Abstract
Background
Despite recent advances in our knowledge about the pathophysiology and treatment of cystic fibrosis (CF), pulmonary involvement remains the most important determinant of morbidity and mortality in patients with CF. Since lung function testing may not be sensitive enough for subclinical disease progression, and because young children may have normal spirometry results over a longer period of time, imaging today plays an increasingly important role in clinical routine and research for the monitoring of CF lung disease. In this regard, chest magnetic resonance imaging (MRI) could serve as a radiation-free modality for structural and functional lung imaging.
Methods
Our research agenda encompassed the entire process of development, implementation, and validation of appropriate chest MRI protocols for use with infant and adult CF patients alike.
Results
After establishing a general MRI protocol for state-of-the-art clinical 1.5-T scanners based on the available sequence technology, a semiquantitative scoring system was developed followed by cross-validation of the method against the established modalities of computed tomography, radiography, and lung function testing. Cross-sectional studies were then set up to determine the sensitivity of the method for the interindividual variation of the disease and for changes in disease severity after treatment. Finally, the MRI protocol was implemented at multiple sites to be validated in a multicenter setting.
Conclusion
After more than a decade, lung MRI has become a valuable tool for monitoring CF in clinical routine application and as an endpoint for clinical studies.
Zusammenfassung
Hintergrund
Trotz aktueller Fortschritte im Wissen über die Pathophysiologie und Behandlung der zystischen Fibrose (CF) bleibt die Lungenbeteiligung die wichtigste Determinante für Morbidität und Mortalität bei Patienten mit CF. Da die Lungenfunktionsprüfung möglicherweise nicht empfindlich genug ist, subklinisches Fortschreiten der Erkrankung anzuzeigen, und weil kleine Kinder über einen längeren Zeitraum normale Spirometrieergebnisse aufweisen können, spielt heutzutage die Bildgebung eine immer wichtigerer Rolle im klinischen Alltags- und Wissenschaftsbetrieb zur Überwachung der Lungenbeteiligung bei CF. Hierbei könnte die Magnetresonanztomographie (MRT) des Thorax als strahlungsfreie Modalität zur strukturellen und funktionellen Lungenbildgebung dienen.
Methoden
Das Forschungsprogramm der Autoren umfasste den gesamten Ablauf der Entwicklung, Etablierung und Validierung gleichermaßen geeigneter Thorax-MRT-Protokolle zum Einsatz bei CF-Patienten im Kindes- wie im Erwachsenenalter.
Ergebnisse
Nach Etablierung eines allgemeinen MRT-Protokolls für dem Stand der Technik entsprechende klinische 1,5-T-MRT-Geräte auf der Basis der verfügbaren Sequenztechnologie wurde ein semiquantitatives Punktesystem entwickelt mit anschließender Kreuzvalidierung der Methode gegen etablierte Verfahren wie Computertomographie, Röntgenuntersuchung und Lungenfunktionsprüfung. In Querschnittstudien wurde dann die Sensitivität der Methode für die interindividuelle Variation der Erkrankung und für Veränderungen der Krankheitsschwere nach Behandlung ermittelt. Schließlich wurde das MRT-Protokoll an mehreren Einrichtungen etabliert, um es in einer Multizenterstudie zu validieren.
Schlussfolgerung
Nach mehr als einem Jahrzehnt ist die MRT zu einem wertvollen Instrument für die Überwachung der CF im klinischen Alltag und zu einem Endpunkt in klinischen Studien geworden.
Similar content being viewed by others
References
Mall MA, Hartl D (2014) CFTR: cystic fibrosis and beyond. Eur Respir J 44:1042–1054
Stern M, Wiedemann B, Wenzlaff P (2008) From registry to quality management: the German Cystic Fibrosis Quality Assessment project 1995 2006. Eur Respir J 31:29–35
Sommerburg O, Stahl M, Hammermann J, Okun JG, Kulozik A, Hoffmann G, Mall M (2017) Newborn screening on cystic fibrosis in Germany: comparison of the new screening protocol with an alternative protocol. Klin Padiatr 229:59–66
Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, Murray CP, Stick SM (2013) Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 368:1963–1970
Wielputz MO, Eichinger M, Biederer J, Wege S, Stahl M, Sommerburg O, Mall MA, Kauczor HU, Puderbach M (2016) Imaging of cystic fibrosis lung disease and clinical interpretation. Rofo 188:834–845
Cleveland RH, Stamoulis C, Sawicki G, Kelliher E, Zucker EJ, Wood C, Zurakowski D, Lee E (2014) Brasfield and Wisconsin scoring systems have equal value as outcome assessment tools of cystic fibrosis lung disease. Pediatr Radiol 44:529–534
de Jong PA, Ottink MD, Robben SG, Lequin MH, Hop WC, Hendriks JJ, Pare PD, Tiddens HA (2004) Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements. Radiology 231:434–439
Kuo W, Ciet P, Tiddens HA, Zhang W, Guillerman RP, van Straten M (2014) Monitoring cystic fibrosis lung disease by computed tomography. Radiation risk in perspective. Am J Respir Crit Care Med 189:1328–1336
O’Connell OJ, McWilliams S, McGarrigle A, O’Connor OJ, Shanahan F, Mullane D, Eustace J, Maher MM, Plant BJ (2012) Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades. Chest 141:1575–1583
Kauczor HU, Heussel CP, Schreiber WG, Kreitner KF (2001) New developments in MRI of the thorax. Radiologe 41:279–287
Biederer J, Beer M, Hirsch W, Wild J, Fabel M, Puderbach M, Van Beek EJ (2012) MRI of the lung (2/3). Why ... when … how? Insights Imaging 3:355–371
Weatherly MR, Palmer CG, Peters ME, Green CG, Fryback D, Langhough R, Farrell PM (1993) Wisconsin cystic fibrosis chest radiograph scoring system. Pediatr Electron Pages 91:488–495
Bhalla M, Turcios N, Aponte V, Jenkins M, Leitman BS, McCauley DI, Naidich DP (1991) Cystic fibrosis: scoring system with thin-section CT. Radiology 179:783–788
Helbich TH, Heinz-Peer G, Eichler I, Wunderbaldinger P, Gotz M, Wojnarowski C, Brasch RC, Herold CJ (1999) Cystic fibrosis: CT assessment of lung involvement in children and adults. Radiology 213:537–544
Eichinger M, Optazaite DE, Kopp-Schneider A, Hintze C, Biederer J, Niemann A, Mall MA, Wielputz MO, Kauczor HU, Puderbach M (2012) Morphologic and functional scoring of cystic fibrosis lung disease using MRI. Eur J Radiol 81:1321–1329
Leutz-Schmidt P, Stahl M, Sommerburg O, Eichinger M, Puderbach MU, Schenk JP, Alrajab A, Triphan SMF, Kauczor HU, Mall MA, Wielputz MO (2018) Non-contrast enhanced magnetic resonance imaging detects mosaic signal intensity in early cystic fibrosis lung disease. Eur J Radiol 101:178–183
Puderbach M, Eichinger M, Haeselbarth J, Ley S, Kopp-Schneider A, Tuengerthal S, Schmaehl A, Fink C, Plathow C, Wiebel M, Demirakca S, Muller FM, Kauczor HU (2007) Assessment of morphological MRI for pulmonary changes in cystic fibrosis (CF) patients: comparison to thin-section CT and chest x‑ray. Invest Radiol 42:715–725
Puderbach M, Eichinger M, Gahr J, Ley S, Tuengerthal S, Schmahl A, Fink C, Plathow C, Wiebel M, Muller FM, Kauczor HU (2007) Proton MRI appearance of cystic fibrosis: comparison to CT. Eur Radiol 17:716–724
Wielputz MO, Puderbach M, Kopp-Schneider A, Stahl M, Fritzsching E, Sommerburg O, Ley S, Sumkauskaite M, Biederer J, Kauczor HU, Eichinger M, Mall MA (2014) Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med 189:956–965
Stahl M, Wielputz MO, Graeber SY, Joachim C, Sommerburg O, Kauczor HU, Puderbach M, Eichinger M, Mall MA (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 195:349–359
Wielputz MO, von Stackelberg O, Stahl M, Jobst BJ, Eichinger M, Puderbach MU, Nahrlich L, Barth S, Schneider C, Kopp MV, Ricklefs I, Buchholz M, Tummler B, Dopfer C, Vogel-Claussen J, Kauczor HU, Mall MA (2018) Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis. J Cyst Fibros 17:518–527
Wielputz M, Kauczor HU (2012) MRI of the lung: state of the art. Diagn Interv Radiol 18:344–353
Kauczor HUWMO (2018) MRI of the Lung. Springer, Berlin Heidelberg
Fink C, Ley S, Risse F, Eichinger M, Zaporozhan J, Buhmann R, Puderbach M, Plathow C, Kauczor HU (2005) Effect of inspiratory and expiratory breathhold on pulmonary perfusion: assessment by pulmonary perfusion magnetic resonance imaging. Invest Radiol 40:72–79
Eichinger M, Puderbach M, Fink C, Gahr J, Ley S, Plathow C, Tuengerthal S, Zuna I, Muller FM, Kauczor HU (2006) Contrast-enhanced 3D MRI of lung perfusion in children with cystic fibrosis—initial results. Eur Radiol 16:2147–2152
Kuder TA, Risse F, Eichinger M, Ley S, Puderbach M, Kauczor HU, Fink C (2008) New method for 3D parametric visualization of contrast-enhanced pulmonary perfusion MRI data. Eur Radiol 18:291–297
Risse F, Eichinger M, Kauczor HU, Semmler W, Puderbach M (2011) Improved visualization of delayed perfusion in lung MRI. Eur J Radiol 77:105–110
Eichinger M, Puderbach M, Heussel CP, Kauczor HU (2006) MRI in mucoviscidosis (cystic fibrosis). Radiologe 46:275–276, 278–281
Ley S, Puderbach M, Risse F, Ley-Zaporozhan J, Eichinger M, Takenaka D, Kauczor HU, Bock M (2007) Impact of oxygen inhalation on the pulmonary circulation: assessment by magnetic resonance (MR)-perfusion and MR-flow measurements. Invest Radiol 42:283–290
Hopkins SR, Wielputz MO, Kauczor HU (1985) Imaging lung perfusion. J Appl Physiol 113:328–339
Stern EJ, Muller NL, Swensen SJ, Hartman TE (1995) CT mosaic pattern of lung attenuation: etiologies and terminology. J Thorac Imaging 10:294–297
Sommerburg O, Hammermann J, Lindner M, Stahl M, Muckenthaler M, Kohlmueller D, Happich M, Kulozik AE, Stopsack M, Gahr M, Hoffmann GF, Mall MA (2015) Five years of experience with biochemical cystic fibrosis newborn screening based on IRT/PAP in Germany. Pediatr Pulmonol 50:655–664
Mall MA, Stahl M, Graeber SY, Sommerburg O, Kauczor HU, Wielputz MO (2016) Early detection and sensitive monitoring of CF lung disease: prospects of improved and safer imaging. Pediatr Pulmonol 51:S49–S60
Runge VM (2017) Critical questions regarding gadolinium deposition in the brain and body after injections of the gadolinium-based contrast agents, safety, and clinical recommendations in consideration of the EMA’s Pharmacovigilance and risk assessment committee recommendation for suspension of the marketing authorizations for 4 linear agents. Invest Radiol 52:317–323
Bauman G, Puderbach M, Deimling M, Jellus V, Chefd’hotel C, Dinkel J, Hintze C, Kauczor HU, Schad LR (2009) Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI. Magn Reson Med 62:656–664
Bauman G, Puderbach M, Heimann T, Kopp-Schneider A, Fritzsching E, Mall MA, Eichinger M (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 82:2371–2377
Nyilas S, Bauman G, Pusterla O, Ramsey K, Singer F, Stranzinger E, Yammine S, Casaulta C, Bieri O, Latzin P (2018) Ventilation and perfusion assessed by functional MRI in children with CF: reproducibility in comparison to lung function. J Cyst Fibros pii:S1569-1993(18)30854-3. https://doi.org/10.1016/j.jcf.2018.10.003
Kaireit TF, Sorrentino SA, Renne J, Schoenfeld C, Voskrebenzev A, Gutberlet M, Schulz A, Jakob PM, Hansen G, Wacker F, Welte T, Tümmler B, Vogel-Claussen J (2017) Functional lung MRI for regional monitoring of patients with cystic fibrosis. PLoS ONE 12:e187483
Triphan SM, Jobst BJ, Breuer FA, Wielputz MO, Kauczor HU, Biederer J, Jakob PM (2015) Echo time dependence of observed T1 in the human lung. J Magn Reson Imaging 42:610–616
Jobst BJ, Triphan SM, Sedlaczek O, Anjorin A, Kauczor HU, Biederer J, Ley-Zaporozhan J, Ley S, Wielputz MO (2015) Functional lung MRI in chronic obstructive pulmonary disease: comparison of T1 mapping, oxygen-enhanced T1 mapping and dynamic contrast enhanced perfusion. PLoS ONE 10:e121520
Stahl M, Wielputz MO, Kauczor HU, Mall MA (2018) Reply to Verbanck and Vanderhelst: the respective roles of lung clearance index and magnetic resonance imaging in the clinical management of patients with cystic fibrosis. Am J Respir Crit Care Med 197:410–411
Heidemann RM, Griswold MA, Kiefer B, Nittka M, Wang J, Jellus V, Jakob PM (2003) Resolution enhancement in lung 1H imaging using parallel imaging methods. Magn Reson Med 49:391–394
Mentore K, Froh DK, de Lange EE, Brookeman JR, Paget-Brown AO, Altes TA (2005) Hyperpolarized HHe 3 MRI of the lung in cystic fibrosis: assessment at baseline and after bronchodilator and airway clearance treatment. Acad Radiol 12:1423–1429
Smith L, Marshall H, Aldag I, Horn F, Collier G, Hughes D, West N, Horsley A, Taylor CJ, Wild J (2018) Longitudinal assessment of children with mild cystic fibrosis using hyperpolarized gas lung magnetic resonance imaging and lung clearance index. Am J Respir Crit Care Med 197:397–400
Jakob PM, Wang T, Schultz G, Hebestreit H, Hebestreit A, Hahn D (2004) Assessment of human pulmonary function using oxygen-enhanced T(1) imaging in patients with cystic fibrosis. Magn Reson Med 51:1009–1016
Ohno Y, Koyama H, Yoshikawa T, Seki S, Takenaka D, Yui M, Lu A, Miyazaki M, Sugimura K (2016) Pulmonary high-resolution ultrashort TE MR imaging: Comparison with thin-section standard- and low-dose computed tomography for the assessment of pulmonary parenchyma diseases. J Magn Reson Imaging 43:512–532
Wielputz MO, Triphan SMF, Ohno Y, Jobst BJ, Kauczor HU (2018) Outracing lung signal decay—potential of Ultrashort echo time MRI. Rofo 191(5):415–423. https://doi.org/10.1055/a-0715-2246
Kaireit TF, Voskrebenzev A, Gutberlet M, Freise J, Jobst B, Kauczor HU, Welte T, Wacker F, Vogel-Claussen J (2019) Comparison of quantitative regional perfusion-weighted phase resolved functional lung (PREFUL) MRI with dynamic gadolinium-enhanced regional pulmonary perfusion MRI in COPD patients. J Magn Reson Imaging 49:1122–1132
Fischer A, Weick S, Ritter CO, Beer M, Wirth C, Hebestreit H, Jakob PM, Hahn D, Bley T, Kostler H (2014) SElf-gated Non-Contrast-Enhanced FUnctional Lung imaging (SENCEFUL) using a quasi-random fast low-angle shot (FLASH) sequence and proton MRI. NMR Biomed 27:907–917
Funding
This study was supported in part by grants from the German Federal Ministry of Education and Research (82DZL00106, 82DZL001A6, 82DZL10201, 82DZL002A1, 82DZL00401, 82DZL004A1, 82DZL00501, 82DZL005A1). MAM was supported by the Einstein Foundation Berlin (EP-2017-393). ME, MUP, MS and MOW (C-H-P1504) received grants from the Christiane-Herzog-Stiftung and the Mukoviszidose e. V., the German Cystic Fibrosis Foundation. ME was supported by the Mukoviszidose e. V. (S06/04 and S02/06) and the Deutsche Forschungsgemeinschaft (DFG MA 2081/4-1). MUP was supported by the Forschungsgemeinschaft Mukoviszidose (S06/04). MS was supported by Mukoviszidose e. V. (grant 15/01).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. P. Leutz-Schmidt, M. Eichinger, M. Stahl, O. Sommerburg, J. Biederer, H.-U. Kauczor, M.U. Puderbach, M.A. Mall, and M.O. Wielpütz declare no conflicts of interest related to this work.
For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.
The supplement containing this article is not sponsored by industry.
Rights and permissions
About this article
Cite this article
Leutz-Schmidt, P., Eichinger, M., Stahl, M. et al. Ten years of chest MRI for patients with cystic fibrosis. Radiologe 59 (Suppl 1), 10–20 (2019). https://doi.org/10.1007/s00117-019-0553-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00117-019-0553-2