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Ten years of chest MRI for patients with cystic fibrosis

Translation from the bench to clinical routine

10 Jahre Thorax-MRT für Patienten mit zystischer Fibrose

Übertragung vom Versuchsstadium in die klinische Routine

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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.

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Funding

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).

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Correspondence to Patricia Leutz-Schmidt.

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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.

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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

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