Reproducibility of compartmental modelling of (18)F-FDG PET/CT to evaluate lung inflammation

INTRODUCTION: Compartmental modelling is an established method of quantifying (18)F-FDG uptake; however, only recently has it been applied to evaluate pulmonary inflammation. Implementation of compartmental models remains challenging in the lung, partly due to the low signal-to-noise ratio compared to other organs and the lack of standardisation. Good reproducibility is a key requirement of an imaging biomarker which has yet to be demonstrated in pulmonary compartmental models of (18)F-FDG; in this paper, we address this unmet need. METHODS: Retrospective subject data were obtained from the EVOLVE observational study: Ten COPD patients (age =66±9; 8M/2F), 10 α(1)ATD patients (age =63±8; 7M/3F) and 10 healthy volunteers (age =68±8; 9M/1F) never smokers. PET and CT images were co-registered, and whole lung regions were extracted from CT using an automated algorithm; the descending aorta was defined using a manually drawn region. Subsequent stages of the compartmental analysis were performed by two independent operators using (i) a MIAKAT(TM) based pipeline and (ii) an in-house developed pipeline. We evaluated the metabolic rate constant of (18)F-FDG (K(im)) and the fractional blood volume (V(b)); Bland-Altman plots were used to compare the results. Further, we adjusted the in-house pipeline to identify the salient features in the analysis which may help improve the standardisation of this technique in the lung. RESULTS: The initial agreement on a subject level was poor: Bland-Altman coefficients of reproducibility for K(im) and V(b) were 0.0031 and 0.047 respectively. However, the effect size between the groups (i.e. COPD, α(1)ATD and healthy subjects) was similar using either pipeline. We identified the key drivers of this difference using an incremental approach: ROI methodology, modelling of the IDIF and time delay estimation. Adjustment of these factors led to improved Bland-Altman coefficients of reproducibility of 0.0015 and 0.027 for K(im) and V(b) respectively. CONCLUSIONS: Despite similar methodology, differences in implementation can lead to disparate results in the outcome parameters. When reporting the outcomes of lung compartmental modelling, we recommend the inclusion of the details of ROI methodology, input function fitting and time delay estimation to improve reproducibility.