Poster Presentation: Han Kahvecioglu

ABSTRACT

Organ-scale functional atlas of the lungs

Han A. Kahvecioglu, Gabrielle N. Grifno, Robert LeBourdais, Aman Shankardass, Hadi T. Nia

Objectives: The lung’s ability to coordinate gas exchange, immune defense, and mechanical ventilation depends on tightly coupled cellular and biomechanical processes at organ scale. However, current imaging methods cannot capture both dynamic ventilation mechanics and spatial immune architecture at organ scale: histology fixes tissue and eliminates motion, live imaging lacks depth, and no existing technique resolves whole-lung mechanical behavior alongside cellular organization. As a result, there is lack of knowledge on how lung mechanics shape immune function and how diseases and aging disrupt this coupling. Here, we introduce an integrated multiscale imaging pipeline that generates the first dynamic, alveolar-resolution atlas of the entire mouse lung.

Methods: Using Nia Lab’s crystal ribcage system, intact mouse lungs are mechanically ventilated under physiologic-like conditions, and micron-scale μCT imaging at varying pressure points captures an organ-scale strain map for the lungs. The same lungs are then fixed, cleared, and multiplex-stained to map key cell types such as endothelial, epithelial, and immune cells. Image registration is used to overlay the dynamic features on the static atlas to provide the functional atlas of the lungs, revealing how immune and stromal organization relate to regional mechanical strain. By extending this platform to disease models such as emphysema, fibrosis, and cancer, we provide a framework to explain how mechanical failure caused by pathology drives immune dysregulation and tissue remodeling at organ scale. In addition, by extending the platform to young and aged lungs we provide an understanding of how aging affects the interactions between cellular cues and mechanical properties in the lungs.

Results/Conclusion: This platform fills a critical gap between micro- and macro-imaging, enabling mechanobiology-guided insights that cannot be obtained with either histology or in-vivo imaging alone. Ultimately, this approach establishes a foundation for understanding, and eventually targeting, the mechanical-immune interactions in lung health, disease, and aging.