Fluoroformer: Scaling multiple instance learning to multiplexed images via attention-based channel fusion

Abstract: Though multiple instance learning (MIL) has been a foundational strategy in computational pathology for processing whole slide images (WSIs), current approaches are designed for traditional hematoxylin and eosin (H&E) slides rather than emerging multiplexed technologies. Here, we present an MIL strategy, the Fluoroformer module, that is specifically tailored to multiplexed WSIs by leveraging scaled dot-product attention (SDPA) to interpretably fuse information across disparate channels. On a cohort of 434 non-small cell lung cancer (NSCLC) samples, we show that the Fluoroformer both obtains strong prognostic performance and recapitulates immuno-oncological hallmarks of NSCLC. Our technique thereby provides a path for adapting state-of-the-art AI techniques to emerging spatial biology assays.