By John Bakum
Breathing is something we do all the time without really thinking about too often. Unless you are outside on a poor air quality day and coughing because of pollution, or your house is too dusty, or even worse, if your lungs have been attacked by a pathogen or cancer.
At that point, you really start to think about what else besides oxygen you are inhaling and maybe what is the most effective way to deliver airborne allergy medications or vaccines. Where do those tiny particles go once they enter your lungs?
Turns out the answer to that question is vital for mitigating the potential harmful effects of pollution and pathogens and maximizing the positive effects of medicine and nasal-delivered vaccines.
Tracking these particles is incredibly challenging because they are so small. Imaging models like CT scans or MRIs lack the spatial and temporal specificity to track individual particles.
“We need to know both where these particles are going within the lungs,” said Associate Professor Hadi Nia (BME, MSE), “and when they get there.”
A new technology
Enter the crystal ribcage technology. Developed by Nia’s group, the Crystal Ribcage acts as a clear, protective shield for an animal’s lungs, allowing scientists to get a close view of how the lungs work in real-time and at a cellular level. What makes this technology special is that it doesn’t disrupt the lung’s natural processes — breathing and blood circulation continue as usual while the researchers observe.
In a paper published in Nature Biomedical Engineering, “Real time single particle imaging of functional lungs reveals mosaic-like patterns of aerosol deposition in alveoli,” Gabrielle Grifno, a doctoral student in Nia Lab, used the Crystal Ribcage to identify previously unrecognized details in the lung at the level of individual alveoli (air sacs).
“The crystal ribcage technology was essential to this discovery, as it enabled single-particle imaging of the intact, functioning lung in real-time at a scale not previously possible,” said Nia.
A pattern uncovered
This capability led to the discovery of a striking mosaic pattern in the lung. It was found that certain alveoli, termed “tiles,” consistently receive inhaled aerosols and airborne particles, whereas neighboring alveoli, termed “bands,” receive little to no deposition. Together, these tile and band regions form a highly organized mosaic-like pattern of particle exposure across the alveolar landscape.. This finding is crucial as it shows that these details influence how the lung is exposed to inhaled particles, including pollutants, allergens, pathogens, and therapeutics.
Grifno also discovered that the exposure patterns (which and when specific parts of the lung are exposed) are deterministic rather than random, meaning that the same alveoli are repeatedly exposed over a lifetime while others are relatively spared. This has important implications for lung health and disease, particularly during the earliest stages of disease progression. In conditions such as pneumonia and cancer, localized differences in exposure may shape where pathological processes emerge, how they evolve, and how they respond to therapy.
Motivated by this discovery, Nia and his team are probing both the origins and consequences of this discovery. To uncover the mechanisms that give rise to these patterns, they are leveraging advanced computational modeling of lung structure and transport and in parallel, employing state-of-the-art molecular biology and immunology approaches to determine how this pattern influences immune responses, tissue remodeling, and disease progression.
This research was done in collaboration with fellow ENG faculty Professor Béla Suki (BME, MSE) and Assistant Professor Liang Hao (BME) along with colleagues at the Chobanian & Avedisian School of Medicine: Professor Joseph Mizgerd, Associate Professor Giovanni Ligresti, and Research Assistant Professor Ahmed Raslan.