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

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Abstract
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

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