MR Imaging of Lung in the Follow-up Assessment of Cystic Fibrosis

Study Overview
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Brief Summary
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The aim of the study is to assess the diagnostic sensitivity of MRI to detect changes in Helbich-Bhalla scoring over time in patients with cystic fibrosis

Detailed Description
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Cystic fibrosis (CF) is caused by the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation and represents one of the most frequent and lethal inherited disease in Caucasian. However, thanks to better treatments that slow down the progression of pulmonary disease, the median life expectancy has reached 41 years and there are nowadays more CF patients older than 18-year-old than younger. Chronic lung disease is the main manifestation and represents more than 90% of CF morbidity and mortality. However, there is a need for biomarkers more sensitive than clinical and functional findings for a personalized management of patients. Computed tomography (CT), owing to its high spatial resolution and contrast, is the standard of reference in imaging for depicting lung structural alterations. But CT is an ionizing technique, rising concern in cancer risk associated to cumulated radiation dose. To date, Magnetic Resonance Imaging (MRI) is a radiation-free technique which has been demonstrated to add meaningful functional information that cannot be reached using CT. Recent advances in 3-dimensional ultra-short echo time (3D-UTE) imaging have been shown promising to improve lung MR imaging quality. A clear delineation between airway wall and lumen was obtained, thanks to submillimeter voxel size, enabling readers to estimate both bronchial thickening and dilatation with very good concordance with CT, independently from the magnitude of score. The combination of pulse sequence may rather benefit from the potential of MRI to get more complete insight into inflammatory processes by combining several contrasts, as compared to other ionizing methods. Novel MR methods have been shown promising in assessing lung changes with high resolution and therefore could be proposed instead of CT for radiation- free repeated, life-long follow-up

Official Title
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MR Imaging of Lung in the Follow-up Assessment of Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Device: lung MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female children (age ≥ 8 y.o) and adult patient with a diagnosis of cystic fibrosis provided by genetic and swear test older than 8 years. Subgroups of patients will be defined according to: age: younger or older 18y.o. We expect around 50% in different subgroups. In case of, we reach 50% in one of these groups, patient recruitment will continue for both groups until the expected number of patients in the study is reached. brand name of magnet: Siemens, General Electric or Philips new drugs use: association Ivacaftor/lumicaftor (OrkambiØ) or Ivacaftor only (Kalydeco Ø) ) We expect approximately 20% to 50% of patients treated Informed consent provided to the patient or/and to legal representative for adults and to parents for the children Patient concerned by articles L 1121-6, L 1121-7, and L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent) if the expected benefit for such persons justifies the foreseeable risk incurred Exclusion Criteria: patients without any social security or health insurance pregnant women Patients with previous pulmonary transplantation or planned for transplantation in the year following inclusion MRI contraindications:

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lung MRI<br>lung MRI without contrast injection | Device: lung MRI<br>* lung MRI without contrast injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of MRI to detect lung changes | deterioration or improvement measured by the Helbich-Bhalla scoring with CT as gold standard | Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of MRI to Helbich-Bhalla scoring change | Sensitivity of MRI to Helbich-Bhalla scoring change in various subgroups of patients according to age, centers and MR scan manufacturers, and new treatment drug use (Ivacaftor/lumicaftor: Orkambi Ø or Ivacaftor : Kalydeco Ø ) from CT and MR examinations | Month 0 and Month 36 | 
| CT / MR concordance | Concordance between CT and MR in amplitude of Helbich-Bhalla scoring variations at M0 and M36 | Month 0 and Month 36 | 
| Sensitivity of the 3D-UTE MR sequence | Sensitivity of the 3D-UTE MR sequence alone to detect change in Helbich-Bhalla scoring as compared to CT performed at M0 and M36 | Month 0 and Month 36 | 
| Imaging quality of the 3D-UTE MR | using a likert scale | Month 0, Month 12, Month 24 and Month 36 | 
| Correlation between a specific Helbich-Bhalla MR score and the amplitude of change | Correlation between a specific Helbich-Bhalla MR score with clinical and functional data, and concordance with the amplitude of change between M0 and M36 | Month 0 and Month 36 | 
| Accuracy of a lung MR protocol | Accuracy of a lung MR protocol including T1-weighted and T2-weighted sequences to diagnose allergic broncho-pulmonary aspergillosis (ABPA) in CF patients | Month 0 and Month 36 | 
| Reproducibility in detecting lung structural abnormality | MR and CT reproducibility in detecting lung structural abnormality at the segmental level | Month 0 and Month 36 | 
| Reproducibility in overall Helbich-Bhalla scoring | MR and CT reproducibility in overall Helbich-Bhalla scoring | Month 0 and Month 36 | 
| Correlations between Helbich-Bhalla scoring and clinical questionnaire | Correlations between Helbich-Bhalla scoring measured with MRI and CT and clinical questionnaire | Month 0 and Month 36 | 
| Correlations between Helbich-Bhalla scoring and exacerbation rate | Correlations between Helbich-Bhalla scoring measured with MRI and CT and exacerbation rate | Month 0 and Month 36 | 
| Correlations between Helbich-Bhalla scoring and clinical pulmonary functional test | Correlations between Helbich-Bhalla scoring measured with MRI and CT and clinical pulmonary functional test | Month 0 and Month 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CT, Cystic fibrosis, MRI, radiation dose, contrast agent