New severity assessment in cystic fibrosis: signal intensity and lung volume compared to LCI and FEV1: preliminary results

  • Sabrina Fleischer
  • Mareen Sarah KrausEmail author
  • Sergios Gatidis
  • Winfried Baden
  • Andreas Hector
  • Dominik Hartl
  • Ilias Tsiflikas
  • Juergen Frank Schaefer



Magnetic resonance imaging (MRI) aids diagnosis in cystic fibrosis (CF) but its use in quantitative severity assessment is under research. This study aims to assess changes in signal intensity (SI) and lung volumes (Vol) during functional MRI and their use as a severity assessment tool in CF patients.


The CF intra-hospital standard chest 1.5 T MRI protocol comprises of very short echo-time sequences in submaximal in- and expiration for functional information. Quantitative measurements (Vol/SI at in- and expiration, relative differences (Vol_delta/SI_delta), and cumulative histograms for normalized SI values across the expiratory lung volume) were assessed for correlation to pulmonary function: lung clearance index (LCI) and forced expiratory volume in 1 s (FEV1).


In 49 patients (26 male, mean age 17 ± 7 years) significant correlation of Vol_delta and SI_delta (R = 0.86; p < 0.0001) during respiration was observed. Individual cumulated histograms enabled severity disease differentiation (mild, severe) to be visualized (defined by functional parameter: LCI > 10). The expiratory volume at a relative SI of 100% correlated significantly to LCI (R = 0.676 and 0.627; p < 0.0001) and FEV1 (R = − 0.847 and − 0.807; p < 0.0001). Clustering patients according to Vol_SI_100 showed that an amount of ≤ 4% was related to normal, while an amount of > 4% was associated with pathological pulmonary function values.


Functional pulmonary MRI provides a radiation-free severity assessment tool and can contribute to early detection of lung impairment in CF. Lung volume with SI below 100% of the inspiratory volume represents overinflated tissue; an amount of 4% of the expiratory lung volume was a relevant turning point.

Key Points

• Signal intensity and lung volumes are used as potential metric parameters for lung impairment.

• Quantification of trapped air impacts on therapy management.

• Functional pulmonary MRI can contribute to early detection of lung impairment.


Pediatrics Pulmonary cystic fibrosis Lung volume measurements Functional magnetic resonance imaging Respiratory function tests 



Cystic fibrosis


Computer tomography


Forced expiratory volume in 1 s


Lung clearance index


Magnetic resonance imaging


Pulmonary function test


Signal intensity


Signal intensity/volume difference between in- and expiration


In-/expiratory signal intensity


Lung volumetry



We would like to separately acknowledge with gratitude the substantial work of the late Dr. Riethmueller toward this project and his meaningful close collaboration. We would also like to thank Dr. Andrew Dickinson for his help editing this manuscript.

Funding information

The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is Prof. JF Schäfer.

Conflict of interest

The authors declare that they have no conflict of interest.

Statistics and biometry

One of the authors has significant statistical expertise and no complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all patients in this study.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• diagnostic study

• performed at one institution

Supplementary material

330_2019_6462_MOESM1_ESM.docx (5.6 mb)
ESM 1 (DOCX 5736 kb)


  1. 1.
    O’Sullivan BP, Freedman SD (2009) Cystic fibrosis. Lancet 373(9678):1891–1904. CrossRefPubMedGoogle Scholar
  2. 2.
    Kerem E, Reisman J, Corey M, Canny GJ, Levison H (1992) Prediction of mortality in patients with cystic fibrosis. N Engl J Med 326(18):1187–1191. CrossRefPubMedGoogle Scholar
  3. 3.
    Horsley A (2009) Lung clearance index in the assessment of airways disease. Respir Med 103(6):793–799. CrossRefPubMedGoogle Scholar
  4. 4.
    VanDevanter DR, Wagener JS, Pasta DJ et al (2010) Pulmonary outcome prediction (POP) tools for cystic fibrosis patients. Pediatr Pulmonol 45(12):1156–1166. CrossRefGoogle Scholar
  5. 5.
    Kraemer R, Blum A, Schibler A, Ammann RA, Gallati S (2005) Ventilation inhomogeneities in relation to standard lung function in patients with cystic fibrosis. Am J Respir Crit Care Med 171(4):371–378. CrossRefPubMedGoogle Scholar
  6. 6.
    Gustafsson PM, Aurora P, Lindblad A (2003) Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis. Eur Respir J 22(6):972–979CrossRefGoogle Scholar
  7. 7.
    Ellemunter H, Fuchs SI, Unsinn KM et al (2010) Sensitivity of lung clearance index and chest computed tomography in early CF lung disease. Respir Med 104(12):1834–1842. CrossRefGoogle Scholar
  8. 8.
    Schaefer JF, Hector A, Schmidt K et al (2017) A semiquantitative MRI-score can predict loss of lung function in patients with cystic fibrosis: preliminary results. Eur Radiol. CrossRefGoogle Scholar
  9. 9.
    Owens CM, Aurora P, Stanojevic S et al (2011) Lung clearance index and HRCT are complementary markers of lung abnormalities in young children with CF. Thorax 66(6):481–488. CrossRefGoogle Scholar
  10. 10.
    Wielputz MO, Mall MA (2015) Imaging modalities in cystic fibrosis: emerging role of MRI. Curr Opin Pulm Med 21(6):609–616. CrossRefPubMedGoogle Scholar
  11. 11.
    Teufel M, Ketelsen D, Fleischer S et al (2013) Comparison between high-resolution CT and MRI using a very short echo time in patients with cystic fibrosis with extra focus on mosaic attenuation. Respiration 86(4):302–311. CrossRefGoogle Scholar
  12. 12.
    Biederer J, Heussel CP, Puderbach M, Wielpuetz MO (2014) Functional magnetic resonance imaging of the lung. Semin Respir Crit Care Med 35(1):74–82. CrossRefPubMedGoogle Scholar
  13. 13.
    Bauman G, Puderbach M, Heimann T et al (2013) Validation of Fourier decomposition MRI with dynamic contrast-enhanced MRI using visual and automated scoring of pulmonary perfusion in young cystic fibrosis patients. Eur J Radiol 82(12):2371–2377. CrossRefGoogle Scholar
  14. 14.
    Morbach AE, Gast KK, Schmiedeskamp J et al (2006) Microstructure of the lung: diffusion measurement of hyperpolarized 3Helium. Z Med Phys 16(2):114–122Google Scholar
  15. 15.
    Boss A, Schaefer S, Martirosian P, Claussen CD, Schick F, Schaefer JF (2008) Magnetic resonance imaging of lung tissue: influence of body positioning, breathing and oxygen inhalation on signal decay using multi-echo gradient-echo sequences. Invest Radiol 43(6):433–438. CrossRefPubMedGoogle Scholar
  16. 16.
    Puderbach M, Eichinger M, Gahr J et al (2007) Proton MRI appearance of cystic fibrosis: comparison to CT. Eur Radiol 17(3):716–724. CrossRefGoogle Scholar
  17. 17.
    Zapke M, Topf HG, Zenker M et al (2006) Magnetic resonance lung function--a breakthrough for lung imaging and functional assessment? A phantom study and clinical trial. Respir Res 7:106.
  18. 18.
    Sheikh K, Guo F, Capaldi DP et al (2017) Ultrashort echo time MRI biomarkers of asthma. J Magn Reson Imaging 45(4):1204–1215. CrossRefGoogle Scholar
  19. 19.
    Fuchs SI, Ellemunter H, Eder J et al (2012) Feasibility and variability of measuring the lung clearance index in a multi-center setting. Pediatr Pulmonol 47(7):649–657. CrossRefGoogle Scholar
  20. 20.
    Fuchs SI, Eder J, Ellemunter H, Gappa M (2009) Lung clearance index: normal values, repeatability, and reproducibility in healthy children and adolescents. Pediatr Pulmonol 44(12):1180–1185. CrossRefPubMedGoogle Scholar
  21. 21.
    Plathow C, Schoebinger M, Fink C et al (2005) Evaluation of lung volumetry using dynamic three-dimensional magnetic resonance imaging. Invest Radiol 40(3):173–179CrossRefGoogle Scholar
  22. 22.
    Bankier AA, O’Donnell CR, Mai VM et al (2004) Impact of lung volume on MR signal intensity changes of the lung parenchyma. J Magn Reson Imaging 20(6):961–966. CrossRefGoogle Scholar
  23. 23.
    Bauman G, Pusterla O, Santini F, Bieri O (2018) Dynamic and steady-state oxygen-dependent lung relaxometry using inversion recovery ultra-fast steady-state free precession imaging at 1.5 T. Magn Reson Med 79(2):839–845. CrossRefGoogle Scholar
  24. 24.
    Dorlochter L, Nes H, Fluge G, Rosendahl K (2003) High resolution CT in cystic fibrosis--the contribution of expiratory scans. Eur J Radiol 47(3):193–198CrossRefGoogle Scholar
  25. 25.
    Kanhere N, Couch MJ, Kowalik K et al (2017) Correlation of LCI with hyperpolarized 129Xe magnetic resonance imaging in pediatric CF subjects. Am J Respir Crit Care Med. CrossRefGoogle Scholar
  26. 26.
    Altes TA, Meyer CH, Mata JF et al (2017) Hyperpolarized helium-3 magnetic resonance lung imaging of non-sedated infants and young children: a proof-of-concept study. Clin Imaging 45:105–110. CrossRefGoogle Scholar
  27. 27.
    Lamarre A, Reilly BJ, Bryan AC, Levison H (1972) Early detection of pulmonary function abnormalities in cystic fibrosis. Pediatrics 50(2):291–298PubMedGoogle Scholar
  28. 28.
    Leutz-Schmidt P, Stahl M, Sommerburg O et al (2018) Non-contrast enhanced magnetic resonance imaging detects mosaic signal intensity in early cystic fibrosis lung disease. Eur J Radiol 101:178–183. CrossRefGoogle Scholar
  29. 29.
    Tepper LA, Ciet P, Caudri D, Quittner AL, Utens EM, Tiddens HA (2016) Validating chest MRI to detect and monitor cystic fibrosis lung disease in a pediatric cohort. Pediatr Pulmonol 51(1):34–41. CrossRefPubMedGoogle Scholar
  30. 30.
    Stahl M, Wielputz MO, Graeber SY et al (2017) Comparison of lung clearance index and magnetic resonance imaging for assessment of lung disease in children with cystic fibrosis. Am J Respir Crit Care Med 195(3):349–359.
  31. 31.
    Veldhoen S, Weng AM, Knapp J et al (2017) Self-gated non-contrast-enhanced functional lung MR imaging for quantitative ventilation assessment in patients with cystic fibrosis. Radiology 283(1):242–251. CrossRefGoogle Scholar
  32. 32.
    Svedberg M, Gustafsson PM, Robinson PD, Rosberg M, Lindblad A (2017) Variability of lung clearance index in clinically stable cystic fibrosis lung disease in school age children. J Cyst Fibros. CrossRefGoogle Scholar
  33. 33.
    Kligerman SJ, Henry T, Lin CT, Franks TJ, Galvin JR (2015) Mosaic attenuation: etiology, methods of differentiation, and pitfalls. Radiographics 35(5):1360–1380. CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  1. 1.Department of Diagnostic and Interventional RadiologyUniversity Hospital TuebingenTuebingenGermany
  2. 2.Department of PediatricsUniversity Hospital TuebingenTuebingenGermany

Personalised recommendations