Pulmonary arterial hypertension (PAH) is a relatively poorly understood disease in children and requires constant monitoring and chronic treatment to mitigate excess right ventricular afterload effects. Such monitoring requires regular and frequently invasive clinical imaging sessions. However, even with invasive techniques, the extent of clinical information currently obtained is incomplete, involving primarily pulmonary vascular resistance (PVR) and its component parameters: mean pulmonary artery (PA) pressure and right sided cardiac output (Qp). Given this paucity of quantitative information currently available to evaluate PAH clinically, opportunities exist to develop and evaluate more comprehensive measures of PAH using a combination of advanced cardiovascular imaging and sophisticated computational modeling. Furthermore, information gained from such endeavors should also assist in the development of novel non-invasive diagnostics, which by allowing easier acquisition of pulmonary vascular characteristics, serial monitoring, and bedside evaluation of reactivity, should widen the clinician's ability to characterize this complex disease. The overall hypothesis for these studies is that pulmonary vascular input impedance provides a more comprehensive measure of pulmonary vascular function than PVR alone since impedance includes both dynamic (stiffness or compliance) and steady-state (resistance) components of the vascular circuit.
The aims of this project are therefore divided into studies establishing the use of impedance clinically, studies exploring why impedance is a good reflector of pulmonary vascular hemodynamics and mechanics, and studies developing novel non-invasive diagnostics that extract the relevant parameters found in invasivelymeasured impedance, namely PVR and pulmonary vascular stiffness (PVS). This K24 project proposes a unique combination of research studies and training efforts to advance clinical evaluation of PAH while training clinical research fellows with both solid fundamental understanding of underlying physics and hemodynamics and accurate application of such principles to novel clinical diagnostics.
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