129Xe magnetic resonance imaging for monitoring lung function and microstructure in patients on treatment for progressive fibrosing interstitial lung disease

<bold>Introduction:</bold> Novel antifibrotic therapy slows down lung function decline in patients with progressive fibrosing ILD (PF-ILD). While traditional lung function measures like FVC have limited sensitivity for early lung function alterations, more sensitive biomarkers for assessment of fibrosis progression and efficacy of new treatments are desirable. <bold>Aims and Objectives:</bold> The aim was to investigate the potential of hyperpolarized ¹²⁹Xe MR imaging markers for noninvasive assessment of disease progression in patients on antifibrotic therapy in an observational clinical trial. <bold>Methods:</bold> 14 PF-ILD patients underwent ¹²⁹Xe MRI and lung function testing at baseline and 3 and 6 months post initiation of clinically indicated antifibrotic therapy. MRI included dissolved-phase spectroscopy with frequency-selective excitation increasing signal from red blood cells (RBC) relative to membrane (M) to obtain averaged RBC:M and chemical shift saturation recovery (CSSR) quantifying dynamic ¹²⁹Xe uptake. CSSR data were analysed using MOXE to obtain surface-volume ratios (S/V). <bold>Results:</bold> Mean RBC:M was reduced at 6 months (P=0.01, –11%) and 3 months (P=0.04, –9%) vs. baseline. S/V was reduced at 6 months (P=0.007, –16%), but not 3 months (P=0.09, –13%). D_LCO (mmol/min/kPa) was reduced at 6 (P=0.01, –10%), but not 3 months (P=0.76, –2%). FVC (L) did not change (6 months: P=0.81, –2%, 3 months: P=0.22, +2%). <bold>Conclusions:</bold> RBC:M seems more sensitive to early changes of alveolar membrane function than D_LCO and FVC. S/V reduction is reflective of declining functional alveolar surface. RBC:M and S/V may be useful for monitoring PF-ILD patients on antifibrotic therapy.