title: Enabling hyperpolarized (129) Xe MR spectroscopy and imaging of pulmonary gas transfer to the red blood cells in transgenic mice expressing human hemoglobin.
abstract: OBJECTIVE
  Hyperpolarized (HP) (129) Xe gas in the alveoli can be detected separately from (129) Xe 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 (129) Xe MR. Here we overcome this limitation using a commercially available strain of transgenic mice that exclusively expresses human hemoglobin.
  
  
  METHODS
  Dynamic HP (129) Xe MR spectroscopy, and three-dimensional radial MRI of gaseous and dissolved (129) Xe were performed in both wild-type (C57BL/6) and transgenic mice.
  
  
  RESULTS
  Unlike wild-type animals, transgenic mice displayed two dissolved (129) Xe NMR peaks at 198 and 217 ppm, corresponding to (129) Xe 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.
  
  
  CONCLUSIONS
  It is now possible to examine the dynamics and spatial distribution of pulmonary gas uptake by the RBCs of mice using HP (129) Xe 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.
authors.affiliation: Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina, USA; Medical Physics Graduate Program, Duke University, Durham, North Carolina, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Freeman
authors.forename: Zackary I
authors.initials: ZI
authors.lastname: Cleveland
authors.forename: Yi
authors.initials: Y
authors.lastname: Qi
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Driehuys
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014979:Xenon Isotopes / Q000008:administration & dosage
chemical_list: D003287:Contrast Media; D006454:Hemoglobins; D019275:Radiopharmaceuticals; D014979:Xenon Isotopes
keywords: chemical shift saturation recovery; gas exchange; hyperpolarized 129Xe; interstitial lung disease; mouse model; red blood cell