Non-invasive Assessment of Pulmonary Vascular Function by MRI in Children with Pulmonary Arterial Hypertension Correlate with Invasive Measurements

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Project Summary Pulmonary arterial hypertension (PAH) is an incurable, progressive disease that affects both adults and children. While many pathophysiologic similarities exist between adult and pediatric pulmonary hypertension, the number of life years lost in children is much greater given limited long-term survival. Pediatric PAH is distinct from adult disease in the fact that the initial insult occurs during a critical period of maturation and lung development. Hemodynamic abnormalities in the developing lung may impact treatment response and the natural history of the disease in ways that have not been shown; and can remain a strong contributing factor in disease progression. Despite significant unique factors in pediatric PAH, research of this group is lacking, forcing the use of adult-based guidelines and therapies. As a result, management of pediatric PAH includes using invasive right heart catheterization (RHC) for serial diagnostic/prognostic evaluation. Serial RHC is costly, exposes children to repeated anesthesia and excessive radiation, and importantly, children undergoing catheterization for PAH may have catastrophic events including cardiorespiratory arrest and death. Despite these challenges inherent to an invasive procedure, there is no alternative for evaluating therapeutic direction for pediatric patients. This is a significant factor for the lack of research and targeted therapies for this vulnerable population. Cardiac MRI is the single imaging modality that allows assessment of both the ventricle and the vasculature involved in PAH pathophysiology, without radiation exposure or anesthesia in older children. In adult studies, MRI is emerging as a technique for evaluating vascular function, including, recently, vorticity and helicity by 4-dimensional (4D) velocity- encoded MRI. MRI also has the ability to evaluate the pulmonary vascular structure with high spatial resolution and may demonstrate developmental vascular changes in PAH. Our overall hypothesis is that MRI will reflect pulmonary hemodynamic status in patients with PAH similar to conventional RHC. Our long-range goal is to show that non-invasive imaging modality can diagnose and serially monitor PAH children and possibly minimize the need for RHC. Furthermore, novel vascular imaging by 4D MRI, along with conventional MRI, in the proximal vasculature will quantify significant alterations in maturing vascular function in children with PAH. MRI may be a powerful in identifying targeted therapy unique for children.