hyperpolarized xenon mri in cystic fibrosis pulmonary exacerbations

Conditions: Cystic Fibrosis

Summary: the investigators aim to assess whether pulmonary mri (hyperpolarised 129xe ventilation imaging \[xe-mri\]) can detect changes in ventilation defects in patients with cf before and after treatment for a pulmonary exacerbation. the investigators will determine whether changes seen using pulmonary xe-mri are associated with changes in pulmonary function (spirometry, lung volumes, lung clearance index \[lci\]) in patients with cf before and after pulmonary exacerbation.

cystic fibrosis (cf) is one of the most common genetic diseases affecting children and young adults \[1\]. lung disease is the primary cause of morbidity and mortality in these patients and sensitive markers of lung disease in cf are important for directing therapy in these patients. lci, measured by multiple breath washout (mbw), has been shown to be more sensitive than traditional pulmonary function tests (pfts) for assessing the treatment effect of novel therapies in cf patients \[2,3\]. however, lci provides no information regarding the spatial distribution of ventilation inhomogeneity within the lungs and improvements in mucus plugging of poorly ventilated regions can paradoxically worsen the lci \[4,5\]. thus an imaging technique that can capture regional changes in the distribution of ventilation might be better suited than lci to detect treatment effects and could also help to better define the utility of lci as a clinical tool. xe-mri is a safe, non-ionizing modality for imaging the lungs, providing an accurate spatial representation of ventilation inhomogeneity \[6\]. xe-mri has been shown to be effective in imaging of adult patients with chronic obstructive pulmonary disease (copd) and cf \[6\] however, there are no published studies using xe-mri in children. the hypothesis of this study is that xe-mri and lci will provide complimentary information when quantifying ventilation inhomogeneity in cf lung disease and that xe-mri will be able to define patients in whom lci fails to capture positive effects of treatment. the ultimate goal is to develop more sensitive tools for longitudinal monitoring to direct the clinical care of cf patients in the future. to accomplish this, the investigators will compare the ability of xe-mri and lci to detect changes in ventilation inhomogeneity in patients with cf before and after treatment for a pulmonary exacerbation, a common pulmonary complication of cf.

Eligibility criteria:
inclusion criteria: * diagnosis of cf as defined by two or more clinical features of cf and a documented sweat chloride \> 60meq/l by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations * informed consent and verbal assent (as appropriate) provided by the subject's parent or legal guardian and the subject * ages 8-18 years and able to perform reproducible spirometry and achieve a breath hold duration sufficient for mri acquisition * admission to the hospital for sick children for a pulmonary exacerbation (based on clinical or pulmonary function assessment). children who will be admitted and then discharged on home iv antibiotics may also be included in this study. exclusion criteria: * inability to perform reproducible pulmonary function tests (spirometry, plethysmography or lung clearance index) or perform a breath-hold of sufficient duration for mri acquisition * medical instability that would preclude the ability to undergo the required investigations * fev1 % predicted \< 40% * use of supplementary oxygen * severe claustrophobia * pregnancy or lactation * presence of metal implants or other contraindications to mri

Keywords: cf exacerbation hyerpolarized xenon mri pediatrics lung clearance index