ORIGINAL RESEARCH Longitudinal Assessment of Patients With Cystic Fibrosis Lung Disease With Multivolume Noncontrast MRI and Spirometry Francesca Pennati, PhD, 1 * Irene Borzani, MD, 2 Laura Moroni, MD, 3 Maria Chiara Russo, MD, 3 Nadia Faelli, MD, 3 Andrea Aliverti, PhD, 1 and Carla Colombo, MD 3 Background: MRI has been suggested as a radiation-free imaging modality to investigate early structural alterations and regional functional impairment in cystic fibrosis (CF) lung disease. Purpose/Hypothesis: To compare functional and morphological MRI changes over the course of the disease to changes in spirometry. Study Type: Longitudinal retrospective study. Population: Twenty patients with CF lung disease (at baseline, age = 16.5 (13.3–20.6) years, forced expiratory volume in 1 second (as % of predicted [%pred]) FEV 1 = 71 (59–87) %pred, forced expiratory flow at 25–75% of forced vital capacity FEF 25-75 = 39 (25–63) %pred. Field Strength/Sequence: 1.5T / T 2 -weighted HASTE; T 2 -weighted TSE-PROPELLER; T 2 -weighted bSSFP; T 1 -weighted 3D GRE. Assessment: Nonenhanced chest MRI and spirometry were retrospectively collected over a 3-year period from the initial recruitment visit. Images acquired at end-inspiration and end-expiration were registered by software using the optical flow method to measure expiratory-inspiratory differences in MR signal-intensity (Δ 1 H-MRI). Measures of CF functional impair- ment were defined from Δ 1 H-MRI: Δ 1 H-MRI median, Δ 1 H-MRI quartile coefficient of variation (QCV), and percent low-sig- nal-variation volume (LVV). MR images were also evaluated by three readers using a CF-specific scoring system. Statistical Tests: Spearman correlation analysis, Spearman rank correlation analysis, linear mixed-effect model analysis, intraclass correlation coefficient. Results: Functional imaging parameters and total morphological score correlated with all spirometric measures, as did sub- scores of bronchial wall thickening/bronchiectasis, mucus plugging, and consolidation. Overall, the percent change of Δ1H-MRI median correlated with the percent change of FEV 1 (ΔFEV 1 , r= 0.41, P < 0.01) and the percent change of FEF 25-75 (ΔFEF25-75%, r= 0.38, P < 0.01). The percent change of LVV correlated with ΔFEV 1 (r= –0.47, P < 0.001) and ΔFEF 25-75 (r= –0.50, P < 0.001). Data Conclusion: These preliminary results suggest that nonenhanced multivolume MRI may provide a feasible tool to regionally map early pulmonary alterations for longitudinal evaluation of CF lung disease, without exposing the patients to ionizing radiation. Level of Evidence: 3T Technical Efficacy Stage: 5 J. MAGN. RESON. IMAGING 2020. F ORCED EXPIRATORY VOLUME IN 1 SECOND (FEV 1 ) is the primary outcome measure for characterizing lung function in patients with cystic fibrosis (CF) lung disease and evaluating the response to different kinds of treatment. 1,2 View this article online at wileyonlinelibrary.com. DOI: 10.1002/jmri.27461 Received Jun 4, 2020, Accepted for publication Nov 24, 2020. *Address reprint requests to: F.P., Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, P.zza L. da Vinci, 32, 20133 Milano, Italy. E-mail: francesca.pennati@polimi.it Contract grant sponsor: A.A and C.C. are recipients of a Vertex Innovation Award (VIA) 2017, which is an unconditional research grant provided by Vertex Phar- maceuticals. The funding body had no role in the design of the study, data collection, or in the writing of the article. From the 1 Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy; 2 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pediatric Radiology, Milan, Italy; and 3 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Centro Fibrosi Cistica, Milan, Italy © 2020 International Society for Magnetic Resonance in Medicine 1