Image-based modeling and analysis of hemodynamics in pulmonary hypertension

Pulmonary hypertension is a rare disease characterized by abnormally elevated pulmonary artery blood pressures ultimately leading to right ventricular hypertrophy, dysfunction, and failure. There are many types of pulmonary hypertension ranging from pulmonary arterial hypertension(PAH) originating from remodeling of the small distal PAs in pediatric patients triggered by a congenital heart defect, to chronic thromboembolic pulmonary hypertension (CTEPH) in adults caused by long-term obstructions in the PAs that can lead to remodeling and elevated PA pressures. Due to limitations in current technology to quantify blood flow in vivo and in the small PAs, the hemodynamics leading to the initiation of PAH are unknown and PA hemodynamics associated with recovering RV function in patients with CTEPH have not been carefully detailed following pulmonary endarterectomy (PEA) to remove PA obstructions. In my thesis, I utilized image-based modeling and analysis to quantify the hemodynamics leading to initiation of PAH in infants with congenital heart defects and to assess novel PA flow metrics describing the recovery of CTEPH patients following a PEA in relation to the right ventricular (RV) reverse remodeling. PAH can be caused by congenital heart defects, such as a ventricular septal defect (VSD) where a hole in the ventricular septal wall leads to left-to-right shunting of blood in the ventricles and increased PA blood flow. The abnormal hemodynamics from the shunt may play a role in driving the initiation of PAH via impairment of PA endothelial cell (PAEC) gene regulation. However, in vivo hemodynamics of the distal PAs, where remodeling occurs, has not been well quantified in VSD patients. Computational fluid dynamics (CFD) has been used to quantify patient-specific hemodynamics. However, preliminary studies were limited by insufficient characterization of PA morphometry with development and disease. To characterize PAH initiation in VSD patients, we simulated hemodynamics throughout the entire PA tree using an improved computational model informed by scaling laws we developed to describe changes in PA morphometry. Patients with CTEPH undergoing a PEA experience remarkable recoveries in PA pressures and RV function. 4D-Flow magnetic resonance imaging (4DMRI) of the PAs has provided comprehensive, non-invasive evaluation of patients with pulmonary hypertension. We developed a semi-automated 4DMRI analysis pipeline to evaluate novel PA hemodynamic metrics. PEA was associated with major changes in 4DMRI metrics of PA flow and stiffness. Longitudinal analysis revealed that PA helicity was closely associated with pulmonary remodeling and RV reverse remodeling following a PEA. By leveraging and improving non-invasive image-based modeling and analysis methods, we quantified the PA hemodynamics in an infant under VSD conditions leading to the initiation of PAH and in adult patients with CTEPH recovering from surgical treatment. This quantification of PA hemodynamics in the context of pulmonary hypertension has helped improve future simulations of blood flow in the PAs in multiple pulmonary diseases, informed experimental studies investigating the mechanisms of PAH initiation, and can be used to further evaluate RV remodeling and patient recovery after surgical treatment in CTEPH patients

Keywords: Bioengineering.
Advisor: Marsden Alison (Alison Leslie)
Feinstein Jeffrey A.
Rabinovitch Marlene