC-LC outperforms the existing models in identifying and counting lymphocytes with high Recall (0.87) and F-score (0.89). Moreover, the commendable performance of the proposed TDC-LC in different organs suggests a good generalization. CONCLUSION: The promising performance of the proposed pipeline suggests that it can serve as an automated system for detecting and counting lymphocytes from patches of tissue samples thereby reducing the burden on pathologists.