Rationale and Objectives
To assess the repeatability of global and regional lung ventilation quantification in both healthy subjects and patients with chronic obstructive pulmonary disease (COPD) using fluorinated ( 19 F) gas washout magnetic resonance (MR) imaging in free breathing.
Material and Methods
In this prospective institutional review board-approved study, 12 healthy nonsmokers and eight COPD patients were examined with 19 F dynamic gas washout MR imaging in free breathing and with lung function testing. Measurements were repeated within 2 weeks. Lung ventilation was quantified using 19 F gas washout time. Repeatability was analyzed for the total lung and on a regional basis using the coefficient of variation (COV) and Bland–Altman plots.
Results
In healthy subjects and COPD patients, a good repeatability was found for lung ventilation quantification using dynamic 19 F gas washout MR imaging on a global (COV < 8%) and regional (COV < 15%) level. Gas washout time was significantly increased in the COPD group compared to the healthy subjects.
Conclusion
19 F gas washout MR imaging provides a good repeatability of lung ventilation quantification and appears to be sensitive to early changes of regional lung function alterations such as normal aging.
Introduction
Functional pulmonary imaging to assess regional lung ventilation is a promising technique to further investigate lung diseases like chronic obstructive pulmonary disease (COPD) and asthma in order to improve its diagnosis and treatment. Since magnetic resonance imaging (MRI) is noninvasive, free of ionizing radiation, and offers several methods to probe lung function it has a high potential to be translated into clinical routine ( ).
Obviously, pulmonary gas MRI enables visualization of the respiratory tract and therefore provides regional information of lung ventilation ( ). To overcome the low signal-to-noise ratio (SNR) of gas MRI arising from the lower spin-density and higher diffusivity, mainly hyperpolarized gases are proposed as pulmonary gas tracers ( ). Alternatively, fluorinated ( 19 F) gases like sulfur hexafluoride (SF 6 ), tetrafluoromethane (CF 4 ), hexafluoroethane (C 2 F 6 ), and perfluoropropane (C 3 F 8 ) can be used at thermal polarization ( ). Fluorinated gases are nontoxic, chemically inert, and have a low solubility in water and blood. The relaxation of the fluorinated gases is dominated by spin–rotation interaction mediated by molecular collisions. Therefore, in a mixture with oxygen, which has a significantly lower molecular weight than the fluorinated gases, the collision rates increase and therefore T 1 and T 2 relaxation times of the fluorinated gases decrease with increasing concentration of oxygen ( ). Inhalation of a normoxic fluorinated gas mixture over several minutes did not show any adverse effects ( ). Their short longitudinal relaxation time T 1 (ranging from 1.8 ms for SF 6 up to 18 ms for C 3 F 8 at 1.5 T for the pure gas at room temperature and at atmospheric pressure) facilitates efficient 19 F gas MRI at short repetition times. Therefore, fluorinated gases provide sufficient SNR for pulmonary MRI in humans even at thermal polarization ( ).
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Material and Methods
Study Population
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Table 1
Study Population Information
ID Age (y)/(Sex) FVC (% pred.) FEV1 (% pred.) FEV1/FVC (%) a) Healthy volunteers H1 25 (f) 97.1 98.8 86.9 H2 38 (m) 100.1 99.2 79.8 H3 31 (m) 116.5 114.1 81.1 H4 27 (f) 102.6 107.0 88.4 H5 45 (m) 86.0 87.5 80.8 H6 24 (f) 100.9 108.1 92.5 H7 54 (m) 101.2 105.7 81.3 H8 69 (f) 124.8 119.5 74.0 H9 31 (m) 109.0 91.3 68.1 H10 49 (f) 99.4 104.7 84.5 H11 26 (m) 114.0 101.0 74.6 H12 35 (m) 88.4 95.2 87.2 b) COPD patients C1 60 (m) 81.5 55.3 52.3 C2 69 (m) 109.4 53.9 37.6 C3 72 (f) 78.3 58.3 57.2 C4 69 (m) 94.6 58.4 46.8 C5 76 (f) 81.8 61.5 57.6 C6 72 (m) 95.6 45.9 36.8 C7 76 (m) 84.0 56.5 51.3 C8 54 (f) 72.9 57.0 62.2
Spirometric data of scan day II are shown.
COPD, chronic obstructive disease; f, female; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; m, male; %pred, % predicted; y, years.
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MRI
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Image Analysis
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Statistical Analysis
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Results
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Table 2
Results of 19 F Gas Washout in Healthy Volunteers (a) and COPD Patients (b) Evaluated for the Total Lung
ID Exp: t washout (s) Insp: t washout (s) Insp: n washout (#breaths) Insp: FV washout (%) Exp: SNR Insp: SNR ΔFV washout (%/cm) a) Healthy volunteers H1 18.0 (4.9) 15.3 (4.3) 4.3 (1.2) 20.8 (5.0) 26.2 (32.0) 45.9 (24.6) 0.03 H2 30.9 (8.6) 26.1 (6.0) 4.3 (1.0) 20.6 (4.0) 30.7 (16.7) 46.4 (25.6) 0.38 H3 29.9 (5.6) 31.8 (4.3) 5.1 (0.7) 17.8 (2.1) 42.3 (32.3) 54.5 (28.9) 0.24 H4 20.4 (3.9) 16.1 (7.0) 2.7 (1.2) 30.7 (12.5) 48.9 (31.7) 55.3 (34.6) 0.58 H5 34.8 (14.0) 27.2 (9.2) 6.0 (2.0) 15.5 (4.7) 18.6 (10.1) 39.8 (16.2) −0.03 H6 25.7 (6.4) 22.7 (9.1) 3.7 (1.5) 23.8 (8.6) 42.3 (23.3) 43.5 (24.4) 0.51 H7 28.4 (7.6) 24.3 (6.6) 5.9 (1.6) 15.5 (4.0) 46.4 (23.9) 67.9 (28.6) 0.41 H8 46.3 (20.1) 41.2 (17.1) 7.5 (3.1) 12.4 (5.1) 49.8 (28.6) 67.6 (30.2) 0.22 H9 19.0 (6.2) 22.9 (6.7) 4.2 (1.2) 21.2 (5.6) 32.4 (15.5) 34.5 (11.8) 0.08 H10 10.5 (5.4) 10.0 (3.5) 2.1 (0.7) 38.5 (10.4) 18.5 (18.9) 35.5 (18.6) 0.75 H11 23.3 (7.3) 21.2 (6.0) 6.2 (1.7) 15.0 (3.8) 37.2 (21.3) 43.8 (19.7) 0.25 H12 15.8 (7.6) 15.8 (6.1) 3.4 (1.3) 25.7 (8.0) 21.6 (12.8) 27.0 (11.0) 0.41 All 24.5 (11.9) 22.8 (10.7) 4.3 (2.4) 20.7 (9.3) 34.8 (20.5) 44.9 (17.3) 0.32 (0.31) b) COPD patients C1 70.7 (76.1) 62.0 (59.8) 17.4 (17.7) 6.3 (5.2) 14.4 (7.0) 15.0 (6.2) C2 84.9 (25.4) 87.6 (73.7) 14.9 (5.9) 4.9 (3.4) 21.8 (10.7) 42.7 (21.4) C3 64.0 (37.9) 64.8 (50.4) 11.5 (5.7) 9.4 (7.0) 42.5 (23.0) 49.8 (25.0) C4 155.2 (100.1) 143.5 (135.7) 35.7 (22.3) 2.8 (2.3) 10.3 (4.0) 16.2 (7.3) C5 51.4 (55.4) 55.6 (24.6) 19.8 (16.6) 5.6 (4.2) 22.1 (8.2) 23.4 (11.1) C6 42.5 (34.4) 46.1 (33.1) 10.1 (8.0) 10.7 (8.5) 36.6 (22.8) 45.0 (27.0) C7 31.3 (47.1) 31.7 (32.4) 8.8 (11.4) 9.5 (8.5) 27.4 (11.8) 29.9 (11.8) C8 41.2 (22.4) 45.6 (26.3) 8.2 (4.8) 9.7 (5.3) 47.0 (23.9) 56.7 (28.4) All 57.7 (36.0) 58.8 (30.3) 13.2 (9.1) 7.9 (4.3) 24.8 (25.8) 36.3 (27.6)
Exp, expiration; FV washout , fractional ventilation; ID, identifier; Insp, inspiration; n washout , washout time in number of breaths; SNR: signal-to-noise ratio; t washout , washout time in units of seconds; ΔFV washout , gradient of fraction ventilation in anterior to posterior direction. Unless otherwise indicated data are median with interquartile range in brackets. Results of the first visit are shown.
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Healthy Subjects
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Table 3
Coefficient of Variation for 19 F Gas Washout Parameters Given in % Evaluated on a Regional Basis
Reg 1 Reg 2 Reg 3 Reg 4 Reg 5 Reg 6 Reg 7 Reg 8 Median a) Healthy volunteers_t_ washout 11.0 (11.4) 10.4 (12.3) 8.0 (6.3) 6.8 (6.0) 10.6 (4.5) 6.2 (7.6) 10.0 (11.8) 7.7 (15.6) 7.9 (9.2)n washout 8.4 (8.7) 6.2 (10.6) 4.0 (4.9) 5.4 (6.8) 5.1 (5.5) 4.7 (9.6) 4.9 (6.4) 8.8 (8.6) 5.6 (8.1) FV washout 7.8 (7.3) 5.7 (9.8) 3.5 (4.6) 4.9 (6.1) 4.7 (5.1) 4.2 (8.4) 4.4 (6.0) 7.8 (7.8) 5.0 (7.4) a) COPD patients_t_ washout 4.6 (3.6) 1.7 (10.4) 6.2 (4.2) 5.1 (10.4) 8.9 (16.4) 10.7 (10.2) 8.1 (6.6) 14.6 (13.4) 6.4 (10.8)n washout 3.6 (4.2) 5.9 (10.6) 7.6 (5.5) 5.6 (9.9) 11.5 (7.5) 5.5 (11.7) 6.5 (8.5) 12.4 (7.7) 7.1 (10.9) FV washout 3.3 (4.0) 5.6 (9.8) 7.0 (5.3) 5.3 (9.4) 10.5 (7.8) 5.3 (11.3) 6.2 (8.5) 11.9 (7.3) 6.8 (10.6)
FV washout , fractional ventilation; n washout , washout time in number of breaths; Reg, Region; t washout , washout time in units of seconds. Results are presented for the inspiratory lung volume.
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COPD Patients
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Comparison Between Study Groups
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Discussion
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