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.