Clinical CT Imaging for Screening and Subtyping of Pulmonary Hypertension in COPD

COPD remains one of the leading causes of morbidity and mortality in the western hemisphere. Pulmonary hypertension (PH) remains one of the key complications of smoking related lung disease, the presence of which leads to increased morbidity and mortality. Treatments for pulmonary arterial hypertension (PAH; Group 1 PH) have led to significant improvements in life expectancy and quality of life but have not had success in PH associated with COPD. We believe that part of the reason for this is that pulmonary hypertension in COPD arises from a complex set of mechanisms with only a partial pathophysiologic overlap with PAH. Additionally, patients with COPD are at significant risk for postcapillary pulmonary hypertension due to elevated left-sided pressures, which complicate treatment with pulmonary vasodilators used in PAH. CT imaging is increasingly obtained in smokers and is now often part of a lung-cancer screening of smokers. Features of pulmonary vascular remodeling have been previously described in pulmonary hypertension. In this proposal we seek to better understand the changes in the pulmonary vasculature and their relationship to changes in the lung parenchyma using a comprehensive, advance set of features from CT imaging in patients with group 1 (PAH) and those with COPD. To accomplish this, we use PVDOMICS cohort, a NIH funded multicenter dataset of patients with pulmonary hypertension, the MGB cohort, a dataset spanning the Massachusetts General Hospital/Brigham and Women’s Hospital and affiliated hospitals (MGB) and COPDGene, a data set of 10,000+ smokers. We additionally another NIH funded cohort, CARDIA, which is a longitudinal study in a general population to establish normative values in the overall population. All these data sets have already collected accompanying CT scans. In the first Aim we use data with accurate hemodynamic diagnosis of PH to find CT features that predict the presence of PH. In the second Aim, we find CT features that are predictive of significant precapillary remodeling and that are shared with group 1 PH, for which treatments targeting precapillary PH work well. In Aim 3, we use the baseline and follow-up CT scans from COPDGene, to study how these CT markers evolve over time in relationship to the patient’s health. This study leverages data from PVDOMICS, COPDGene and CARDIA, three highly curated NIH funded datasets, as well as clinical data from two large hospitals with advanced lung programs. The study team has 15+ years of experience in analyzing CT imaging of the lung incorporated into the Chest Imaging Platform, an NIH funded software package. The PI has developed specific expertise in both COPD and pulmonary hypertension which is his main clinical focus. The completion of this study will lead to insights in using CT scans for the noninvasive diagnosis and screening of pulmonary hypertension in nonsmokers and smokers, as well as a better understanding of the mechanism and clinical impact of PH in smokers. Project Number: 1R01HL176686-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Farbod Rahaghi | Institution: BRIGHAM AND WOMEN'S HOSPITAL, BOSTON, MA | Award Amount: $812,189 | Activity Code: R01 | Study Section: Clinical Translational Imaging Science Study Section[CTIS] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL17668601