In Vivo MR Imaging of Pulmonary Perfusion and Gas Exchange in Rats via Continuous Extracorporeal Infusion of Hyperpolarized 129Xe

Background: Hyperpolarized (HP) Xe-129 magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (> 10%) and large chemical shift range (> 200 ppm) in tissues allow HP Xe-129 to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP Xe-129 in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP Xe-129 as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP Xe-129 signal. Methods and Principal Findings: Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse Xe-129 into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase Xe-129 signal is sufficient to generate diffusive gas exchange-and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2x2x2 mm(3). We also show that the Xe-129 signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. Conclusions: Extracorporeal infusion of HP Xe-129 enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow Xe-129 to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP Xe-129.