title: 3D MRI of impaired hyperpolarized 129Xe uptake in a rat model of pulmonary fibrosis.
abstract: A variety of pulmonary pathologies, in particular interstitial lung diseases, are characterized by thickening of the pulmonary blood-gas barrier, and this thickening results in reduced gas exchange. Such diffusive impairment is challenging to quantify spatially, because the distributions of the metabolically relevant gases (CO2 and O2) cannot be detected directly within the lungs. Hyperpolarized (HP) (129)Xe is a promising surrogate for these metabolic gases, because MR spectroscopy and imaging allow gaseous alveolar (129)Xe to be detected separately from (129)Xe dissolved in the red blood cells (RBCs) and the adjacent tissues, which comprise blood plasma and lung interstitium. Because (129)Xe reaches the RBCs by diffusing across the same barrier tissues (blood plasma and interstitium) as O2, barrier thickening will delay (129)Xe transit and, thus, reduce RBC-specific (129)Xe MR signal. Here we have exploited these properties to generate 3D, MR images of (129)Xe uptake by the RBCs in two groups of rats. In the experimental group, unilateral fibrotic injury was generated prior to imaging by instilling bleomycin into one lung. In the control group, a unilateral sham instillation of saline was performed. Uptake of (129)Xe by the RBCs, quantified as the fraction of RBC signal relative to total dissolved (129)Xe signal, was significantly reduced (P = 0.03) in the injured lungs of bleomycin-treated animals. In contrast, no significant difference (P = 0.56) was observed between the saline-treated and untreated lungs of control animals. Together, these results indicate that 3D MRI of HP (129)Xe dissolved in the pulmonary tissues can provide useful biomarkers of impaired diffusive gas exchange resulting from fibrotic thickening.
authors.affiliation: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Zackary I
authors.initials: ZI
authors.lastname: Cleveland
authors.forename: Rohan S
authors.initials: RS
authors.lastname: Virgincar
authors.forename: Yi
authors.initials: Y
authors.lastname: Qi
authors.forename: Scott H
authors.initials: SH
authors.lastname: Robertson
authors.forename: Simone
authors.initials: S
authors.lastname: Degan
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Driehuys
mesh_terms: D000818:Animals; D001761:Bleomycin; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D021621:Imaging, Three-Dimensional; D008168:Lung / Q000473:pathology; D008279:Magnetic Resonance Imaging; D011658:Pulmonary Fibrosis / Q000175:diagnosis* / Q000473:pathology; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012815:Signal Processing, Computer-Assisted; D012965:Sodium Chloride; D013057:Spectrum Analysis; D014979:Xenon Isotopes
chemical_list: D014979:Xenon Isotopes; D001761:Bleomycin; D012965:Sodium Chloride
keywords: Dixon imaging; ILD; IPF; chemical shift; diffusion impairment; gas exchange; interstitial lung disease; xenon-129