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Introduction The post modulator era is raising several new challenges, particularly with a need for sensitive pulmonary outcome measures (OM). Current tools are suboptimal; to address this our group developed MBW ShX to assess previously overlooked under ventilated lung units (UVLU), but it cannot provide spatial information. Functional lung MRI has the potential to be a sensitive OM to track CF lung disease. We hypothesised that in the context of improved clinical status, any lung disease progression would be observed more clearly using OE-MRI and MBWShX than conventional measures.Methods PwCF were recruited as part of a large observational study to determine the clinimetric properties of OE-MRI; all were on ETI therapy (>6 months at baseline). Participants performed OE-MRI, MBW ShX, and spirometry whilst clinically stable on the same day at baseline and at 6-monthly intervals over 18 months. OE-MRI parameters: ventilation defect percentage (VDP) and ∆R2* (ventilation signal). MBWShX parameters: UVLU and LCIShX (LCI2.5 + UVLU) a measure of global lung health. Data is presented as mean (SD) and ∆baseline (95%CI) and assessed using a mixed effects model with Dunnett’s test for multiple comparisons.Results Thirty-six pwCF aged 20.3 (±12.7) completed the baseline visit. FEV 1 and LCI2.5 appeared stable, whereas significant deterioration in the novel MBWShX and MRI parameters could be observed (table 1).Abstract S70 Table 1Pulmonary function parameters including values from oxygen enhanced (OE-)MRI at baseline, 6 months, 12 months and 18 months as well as deltas generated between follow up visits and the baseline visit Parameter Baseline (N=36) Mean (SD) 6 months (N=32) Mean (SD) ∆ (95%CI ) P value 12 months (N=32) Mean (SD) ∆ (95%CI ) P value 18 months (N=28) Mean (SD) ∆ (95%CI ) P value ppFEV1 89.5% (±19.4%) 88.9%(±19.2%) -0.5% (-3.8 to 2.7)P>0.05 88.7 (±19.7%) -0.8% (-4.0 to 2.4%)P>0.05 88.1% (±19.2%) -1.3% (-4.6 to 2.0%)P>0.05 LCI2.5 9.1 (±4.2) 9.1 (±4.0) 0.02 (-0.62 to 0.58)P>0.05 9.1 (±3.9) 0.02 (-0.61 to 0.57)P>0.05 9.4 (±3.9) 0.25 (-0.36 to 0.87)P>0.05 LCIShX 12.7 (±9.0) 13.3 (±9.8) 0.58 (-0.5 to 1.7)P>0.05 13.6 (±9.7) 0.91 (-0.2 to 2.0)P>0.05 14.2 (±8.5) 1.54 (0.5 to 2.53) P<0.01 UVLU 3.6 (±5.2) 4.2 (±6.3) 0.62 (-0.3 to1.6)P>0.05 4.5 (±6.0) 0.90 (0.03 to 1.74) P<0.05 4.7 (±4.6) 1.1 (0.2 to 1.98) P<0.01 ∆R2 * MS-1 0.076 (±0.025) 0.072 (±0.025) -0.004 (-0.010 to 0.002)P>0.05 0.069 (±0.025) -0.006 (-0.013 to 0.00) P<0.05 0.065 (±0.025) -0.011 (-0.017 to 0.00) P<0.001 VDP% 8.2% (±7.7%) 9.9% (±8.9%) 1.6% (0.3 to 3.6%) P>0.05 10.6% (±8.4%) 2.5% (0.6 to 4.4%) P <0.01 12.7% (±10.6%) 4.5% (2.5 to 6.6%) P <0.0001 Conclusions OE-MRI and MBW ShX are novel, sensitive markers of abnormalities in lung structure and function not detected by conventional outcomes (FEV1 and LCI2.5) and demonstrate potential as clinical outcome measures. Reliance on conventional OMs may lead to false reassurance about disease stability over time; particularly in relation to assessing safe withdrawal of standard treatments.Funded by CF Foundation.