Morphologic and functional scoring of cystic fibrosis lung disease using MRI

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Abstract

Magnetic resonance imaging (MRI) gains increasing importance in the assessment of cystic fibrosis (CF) lung disease. The aim of this study was to develop a morpho-functional MR-scoring-system and to evaluate its intra- and inter-observer reproducibility and clinical practicability to monitor CF lung disease over a broad severity range from infancy to adulthood.

35 CF patients with broad age range (mean 15.3 years; range 0.5–42) were examined by morphological and functional MRI. Lobe based analysis was performed for parameters bronchiectasis/bronchial-wall-thickening, mucus plugging, abscesses/sacculations, consolidations, special findings and perfusion defects. The maximum global score was 72. Two experienced radiologists scored the images at two time points (interval 10 weeks). Upper and lower limits of agreement, concordance correlation coefficients (CCC), total deviation index and coverage probability were calculated for global, morphology, function, component and lobar scores.

Global scores ranged from 6 to 47. Intra- and inter-reader agreement for global scores were good (CCC: 0.98 (R1), 0.94 (R2), 0.97 (R1/R2)) and were comparable between high and low scores.

Our results indicate that the proposed morpho-functional MR-scoring-system is reproducible and applicable for semi-quantitative evaluation of a large spectrum of CF lung disease severity. This scoring-system can be applied for the routine assessment of CF lung disease and maybe as endpoint for clinical trials.

Introduction

Cystic fibrosis (CF) is caused by mutations in the CFTR gene and remains one of the most frequent lethal inherited diseases in Caucasians. Due to the progress in therapy and management of CF lung disease in the past decades, the life expectancy of CF patients has increased substantially, with a current median survival of ∼40 years [1], [2]. Given the improvement in prognosis, monitoring of disease progression and effectiveness of therapeutic interventions with repeated imaging of the CF lung plays an increasingly important role. So far, chest-x-ray is the most widely used imaging modality to monitor morphological changes in the CF lung. However, chest-x-ray has a limited sensitivity to detect early changes in the CF lung and is inferior to computed tomography (CT) [3]. CT has emerged as the “gold standard” for the assessment of morphological changes of the airways and lung parenchyma [4], [5], and is so far the only reliable imaging modality fulfilling the requirements for monitoring of early CF lung disease [6]. However, compared to chest-x-ray, chest CT implies a much higher radiation exposure. Considering the necessity of life-long repeated imaging studies, the cumulative radiation doses reached with CT could become problematic for CF patients, especially as their life expectancy increases further [7].

In previous studies, we demonstrated that magnetic resonance imaging (MRI) as a radiation free imaging modality proved to be comparable to CT regarding the detection of morphological changes in the CF lung without using ionising radiation [8]. Further, MRI was shown to be superior to CT regarding assessment of functional changes such as altered pulmonary perfusion [9]. For CT, the qualitative assessment of CF lung disease using scoring systems is well established [10], [11], [12]. More recently, quantification of morphological findings by CT became feasible and was successfully used in clinical trials. However, its application in clinical practice remains limited [13], [14]. For pulmonary MRI, both, a dedicated scoring system as well as quantitative assessment tools, are lacking. Although quantification of structural and functional abnormalities is desirable, the existing assessment tools are mostly individual, and not commercially available. Therefore, clinical practice relies on visual assessment. This forms the rationale for a visual MR scoring system comparable to the established CT scores [10], [11], [12]. However, although both techniques are cross sectional imaging modalities, they differ in their requirements for a visual scoring system. Compared to CT, MRI has a reduced spatial resolution, but allows for functional assessment and improved tissue characterisation [15]. Thus, besides morphology, functional parameters have to be resumed in a dedicated MR scoring system for CF lung disease. The prerequisite of a scoring system is its reproducibility requiring the highest possible inter- and intra-reader-agreement. An acceptable variance has to be defined before the scoring system is implemented for clinical use.

In this study, we developed and validated a dedicated MR scoring system for visual semi quantitative assessment of CF lung disease comprising the needs for morphological and functional MRI evaluation over broad age range from infancy to adult ages and assessed its intra- and inter-reader reproducibility.

Section snippets

Subjects

35 CF patients with stable CF lung disease were enrolled in the study. The diagnosis of CF was based on established diagnostic criteria including clinical symptoms consistent with CF, at least two positive sweat tests with sweat chloride concentrations > 60 mmol/l and/or detection of two disease causing mutations in the CFTR gene [16]. A broad age range of CF patients from infancy to adult ages (range 0.5–42 years, mean 15.3 years, median 15 years, Q1 8 years and Q3 20 years) was chosen to cover a wide

Results

All images were of diagnostic quality. The assessment and scoring time for morphological and functional images per patient did not exceed 10 min in any of the readers.

A broad spectrum of CF lung disease severity was covered, as reflected by global scores ranging from 6 to 47 points (from a maximum possible of 72).

Discussion

This study presents a new scoring system for the assessment of CF lung disease by morpho-functional MRI. We demonstrate that this dedicated MR-scoring system is reproducible for readers with experience in chest MRI.

This score aimed to cover morphological and functional changes in the CF lung over a wide range of disease severity from infancy to adulthood. To be integrated into the clinical diagnostic routine, this score had to be simple and easy to perform in a clinical setting.

The current

Conclusion

In summary, the presented scoring system is reproducible and provides an easy and quick MRI-assessment of morphology and function of a large spectrum of CF lung disease severity. Intra- and inter-observer agreement is good for experienced readers. Despite the above mentioned limitations, this first composite morphological and functional MR-score allows a more objective, regionally assessable and quantifiable comparison between examinations. This MR-scoring system can be applied for the routine

Support statement

This study was supported by the Mukoviszidose e.V. (S06/04 and S02/06) and the Deutsche Forschungsgemeinschaft (DFG MA 2081/4-1).

Acknowledgements

The authors acknowledge Dr. Matthias Wiebel (Department of Pulmonology, Thoraxklinik) and Dr. Julie Haeselbarth (Department of Pediatrics III, University Hospital Heidelberg) for patient recruitment, Prof. Heinz-Peter Schlemmer for reviewing the manuscript and the patients for their participation.

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