Phagocytosis Unveiled: A Scalable and Interpretable Deep learning Framework for Neurodegenerative Disease Analysis

Quantifying the phagocytosis of dynamic, unstained cells is essential for evaluating neurodegenerative diseases. However, measuring rapid cell interactions and distinguishing cells from backgrounds make this task challenging when processing time-lapse phase-contrast video microscopy. In this study, we introduce a fully automated, scalable, and versatile realtime framework for quantifying and analyzing phagocytic activity. Our proposed pipeline can process large data-sets and includes a data quality verification module to counteract potential perturbations such as microscope movements and frame blurring. We also propose an explainable cell segmentation module to improve the interpretability of deep learning methods compared to black-box algorithms. This includes two interpretable deep learning capabilities: visual explanation and model simplification. We demonstrate that interpretability in deep learning is not the opposite of high performance, but rather provides essential deep learning algorithm optimization insights and solutions. Incorporating interpretable modules results in an efficient architecture design and optimized execution time. We apply this pipeline to quantify and analyze microglial cell phagocytosis in frontotemporal dementia (FTD) and obtain statistically reliable results showing that FTD mutant cells are larger and more aggressive than control cells. To stimulate translational approaches and future research, we release an open-source pipeline and a unique microglial cells phagocytosis dataset for immune system characterization in neurodegenerative diseases research. This pipeline and dataset will consistently crystallize future advances in this field, promoting the development of efficient and effective interpretable algorithms dedicated to this critical domain. https://github.com/ounissimehdi/PhagoStat