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Updated: Jan 29, 2026

Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Airway Microstructure in Idiopathic Pulmonary Fibrosis: Assessment at Hyperpolarized 3He Diffusion-weighted MRI
Ho-Fung Chan1, Nicholas D Weatherley1, Christopher S Johns1
1From the POLARIS, Academic Unit of Radiology, Infection, Immunity and Cardiovascular Disease, University of Sheffield, C Floor, Royal Hallamshire Hospital, Glossop Rd, Sheffield, S10 2JF, England (H.F.C., N.D.W., C.S.J., N.J.S., G.J.C., J.M.W.); Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England (N.D.W., S.M.B.); and Department of Radiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England (C.S.J.).
Abstract:
Background MRI with inhaled hyperpolarized helium 3 (3He) allows for functional and structural imaging of the lungs. Hyperpolarized gas diffusion-weighted (DW) MRI provides noninvasive and quantitative assessment of microstructural acinar changes in the lungs. Purpose To investigate whether microstructural imaging metrics from in-vivo hyperpolarized 3He DW MRI are sensitive to longitudinal changes in a cohort of participants with idiopathic pulmonary fibrosis (IPF) and to evaluate the reproducibility of these metrics and their correlation with existing clinical measures of IPF disease severity. Materials and Methods In this prospective study, 18 participants with IPF underwent 3He DW MRI at 1.5 T and 11 participants underwent an identical same-day examination for reproducibility assessment. Thirteen participants returned for 6- and 12-month follow-up examinations. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide and forced vital capacity, were performed at each examination. The apparent diffusion coefficient (ADC) and stretched exponential model-derived mean diffusive length scale (LmD) from DW MRI was compared with baseline CT fibrosis scores and pulmonary function tests by using Spearman rank correlation coefficient. Longitudinal changes in DW MRI and pulmonary function test measurements were assessed with Friedman tests and post hoc Dunn test. Results 3He ADC and LmD were reproducible (mean Bland-Altman analysis bias, 0.002 cm2 · sec-1 and -1.5 microm, respectively). Elevated ADC and LmD regions qualitatively corresponded to fibrotic regions at CT. ADC and LmD correlated with diffusing capacity of the lungs for carbon monoxide (respectively: r = -0.56, P = .017; and r = -0.54, P = .02) and CT fibrosis score (respectively: r = 0.71, P = .001; and r = 0.65, P = .003). LmD increased by 12 microm after 12 months (P = .001) whereas mean ADC (P = .17), forced vital capacity (P = .12), and diffusing capacity of the lungs for carbon monoxide (P > .99) were not statistically different between examinations. Conclusion Helium 3 diffusion-weighted MRI-derived mean diffusive length scale demonstrates longitudinal changes in lungs affected by idiopathic pulmonary fibrosis. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Altes and Flors in this issue.
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