Rationale: Studies demonstrating early structural lung damage in infants and preschool children with cystic fibrosis (CF) suggest that noninvasive monitoring will be important to identify patients who may benefit from early therapeutic intervention. Previous studies demonstrated that magnetic resonance imaging (MRI) detects structural and functional abnormalities in lungs from older patients with CF without radiation exposure. Objectives: To evaluate the potential of MRI to detect abnormal lung structure and perfusion in infants and preschool children with CF, and to monitor the response to therapy for pulmonary exacerbation. Methods: MRI studies were performed in 50 children with CF (age, 3.1 ± 2.1 yr; range, 0–6 yr) in stable clinical condition (n = 40) or pulmonary exacerbation before and after antibiotic treatment (n = 10), and in 26 non-CF control subjects (age, 2.9 ± 1.9 yr). T1- and T2-weighted sequences before and after intravenous contrast and first-pass perfusion imaging were acquired, and assessed on the basis of a dedicated morphofunctional score. Measurements and Main Results: MRI demonstrated bronchial wall thickening/bronchiectasis, mucus plugging, and perfusion deficits from the first year of life in most stable patients with CF (global score, 10.0 ± 4.0), but not in non-CF control subjects (score, 0.0 ± 0.0; P < 0.001). In patients with exacerbations, the global MRI score was increased to 18.0 ± 2.0 (P < 0.001), and was significantly reduced to 12.0 ± 3.0 (P < 0.05) after antibiotic therapy. Conclusions: MRI detected abnormalities in lung structure and perfusion, and response to therapy for exacerbations in infants and preschool children with CF. These results support the development of MRI for noninvasive monitoring and as an end point in interventional trials for early CF lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT00760071).

Rationale: Early onset and progression of lung disease in children with cystic fibrosis (CF) indicates that sensitive noninvasive outcome measures are needed for diagnostic monitoring and early intervention clinical trials. The lung clearance index (LCI) and chest magnetic resonance imaging (MRI) were shown to detect early lung disease in CF; however, the relationship between the two measures remains unknown. Objectives: To correlate the LCI with abnormalities detected by MRI and compare the sensitivity of the two techniques to detect responses to therapy for pulmonary exacerbations in children with CF. Methods: LCI determined by age-adapted multiple breath washout techniques and MRI studies were performed in 97 clinically stable children with CF across the pediatric age range (0.2–21.1 yr). Furthermore, LCI (n = 26) or MRI (n = 10) were performed at the time of pulmonary exacerbation and after antibiotic therapy. MRI was evaluated using a dedicated morphofunctional score. Measurements and Main Results: The LCI correlated with the global MRI score as well as MRI-defined airway wall abnormalities, mucus plugging, and abnormal lung perfusion in infants and toddlers (P < 0.05 to P < 0.001) and in older children (P < 0.001) with CF. LCI and MRI were sensitive to detect response to antibiotic therapy for pulmonary exacerbations. Conclusions: Our results indicate that LCI and MRI may be useful complementary tools for noninvasive monitoring and as quantitative endpoints in early intervention trials in children with CF. In this context, MRI enables detection of disease heterogeneity, including regional mucus plugging associated with abnormal lung perfusion in early CF lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 02270476).

Several randomized trials investigating the effectiveness of lung cancer screening with multislice computed tomography (MSCT) are under way in the United States¹ x 1 Aberle, DR, Adams, AM, Berg, CD et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. New Engl J Med. 2011; 365: 395–409 Crossref | PubMed | Scopus (3370) | Google Scholar See all References and Europe (reviewed in Refs. ² x 2 Saghir, Z, Dirksen, A, Ashraf, H et al. CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT. Thorax. 2012; 67: 296–301 Crossref | PubMed | Scopus (241) | Google Scholar See all References ^{, 3} x 3 Infante, M, Cavuto, S, Lutman, FR..., and DANTE Study Group. A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial. Am J Respir Crit Care Med. 2009; 180: 445–453 Crossref | PubMed | Scopus (266) | Google Scholar See all References ^{, 4} x 4 Lopes Pegna, A, Picozzi, G, Mascalchi, M..., and ITALUNG Study Research Group. Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with low-dose CT. Lung Cancer. 2009; 64: 34–40 Abstract | Full Text | Full Text PDF | PubMed | Scopus (185) | Google Scholar See all References ^{, 5} x 5 Pastorino, U, Rossi, M, Rosato, V et al. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012; 21: 308–315 Crossref | PubMed | Scopus (206) | Google Scholar See all References ^{, 6} x 6 Horeweg, N, van der Aalst, CM, Thunnissen, E et al. Characteristics of lung cancers detected by computer tomography screening in the randomized NELSON trial. Am J Respir Crit Care Med. 2013; 187: 848–854 Crossref | PubMed | Scopus (92) | Google Scholar See all References ^{, 7} x 7 Baldwin, DR, Duffy, SW, Wald, NJ, Page, R, Hansell, DM, and Field, JK. UK Lung Screen (UKLS) nodule management protocol: modelling of a single screen randomised controlled trial of low-dose CT screening for lung cancer. Thorax. 2011; 66: 308–313 Crossref | PubMed | Scopus (134) | Google Scholar See all References ^{, 8} x 8 Field, JK, van Klaveren, R, Pedersen, JH..., and European Randomized Screening Trial Group. European randomized lung cancer screening trials: post NLST. J Surg Oncol. 2013; 108: 280–286 Crossref | PubMed | Scopus (66) | Google Scholar See all References ) from which the American National Lung Screening Trial having provided first results.

Magnetic resonance imaging (MRI) of the lung is technically challenging due to the low proton density and fast signal decay of the lung parenchyma itself. Additional challenges consist of tissue loss, hyperinflation, and hypoxic hypoperfusion, e.g., in emphysema, a so-called "minus-pathology". However, pathological changes resulting in an increase of tissue ("plus-pathology"), such as atelectases, nodules, infiltrates, mucus, or pleural effusion, are easily depicted with high diagnostic accuracy. Although MRI is inferior or at best equal to multi-detector computed tomography (MDCT) for the detection of subtle morphological features, MRI now offers an increasing spectrum of functional imaging techniques such as perfusion assessment and measurement of ventilation and respiratory mechanics that are superior to what is possible with MDCT. Without putting patients at risk with ionizing radiation, repeated examinations allow for the evaluation of the course of lung disease and monitoring of the therapeutic response through quantitative imaging, providing a level of functional detail that cannot be obtained by any other single imaging modality. As such, MRI will likely be used for clinical applications beyond morphological imaging for many lung diseases. In this article, we review the technical aspects and protocol suggestions for chest MRI and discuss the role of MRI in the evaluation of nodules and masses, airway disease, respiratory mechanics, ventilation, perfusion and hemodynamics, and pulmonary vasculature.

Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40–50% of normal in patients with cystic fibrosis (CF) with one or two F508del alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. Objectives: To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two F508del alleles aged ⩾12 years. Methods: This prospective, observational, multicenter, postapproval study assessed LCI and lung MRI scores before and 8–16 weeks after initiation of ELX/TEZ/IVA. Measurements and Main Results: A total of 91 patients with CF, including 45 heterozygous for F508del and a minimal function mutation (MF) and 46 homozygous for F508del, were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in F508del/MF (−2.4; interquartile range [IQR], −3.7 to −1.1; P < 0.001) and F508del homozygous (−1.4; IQR, −2.4 to −0.4; P < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in F508del/MF (−6.0; IQR, −11.0 to −1.3; P < 0.001) and F508del homozygous (−6.5; IQR, −11.0 to −1.3; P < 0.001) patients. Conclusions: Our data demonstrate that improvement of CFTR function by ELX/TEZ/IVA improves lung ventilation and abnormalities in lung morphology, including airway mucus plugging and wall thickening, in adolescent and adult patients with CF and one or two F508del alleles in a real-world, postapproval setting. Clinical trial registered with www.clinicaltrials.gov (NCT04732910).