Assessing Response to Inhaled Prostacyclin With Hyperpolarized Xe MRI

Overview

This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI techniques for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated too test gas exchange dynamics with high temporal resolution. The conventional 1H MRi scans will include a free-breathing ultra-short echo time scan that provides images similar to that of a CT scan. This will be done pre, immediately post, and 2-4 hours post inhaled prostacyclin therapy.

This study seeks to determine whether hyperpolarized 129Xenon MRI can detect improvements in pulmonary gas exchange in patients with Group 1 and 3 PH treated with iTRE. We will associate this with changes in serum concentrations of treprostinil and levels of peripheral vasodilation. This work seeks to apply and test a novel non-invasive methodology, hyperpolarized (HP) 129Xenon (Xe) magnetic resonance imaging (MRI), for the diagnosis of Pulmonary Vascular Disease. Hyperpolarized 129Xe MRI has been under active development and used in clinical research at Duke for over 7 years. If successful, 129Xe MRI could overcome the current limitations of PVD diagnosis while conferring a number of potential benefits. First, imaging the abnormalities in the lungs allows the diagnosis of PVD in the setting of concomitant heart or lung disease. With HP 129Xe MRI, abnormalities in gas exchange secondary to PVD can be directly visualized. Second, non-invasive diagnosis of PVD could remove the need for an invasive RHC. While RHC is a relatively safe procedure, there are a number of limitations to the interpretation of RHC, including arbitrary cutoffs for mPAP, PCWP, and PVR. Third, the abnormalities on HP 129Xe MRI could be used to non-invasively monitor response to therapy. If we are successful in demonstrating the applicability of HP 129Xe MRI, this technology holds the promise of greatly improving the diagnosis and management of PVD. This study will enroll ten patients with pulmonary hypertension (PH). The ten patients will be World Health Organization (WHO) PH classification Group 1 or out-of-proportion Group 3, with lung disease. These patient have been inhaled treprostinil (iTRE) as standard of care for their PH. Inhaled treprostinil (iTRE) is an FDA approved medication under the brand name of Tyvaso. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. The medication is delivered noninvasively, directly to the lungs using the approved ultrasonic nebulizer delivery system. Patients will take the inhaled treatment four times a day, about every four hours. The iTRE will be used to characterize their 129Xe MRI imaging, peripheral vasodilation and serum treprostinil concentration before and after treatment with iTRE. As iTRE has a plasma concentration half-life of \~ 45 minutes and time-to-peak concentration of 15 minutes, imaging done immediately before, 15 minutes after and 2-4 hours after drug treatment would potentially allow the visualization of changes in gas diffusion and peripheral vasodilation associated with iTRE. This is similar to changes seen in changes in ventilation in asthma after treatment with bronchodilators. Monitoring a later time point would also allow us to test whether vasodilation persists in the lung vasculature compared to the peripheral circulation. This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI techniques for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated to test gas exchange dynamics with high temporal resolution. The conventional 1H MRI scans will include a free-breathing ultra-short echo time (UTE) scan that provides images similar to that of a CT scan.

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Outcomes