4D-Flow MRI-Derived Wall Shear Stress as a Non-Invasive Biomarker for the Detection and Hemodynamic Characterization of Pulmonary Hypertension.

Invasive right heart catheterization (RHC) remains the reference standard for diagnosing pulmonary hypertension (PH), but there is a pressing need for non-invasive techniques to assess pulmonary hemodynamics. This study evaluates 4D-flow MRI-derived wall shear stress (WSS) for PH detection using the updated 2022 hemodynamic criteria, and the prediction of right ventriculo-pulmonary arterial (RV-PA) uncoupling to assess disease severity. 3D WSS was measured in the main (MPA), right (RPA), and left (LPA) pulmonary arteries in a retrospective validation cohort (41 PH patients, 23 non-PH) and then assessed in a prospective test cohort (23 PH patients, 17 healthy controls). For methodological validation, a patient-specific computational fluid dynamics (CFD) was performed in a subset of 16 patients from the validation cohort. RV-PA uncoupling was assessed on the cine MRI, using RV global longitudinal strain (GLS) < -15.3% and RVSV/RVESV < 1. Both 3D peak and time-averaged WSS were significantly reduced in PH patients compared with healthy controls. Global WSS metrics demonstrated the strongest correlations with invasive hemodynamic parameters, including mPAP (r = -0.75, p < 0.001) and PVR (r = -0.76, p < 0.001). ROC curve analysis identified a peak WSS cutoff of < 0.30 Pa (AUC 0.98) for PH detection, a threshold achieving 90% sensitivity and 100% specificity in the test cohort. Furthermore, a peak WSS threshold of < 0.18 Pa demonstrated excellent discriminative ability for RV-PA uncoupling. These findings support the potential integration of WSS analysis into routine CMR protocols as a non-invasive complement to RHC, showing promise for both diagnosis and a longitudinal biomarker for monitoring PH.