Transbronchial diagnosis and characterization of pulmonary hypertension with Mechanomicroscopy - Project Summary Pulmonary hypertension (PH) due to lung disease (Group 3) is one of the most prevalent and most lethal classifi- cations of PH. Two critical issues impede the effective clinical care of this disease: 1) prolonged time to diagnosis, due in part to the challenge of identifying the symptoms of the disease separate from those of the primary lung disease; and 2) complications in treatment due to the presence of multiple etiologies and the corresponding absence of a one-size-fits-all solution. Bronchoscopy is a commonly-employed procedure in the diagnosis, moni- toring, and treatment of the lung diseases of this group, and with the right tools would offer the perfect opportunity to simultaneously investigate the presence and development of PH as well. Our long-term goal is to provide a clinically viable endoscopic imaging platform for the early detection and enhanced personalized treatment of PH in patients undergoing bronchoscopy. This platform, Mechanomicroscopy, has the potential to assess pulmonary arterial pressure and remodeling quickly and with minimal clinical friction during the bronchoscopic procedure, resulting in 1) a significantly shortened path to diagnosis that doesn’t rely on the development of symptoms; and 2) direct structural assessments of pulmonary arteries that are suspected to be relevant to determining effective treatment. The objective of this proposal is to develop and validate Mechanomicroscopy for the transbronchial assessment of pulmonary artery pressure and arterial smooth muscle thickening, and to perform these assess- ments across a diverse population of individuals with Group 3 PH. In Aim 1 we will implement technological developments for our system that will allow us to identify pulmonary arteries in real-time, which will aid in the clinical efficiency of our imaging. In Aim 2 we will evaluate our diagnostic imaging criteria in an animal model, comparing and correlating our measurements of pulmonary artery pressure and pulmonary arterial smooth mus- cle thickness with those of the gold standards of right heart catheterization and histology. We will conduct a human study in Aim 3 in which we will image patients who have already undergone right heart catheterization and who do not have severe PH, again comparing our pressure measurements with right heart catheterization for human translation and analyzing arterial smooth muscle thicknesses across the diverse population to inform future studies focused on personalizing care.