DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF) is a progressive, ultimately fatal form of idiopathic interstitial pneumonitis (IIP), with a 3 year survival rate of 0%. Diagnostic certainty of IPF is critical to patient management and therapeutic decision-making. Two new FDA-approved therapies, pirfenidone and nintedanib, have been shown to slow disease progression in IPF and brought new hope to IPF patients. Due to their high costs, side effects, and documented efficacy only in IPF, pulmonologists only prescribe these drugs to patients with a well- established diagnosis of IPF. Definitive IPF diagnosis can be made by chest CT alone in about half of cases when classic imaging features are present, which must include peripheral honeycombing. When CT does not visualize honeycombing, patients must undergo surgery to resect lung tissue and look for honeycombing microscopically to establish diagnostic certainty of IPF. Unfortunately, surgical lung resection has high risks of associated morbidity and mortality, including provoking further disease progression, and even death. There is a clear clinical need for a low risk method of microscopic IPF diagnosis. In this proposal, we take a hypothesis driven approach to determine whether bronchoscopic optical imaging can serve as a novel, low-risk, non- surgical paradigm for IPF diagnosis without surgery or tissue removal. Optical coherence tomography (OCT) provides rapid 3D visualization of large tissue volumes with microscopic resolutions (< 10 µm, comparable with low-power microscopy) well beyond the capabilities of CT. We have developed ultrathin bronchoscopic OCT catheters and conducted in vivo peripheral lung imaging in patients. We have shown in preliminary studies that endobronchial OCT can detect microscopic honeycombing (< 1 mm diameter) in IPF that is not visible with CT. We hypothesize that minimally invasive bronchoscopic OCT can detect microscopic honeycombing and diagnose IPF with high sensitivity and specificity. In Aim 1, we will develop and validate OCT diagnostic criteria to detect microscopic honeycombing and diagnose IPF. We will create a library of airway- based OCT with matched histology from ex vivo lung specimens from patients with suspected IIP. In Aim 2, we will conduct a pilot clinical study to test the translation of bronchoscopic OCT to identify microscopic honeycombing and diagnose IPF in vivo. If successful, these studies will result in the clinical translation of bronchoscopic OCT imaging as a minimally-invasive method for IPF diagnosis, mitigating the need for surgical diagnostic procedures. This proposal addresses a significant clinical problem in a way not previously achievable, and could lead to major innovations in IPF clinical management and therapeutic decision-making. CANDIDATE Dr. Hariri is an Instructor in Pathology on the tenure track at Harvard Medical School. Her long-term career goal is to become an independent physician-scientist us...