Rationale and Objectives
Hyperpolarized (HP) gas magnetic resonance imaging (MRI) is an advanced imaging technique that provides high-resolution regional information on lung function without using ionizing radiation. Before this modality can be considered for assessing clinical or investigational interventions, baseline repeatability needs to be established. We assessed repeatability of lung function measurement using HP helium-3 MRI (HP 3 He MRI) in a small cohort of patients with cystic fibrosis (CF).
Materials and Methods
We examined repeatability of HP 3 He MR images of five patients with CF in four scanning sessions over a 4-week period. We acquired images on a Philips 3.0 Tesla Achieva MRI scanner using a quadrature, flexible, wrap-around, 3 He radiofrequency coil with a fast gradient-echo pulse sequence. We determined ventilation volume and ventilation defect volume using an advanced semiautomatic segmentation algorithm and also quantified ventilation heterogeneity.
Results
There were no significant differences in total ventilation volume, ventilation defect volume, ventilation defect percentage, or mean ventilation heterogeneity (repeated-measures analysis of variance, P = .2116, P = .2825, P = .2871, and P = .7265, respectively) in the patients across the four scanning sessions.
Conclusions
Our results indicate that total ventilation volume, ventilation defect volume, ventilation defect percentage, and mean ventilation heterogeneity as assessed by HP gas MRI in CF patients with stable health are reproducible over time. This repeatability and the technique’s capability to provide noninvasive high-resolution data on regional lung function without ionizing radiation make 3 He MRI a potentially useful outcome measure for CF-related clinical trials.
Cystic fibrosis (CF) is a potentially fatal genetic disease caused by defects of the cystic fibrosis transmembrane conductance regulator (CFTR) protein coded by the CFTR gene, leading to impaired chloride ion transport . Although there have been major advances in CF health care over the past 20 years, CF still negatively affects quality of life and considerably shortens life expectancy, and thus there is still a desire for new CF therapies. It is acknowledged that improved end points for clinical trials are needed for further development of treatments .
Currently, the most common outcome measures for CF-related trials are pulmonary function tests (PFTs) to assess lung function and high-resolution computed tomography (HRCT) for anatomic imaging measurements. Other common study end points include frequency of pulmonary exacerbations, quality of life, and chest radiographs. All these measures are limited by not providing regional information on lung function and by being unable to detect subtle changes in function that could be used for early detection and assessment of therapy efficacy . There are exciting advances being made with CT imaging of structural changes in early-stage CF by the Australian Respiratory Early Surveillance Team (AREST) CF group in Australia , but the ionizing radiation associated with HRCT poses risks when used repeatedly over time, especially for young children . Additionally, PFTs and radiographs cannot detect early stages of lung disease or accurately measure the progression of disease . Therefore, there is a need for a measurement modality that can provide sensitive data on regional lung function, help assess status of lung disease at early stages, assist with care planning, and assess the efficacy of novel treatments, without the use of ionizing radiation .
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Material and methods
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Results
Evaluation of Repeatability
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Table 1
Pulmonary Function Test Data and HP 3 He Ventilation Imaging Data for the Five Patients for the Four Scanning Sessions (Week 0 = Baseline).
FEV 1 % NS FEV 1 NS FVC NS VV NS VDV NS VDP NS Subject 1 Week 0 98.00 3.40 4.25 4.19 0.29 6.37 Week 1 98.00 3.42 4.20 4.94 0.28 5.43 Week 2 96.00 3.35 4.11 4.16 0.28 6.41 Week 4 99.00 3.44 4.15 3.78 0.18 4.47 Subject 2 Week 0 70.00 2.95 3.81 4.38 0.49 10.10 Week 1 74.00 3.13 4.03 4.62 0.51 9.94 Week 2 72.00 3.03 3.98 4.38 0.58 11.62 Week 4 73.00 3.07 3.97 4.48 0.48 9.72 Subject 3 Week 0 63.00 3.18 4.63 4.06 0.92 18.48 Week 1 63.00 3.18 4.66 4.37 0.98 18.36 Week 2 67.00 3.37 4.97 4.49 1.13 20.09 Week 4 68.00 3.42 5.01 4.22 0.80 15.88 Subject 4 Week 0 72.00 2.04 3.01 3.50 0.42 10.69 Week 1 72.00 2.04 3.10 3.82 0.45 10.48 Week 2 70.00 2.00 3.16 4.05 0.36 8.17 Week 4 71.00 2.01 3.04 3.89 0.47 10.69 Subject 5 Week 0 105.00 4.43 5.09 5.64 0.42 7.00 Week 1 105.00 4.42 5.00 5.58 0.39 6.47 Week 2 111.00 4.69 5.28 5.28 0.30 5.31 Week 4 103.00 4.44 5.06 5.37 0.29 5.06
FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; VDP, ventilation defect percentage; VDV, ventilation defect volume; VV, total ventilation volume; NS, no significant difference found with repeated-measures analysis of variance.
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Comparison with Other Measures
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Discussion
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Acknowledgments
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