Deep learning-based segmentation accurately captures histological features in cancer-free lymph nodes of breast cancer patients

Histological changes in the cancer-free lymph nodes (LNs) can add to the risk prediction of developing distant metastasis for LN-positive breast cancer patients. We have previously shown that the formation of germinal centres and enlarged sinus are premetastatic features and indicative of superior prognosis. As Whole Slide Images (WSI) demonstrated suitability for detection of LN metastasis with high accuracy based on Convolutional Neural Networks (CNN), we extended the CNN assessments to the detection and segmentation of these premetastatic features. Materials For 136 breast cancer patients, retrospectively collected from Guy’s Hospital, 1,422 Whole Slide Images (WSI) of axillary LNs (containing 1 to 3 LNs per WSI) and primary invasive tumours were 40x scanned by the Hamamatsu Nanozoomer. Two pathologists manually annotated germinal centres and sinuses in 111 of these images facilitating the ground-truth masks for a binary segmentation task using deep learning models. Results Each WSI was split into a series of overlapping patches along with corresponding ground-truth masks at 2.5x, 5x and 10x. Fully Convolutional Neural Networks (FCNs) based on the U-Net architecture were trained on patches from 95 annotated WSI to perform a segmentation for both germinal centres and sinus, with the remaining images used for validation (n= 6) and test sets (n= 10). In addition to a vanilla U-Net encoder-decoder architecture, a model with an attention mechanism to filter feature maps along skip connections was also explored. Additionally, a U-Net with dilated convolutions at each convolution block was used in a multi-scale mechanism that combines features from three different resolutions. To increase the robustness of the FCNs, training data was augmented using random image rotation and different colour perturbation transformations. Predictions were made on regions of WSIs containing whole LNs and were compared with the pathologist annotations on holdout testing images. The Dice coefficient was used to compare the predicted segmentations with the ground-truth annotations. Standard U-Net and attention U-Net architectures achieved an average Dice coefficient of 0.75 across the holdout testing images at 2.5x magnification for germinal centres, with individual images achieving a Dice score above 0.8. Multiscale models achieved the best results at 10x magnification with an average Dice score of 0.85 for germinal centres and 0.75 for sinus. The trained models were then applied to > 1,300 unseen and non-annotated WSIs of axillary LNs. Conclusion Our developed FCN models allow an automated, precise, reproducible and time-efficient approach to annotate germinal centres and sinuses in cancer-free and metastatic LNs. Trained models are currently applied to >1,300 unseen and non-annotated WSIs of axillary LNs, and will demonstrate their comparable performance with manual pathological assessment.

Citation

’ Gregory Verghese, Anita Grigoriadis, Amit Sethi, Amit Lohan, Nikhil Cherian, Swati Meena, Harry Chinque, Fangfang Liu, Ed Martin, Tristan Clark, Cheryl Gillet, Julie Owen, Swapnil Rane. Deep learning-based segmentation accurately captures histological features in cancer-free lymph nodes of breast cancer patients [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-014.’