Enabling hyperpolarized ¹²⁹Xe MR spectroscopy and imaging of pulmonary gas transfer to the red blood cells in transgenic mice expressing human hemoglobin.

Freeman, Matthew S.; Cleveland, Zackary I.; Qi, Yi; Driehuys, Bastiaan

Purpose Hyperpolarized (HP) 129Xe gas in the alveoli can be detected separately from 129Xe dissolved in pulmonary barrier tissues (blood plasma and parenchyma) and red blood cells (RBCs) of humans, allowing this isotope to probe impaired gas uptake. Unfortunately, mice, which are favored as lung disease models, do not display a unique RBC resonance, thus limiting the preclinical utility of 129Xe MR. Here we overcome this limitation using a commercially available strain of transgenic mice that exclusively expresses human hemoglobin. Methods Dynamic HP 129Xe MR spectroscopy, and three-dimensional radial MRI of gaseous and dissolved 129Xe were performed in both wild-type (C57BL/6) and transgenic mice. Results Unlike wild-type animals, transgenic mice displayed two dissolved 129Xe NMR peaks at 198 and 217 ppm, corresponding to 129Xe dissolved in barrier tissues and RBCs, respectively. Moreover, signal from these resonances could be imaged separately, using a 1-point variant of the Dixon technique. Conclusion It is now possible to examine the dynamics and spatial distribution of pulmonary gas uptake by the RBCs of mice using HP 129Xe MR spectroscopy and imaging. When combined with ventilation imaging, this ability will enable translational 'mouse-to-human' studies of impaired gas exchange in a variety of pulmonary diseases. Magn Reson Med 70:1192-1199, 2013. © 2013 Wiley Periodicals, Inc.

Magnetic Resonance in Medicine, 2013, Vol 70, Issue 5, p1192

0740-3194

Academic Journal

10.1002/mrm.24915