Pulmonary function testing, the clinical gold standard for obtaining lung ventilation, provides only global information. Pulmonary hyperpolarized gas MRI (³He, ¹²⁹Xe) facilitates evaluation of regional lung ventilation at high signal-to-noise ratio with high spatial resolution. However, as ³He and ¹²⁹Xe lung MRI are typically single breathhold techniques, local lung ventilation may not be quantified in regions of slow washin kinetics (e.g. in emphysematous regions of COPD (chronic obstructive lung disease) patients), due to lack of inhaled gas in these lung regions after a single breath. Using fluorinated (¹⁹F) gas MRI to measure washin and washout kinetics by inhaling a mixture of the tracer gas with oxygen over several minutes may provide quantitative regional information of lung ventilation even in areas of slow washin or washout kinetics. Previously, ventilation dynamics using fluorinated gas MRI has been measured during breathholds each interleaved by several breathing cycles ¹. However, free breathing rather than repeated breathholds reflect normal lung physiology and real-time dynamic MR acquisition may increase accuracy as typical washin / washout times are in the range of several breathing cycles. Therefore, the purpose of this study was to quantify regional lung ventilation in COPD patients and normal volunteers using dynamic fluorinated gas MRI in free breathing and to correlate MRI-derived regional lung ventilation to parameters of the clinical lung function test.This study was approved by the local ethics committee. A human subject study using fluorinated gas MRI in free breathing was performed on a 1.5 T scanner (Siemens, Avanto) including 11 patients with COPD and 8 healthy volunteers. Dynamic ¹⁹F imaging was performed with a dedicated coil (Rapid Biomedical) tuned to 59.9 MHz consisting of a transmit Helmholtz coil and a 16 channel phased-array receive coil using a 3D spoiled gradient echo sequence (TE=5.1 ms, TR=12 ms, flip angle=50°, FOV=50x50x20 cm³, matrix size=64x64x6, bandwidth=140 Hz/pixel, GRAPPA factor=2). Each patient inhaled 30l of a mixture of 79% fluorinated gas (C₃F₈) and 21% oxygen via a closed face mask tubing and monitoring system as previously described ². Then, the subjects inhaled 100% O₂ and the measurement of the ¹⁹F wash-out dynamics was started. At post-processing, washout times in units of seconds (w_out[s]) and in number of breathing cycles (w_out[#breaths]) were determined in inspiration (insp) and expiration (exp) by mono-exponential fitting to the signal time series. Additionally, fractional ventilation (FV) was calculated using the following equation: FV=1-exp(-1/ w_out∙f_resp) (f_resp: mean respiratory frequency). For comparison with the current clinical gold standard, all patients with COPD underwent a lung function test.All COPD patients and healthy volunteers completed the ¹⁹F MRI exam without any side effects. Exemplary ¹⁹F gas images and washout maps of a healthy volunteer and a patient with COPD are shown in Figure 1 und Figure 2. Results for washout dynamics are presented in expiration due to lower variation compared to inspiration (coefficient of variation in volunteers for w_out[s]: insp: 0.35 / exp: 0.30; for w_out[#breaths]: insp: 0.31 / exp: 0.27; for FV: insp: 0.25 / exp: 0.19). Wilcoxon-Mann-Whitney test showed that for both w_out[s] and w_out[#breaths] washout time was significantly increased for patients with COPD (31.5±16.2 s; 6.6±2.8 breaths) compared to healthy volunteers (11.1±6.5 s; 2.0±0.6 breaths, p<0.001, Figure 3a and Figure 3b). In addition, FV was significantly reduced for patients with COPD (21.5±13.4 %) in comparison to healthy subjects (44.2±11.2 %) with p<0.001 (Figure 2c). For patients with COPD, the FV derived by dynamic fluorinated gas MRI correlated well with lung function test parameters (Spearman´s correlation coefficient) : forced expiratory volume at 1s (FEV1) r=0.77 (p<0.01) (Figure 4), FEV1 %/ forced vital capacity (FVC) r=0.74 (p=0.01) and ratio of forced expiratory flow (FEV) at 75% and 25% of FVC (FEV25-75%) r=0.80 (p<0.01).Dynamic fluorinated gas MRI in free breathing can measure impaired regional lung ventilation due to emphysema and air trapping in patients with COPD in comparison to healthy volunteers. The large range of washout times in patients with COPD compared to the healthy group can be explained by the different severity of lung disease in the COPD patient group. This is supported by the fact that the FV obtained by dynamic fluorinated gas MRI showed a strong positive correlation to FEV1, FEV1/VC and FEV25-75%, which are used in clinical routine to grade the severity of COPD (GOLD classification ³).The findings of this study show that dynamic fluorinated gas-washout MRI in free breathing allows detection and quantification of regional lung ventilation and thus adds significant value to the current clinical lung function test improving diagnosis and monitoring in COPD patients.