SUMMARY: Pulmonary Hypertension (PH) is a severe and life-threatening disease that increases mortality rates by 7-fold. Pulmonary Arterial Hypertension (PAH, WHO Group 1) is the most severe subtype, with a median survival of just three years. PAH must be distinguished from another subtype called Pulmonary Venous Hypertension (PVH, WHO Group 2) because PAH treatments can harm PVH patients. Unfortunately, the current diagnostic and prognostic process for PAH is slow, taking 2-4 years after symptom onset, and relies on a series of costly, inconclusive, noninvasive tests ending with invasive catheterization for conclusive diagnosis. Delays and invasive diagnostics worsen patient suffering and jeopardize the chances of early effective treatment. Thus, there is an urgent need for a streamlined, accurate non-invasive tool for PAH diagnosis, classification, and prognosis. Our project aims to develop a '4D Right-Heart Virtual Catheter (vCath)' capable of providing a comprehensive hemodynamic analysis of all right heart chambers in less than two minutes, utilizing a single 4D Flow MRI scan. Our 4D vCath technology combines advanced mathematical modeling and fluid dynamics with 4D Flow MRI to create a personalized digital catheter for streamlined, simultaneous analysis of multiple advanced hemodynamic parameters. With our innovative solution, patients can receive a full set of diagnostic and prognostic hemodynamic assessments of all right heart chambers from a single noninvasive MRI scan. Our technology enables the accurate diagnosis of PAH, differentiation of PAH from PVH, and precise assessment of PAH severity prognosis, eliminating the need for multiple costly tests, expediting early diagnosis, and enabling personalized severity monitoring. This approach has the potential to widen access to essential care for vulnerable PH patients who cannot undergo invasive CATH or multiple tests. Our multi-center project encompasses 3 specific Aims: Aim 1: Develop an automated and rapid 4D RH vCath for a comprehensive assessment of right heart hemodynamics and perform extensive inter-center and inter-vendor uncertainty quantification in healthy controls. Aim 2: Conduct a multi-center cross-sectional study involving 165 subjects from three sites (Northwestern, Mayo Clinic, and UT Southwestern), including PAH patients, PVH patients, and healthy controls. The study aims to differentiate between PAH and PVH subtypes and assess the correlation of 4D vCath metrics with invasive Cath and MRI measures of right heart dysfunction in PH patients. Aim 3: Conduct a multi-center longitudinal PAH outcome study, including a 1-year follow-up for PAH patients evaluating the prognostic significance of 4D vCath for personalized evaluation and monitoring of PAH severity. If successful, this project has the potential to revolutionize PH management by accelerating noninvasive diagnosis, personalizing prognosis, and increasing access to timely care for a broader spectrum of patients includin...