David J Harrison

Georg Wölflein, In Hwa Um, David J Harrison et al.

The presence and density of specific types of immune cells are important to understand a patient's immune response to cancer. However, immunofluorescence staining required to identify T cell subtypes is expensive, time-consuming, and rarely performed in clinical settings. We present a framework to virtually stain Hoechst images (which are cheap and widespread) with both CD3 and CD8 to identify T cell subtypes in clear cell renal cell carcinoma using generative adversarial networks. Our proposed method jointly learns both staining tasks, incentivising the network to incorporate mutually beneficial information from each task. We devise a novel metric to quantify the virtual staining quality, and use it to evaluate our method.

Jessica Cooper, In Hwa Um, Ognjen Arandjelović et al.

Multiplex immunofluorescence and immunohistochemistry benefit patients by allowing cancer pathologists to identify several proteins expressed on the surface of cells, enabling cell classification, better understanding of the tumour micro-environment, more accurate diagnoses, prognoses, and tailored immunotherapy based on the immune status of individual patients. However, they are expensive and time consuming processes which require complex staining and imaging techniques by expert technicians. Hoechst staining is much cheaper and easier to perform, but is not typically used in this case as it binds to DNA rather than to the proteins targeted by immunofluorescent techniques, and it was not previously thought possible to differentiate cells expressing these proteins based only on DNA morphology. In this work we show otherwise, training a deep convolutional neural network to identify cells expressing three proteins (T lymphocyte markers CD3 and CD8, and the B lymphocyte marker CD20) with greater than 90% precision and recall, from Hoechst 33342 stained tissue only. Our model learns previously unknown morphological features associated with expression of these proteins which can be used to accurately differentiate lymphocyte subtypes for use in key prognostic metrics such as assessment of immune cell infiltration,and thereby predict and improve patient outcomes without the need for costly multiplex immunofluorescence.

Jessica Cooper, Ognjen Arandjelović, David J Harrison

Understanding the predictions made by Artificial Intelligence (AI) systems is becoming more and more important as deep learning models are used for increasingly complex and high-stakes tasks. Saliency mapping -- a popular visual attribution method -- is one important tool for this, but existing formulations are limited by either computational cost or architectural constraints. We therefore propose Hierarchical Perturbation, a very fast and completely model-agnostic method for interpreting model predictions with robust saliency maps. Using standard benchmarks and datasets, we show that our saliency maps are of competitive or superior quality to those generated by existing model-agnostic methods -- and are over 20 times faster to compute.