PathoGraph: An Attention-Based Graph Neural Network Capable of Prognostication Based on CD276 Labelling of Malignant Glioma Cells.

Computerized methods have been developed that allow quantitative morphological analyses of whole slide images (WSIs), e.g., of immunohistochemical stains. The latter are attractive because they can provide high-resolution data on the distribution of proteins in tissue. However, many immunohistochemical results are complex because the protein of interest occurs in multiple locations (in different cells and also extracellularly). We have recently established an artificial intelligence framework, PathoFusion which utilises a bifocal convolutional neural network (BCNN) model for detecting and counting arbitrarily definable morphological structures. We have now complemented this model by adding an attention-based graph neural network (abGCN) for the advanced analysis and automated interpretation of such data. Classical convolutional neural network (CNN) models suffer from limitations when handling global information. In contrast, our abGCN is capable of creating a graph representation of cellular detail from entire WSIs. This abGCN method combines attention learning with visualisation techniques that pinpoint the location of informative cells and highlight cell-cell interactions. We have analysed cellular labelling for CD276, a protein of great interest in cancer immunology and a potential marker of malignant glioma cells/putative glioma stem cells (GSCs). We are especially interested in the relationship between CD276 expression and prognosis. The graphs permit predicting individual patient survival on the basis of GSC community features. Our experiments lay a foundation for the use of the BCNN-abGCN tool chain in automated diagnostic prognostication using immunohistochemically labelled histological slides, but the method is essentially generic and potentially a widely usable tool in medical research and AI based healthcare applications.

Artificial intelligence techniques for neuropathological diagnostics and research.

Artificial intelligence (AI) research began in theoretical neurophysiology, and the resulting classical paper on the McCulloch-Pitts mathematical neuron was written in a psychiatry department almost 80 years ago. However, the application of AI in digital neuropathology is still in its infancy. Rapid progress is now being made, which prompted this article. Human brain diseases represent distinct system states that fall outside the normal spectrum. Many differ not only in functional but also in structural terms, and the morphology of abnormal nervous tissue forms the traditional basis of neuropathological disease classifications. However, only a few countries have the medical specialty of neuropathology, and, given the sheer number of newly developed histological tools that can be applied to the study of brain diseases, a tremendous shortage of qualified hands and eyes at the microscope is obvious. Similarly, in neuroanatomy, human observers no longer have the capacity to process the vast amounts of connectomics data. Therefore, it is reasonable to assume that advances in AI technology and, especially, whole-slide image (WSI) analysis will greatly aid neuropathological practice. In this paper, we discuss machine learning (ML) techniques that are important for understanding WSI analysis, such as traditional ML and deep learning, introduce a recently developed neuropathological AI termed PathoFusion, and present thoughts on some of the challenges that must be overcome before the full potential of AI in digital neuropathology can be realized.

An Open-Source AI Framework for the Analysis of Single Cells in Whole-Slide Images with a Note on CD276 in Glioblastoma.

Routine examination of entire histological slides at cellular resolution poses a significant if not insurmountable challenge to human observers. However, high-resolution data such as the cellular distribution of proteins in tissues, e.g., those obtained following immunochemical staining, are highly desirable. Our present study extends the applicability of the PathoFusion framework to the cellular level. We illustrate our approach using the detection of CD276 immunoreactive cells in glioblastoma as an example. Following automatic identification by means of PathoFusion's bifocal convolutional neural network (BCNN) model, individual cells are automatically profiled and counted. Only discriminable cells selected through data filtering and thresholding were segmented for cell-level analysis. Subsequently, we converted the detection signals into the corresponding heatmaps visualizing the distribution of the detected cells in entire whole-slide images of adjacent H&E-stained sections using the Discrete Wavelet Transform (DWT). Our results demonstrate that PathoFusion is capable of autonomously detecting and counting individual immunochemically labelled cells with a high prediction performance of 0.992 AUC and 97.7% accuracy. The data can be used for whole-slide cross-modality analyses, e.g., relationships between immunochemical signals and anaplastic histological features. PathoFusion has the potential to be applied to additional problems that seek to correlate heterogeneous data streams and to serve as a clinically applicable, weakly supervised system for histological image analyses in (neuro)pathology.