title: Measuring diffusion limitation with a perfusion-limited gas--hyperpolarized 129Xe gas-transfer spectroscopy in patients with idiopathic pulmonary fibrosis.
abstract: Although xenon is classically taught to be a "perfusion-limited" gas, (129)Xe in its hyperpolarized (HP) form, when detected by magnetic resonance (MR), can probe diffusion limitation. Inhaled HP (129)Xe diffuses across the pulmonary blood-gas barrier, and, depending on its tissue environment, shifts its resonant frequency relative to the gas-phase reference (0 ppm) by 198 ppm in tissue/plasma barrier and 217 ppm in red blood cells (RBCs). In this work, we hypothesized that in patients with idiopathic pulmonary fibrosis (IPF), the ratio of (129)Xe spectroscopic signal in the RBCs vs. barrier would diminish as diffusion-limitation delayed replenishment of (129)Xe magnetization in RBCs. To test this hypothesis, (129)Xe spectra were acquired in 6 IPF subjects as well as 11 healthy volunteers to establish a normal range. The RBC:barrier ratio was 0.55 ± 0.13 in healthy volunteers but was 3.3-fold lower in IPF subjects (0.16 ± 0.03, P = 0.0002). This was caused by a 52% reduction in the RBC signal (P = 0.02) and a 58% increase in the barrier signal (P = 0.01). Furthermore, the RBC:barrier ratio strongly correlated with lung diffusing capacity for carbon monoxide (DLCO) (r = 0.89, P < 0.0001). It exhibited a moderate interscan variability (8.25%), and in healthy volunteers it decreased with greater lung inflation (r = -0.78, P = 0.005). This spectroscopic technique provides a noninvasive, global probe of diffusion limitation and gas-transfer impairment and forms the basis for developing 3D MR imaging of gas exchange.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina; Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina; ssk13@duke.edu.
authors.forename: S Sivaram
authors.initials: SS
authors.lastname: Kaushik
authors.affiliation: Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina; Medical Physics Graduate Program, Duke University, Durham, North Carolina;
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Freeman
authors.affiliation: Medical Physics Graduate Program, Duke University, Durham, North Carolina;
authors.forename: Suk W
authors.initials: SW
authors.lastname: Yoon
authors.affiliation: University College London, London, United Kingdom;
authors.forename: Maria G
authors.initials: MG
authors.lastname: Liljeroth
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina; and.
authors.forename: Jane V
authors.initials: JV
authors.lastname: Stiles
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Justus E
authors.initials: JE
authors.lastname: Roos
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina; and.
authors.forename: W  Michael
authors.initials: W
authors.lastname: Foster
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rackley
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: H P
authors.initials: HP
authors.lastname: McAdams
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina; Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina; Medical Physics Graduate Program, Duke University, Durham, North Carolina; Department of Radiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Driehuys
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002248:Carbon Monoxide / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D011653:Pulmonary Diffusing Capacity; D011658:Pulmonary Fibrosis / Q000473:pathology* / Q000503:physiopathology; D015203:Reproducibility of Results; D012129:Respiratory Function Tests; D014979:Xenon Isotopes; D055815:Young Adult
chemical_list: D014979:Xenon Isotopes; D002248:Carbon Monoxide
keywords: diffusion limitation; gas-transfer spectroscopy; hyperpolarized 129Xe; idiopathic pulmonary fibrosis