Abstract
BackgroundHyperpolarized (HP) 129Xe 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 129Xe 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 129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP 129Xe 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 129Xe signal.Methods and Principal FindingsHere, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse 129Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase 129Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm3. We also show that the 129Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation.ConclusionsExtracorporeal infusion of HP 129Xe 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 129Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP 129Xe.
Highlights
The hyperpolarized (HP) noble gases 3He and 129Xe [1,2] have emerged as promising contrast agents for magnetic resonance imaging (MRI) of pulmonary structure and function
Xenon is soluble in tissues [6], and 129Xe possesses a large (.200 ppm) chemical shift range, making it a powerful probe of the local chemical environment within biological systems [7,8,9], and these properties can be exploited to directly image gas uptake in the lungs of rodents [10] and humans [11,12]
Physiological Effects of HP 129Xe EC Infusion In preliminary bench-top experiments, room temperature hetastarch was used to prime the EC circuit, but this sometimes led to severe reductions in body temperature and, occasionally, to the death of the animal
Summary
The hyperpolarized (HP) noble gases 3He and 129Xe [1,2] have emerged as promising contrast agents for magnetic resonance imaging (MRI) of pulmonary structure and function. Its reasonably high solubility (.10%) and large chemical shift range (.200 ppm) in tissues allow HP 129Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. Vascular delivery was accomplished in rats by first dissolving HP 129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and detecting HP 129Xe as it emerged into the alveolar airspaces. Implemented, this approach was constrained by the tolerable injection volume and the duration of the HP 129Xe signal
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