(141) Oxygen Enhanced-MRI (OE-MRI) and Multiple breath washout +/- Short extension (MBW_ShX) as novel functional assessments of CF lung health

Background: Poor sensitivity of spirometry and FEV₁ means the ‘gold standard’ for lung function testing in CF is suboptimal. Lung clearance index (LCI_2.5) derived from MBW is considered a good alternative but also has limitations. Addressing one of these, we recently developed an extension to MBW (MBW_ShX) to capture signal from previously overlooked under/un-ventilated lung units (UVLU)[1]. However, any MBW parameter will lack spatial information. OE-MRI provides a functional assessment of the lung on a spatial level, without the use of hyperpolarised gas or ionising radiation. The parameter reported here, R₂* enhancement, originates from the influence on the proton MRI signal of oxygen in the airways and dissolved within alveolar water and capillary blood. It thus represents a surrogate outcome combining ventilation, gas exchange and perfusion, with lower enhancement indicative of worse disease. We are conducting a longitudinal study to establish clinimetrics of these techniques; early cross-sectional data are reported here.

Methods: 20 CF subjects performed spirometry, MBW_ShX (Eco-medics Exhalyzer D, Spiroware software 3.3.1) & OE-MRI, on one day. MBW_ShX protocol: After the standard MBW ‘end of test’, subjects performed a slow vital capacity (SVC), followed by tidal breathing until ‘end of test’ criteria were re-met. Quantification of UVLU is calculated by change in N₂% resulting from the SVC, standardised for lung size. LCI_ShX (LCI_2.5 + UVLU) is a measure of global lung health, whereas UVLU is a standalone marker. The MRI protocol consisted of a dynamic series of multi-slice 2D dual echo radio frequency spoiled T₁-fast field echo sequences acquired with a temporal resolution of approx. 1.5 s during free breathing using a Siemens Aera 1.5 T scanner. The initial 60 acquisitions were obtained with medical air; the gas supply was then switched to 100% O₂ for 150 acquisitions, then returned to medical air for a final 150 acquisitions. Dynamic quantitative R₂* maps were calculated and the lung parenchyma, excluding central major vasculature, was manually segmented. Normally distributed parameters are presented as mean (±SD) & non-parametric parameters as median (range). Pearson’s (R) and Spearman’s (r) tests were used to assess correlations. P< 0.05 was considered significant.

Results: All 20 participants completed MBW_ShX and the OE-MRI protocol. Subjects were aged 13(±5.3) years with ppFEV₁ 92.2%(±12.3), ppFVC 98.8%(±11.2), LCI_2.5 7.5(6.3-15.6), LCI_ShX 9.0(6.1-31.0) and UVLU 1.2(-0.3-15.3). R₂* enhancement (0.087 ms^-1 (±0.017)) did not correlate with ppFEV₁ or ppFVC, but significant negative correlations were seen with LCI_2.5 (r -0.47, P< 0.05), LCI_­ShX(r -0.64, P< 0.01), and UVLU(r -0.67, P=0.001).

Conclusions: OE-MRI is feasible and tolerated by children as young as 7 years. Unlike spirometric values, LCI_2.5 correlated significantly with OE-MRI R₂*, again highlighting the superior sensitivity of MBW over FEV₁ in mild-moderate CF lung disease. Both novel MBW_ShX­ values also performed well; correlations with OE-MRI were numerically greater than that seen with LCI_2.5 although at this stage, we are not powered for statistical comparison. This ongoing project will assess short- and long-term repeatability of these novel assays, create a normative range, assess spatial heterogeneity and optimise MBW and OE-MRI parameters for use as future clinical and research outcomes.

Acknowledgements: This project was funded by the Cystic Fibrosis Foundation [Grant ID- 0208A120]

References: [1] Short et al, JCF. 2022; 21(1):146-154.