Background: Functional lung imaging offers insight into regional ventilation heterogeneity (VH) and can improve our assessment of COPD severity. X-ray velocimetry (XV) can assess lung segmental VH patterns but requires validation to standard measures and assessment of its clinical utility. 

Aim: Validate VH derived from XV against SPECT and determine associations between segmental VH and COPD symptom measures.

Methods: Participants with COPD and healthy controls were recruited from Johns Hopkins and the University of Miami. Segmental ventilation was assessed using XV(4DMedical) from fluoroscopy projections with CT overlay. SPECT was then performed with Tc-99m macro aggregated albumin, generating segmental ventilation for comparison. VH was derived from the distribution of segmental ventilation measures in XV and SPECT images, with scatter plots and Pearson coefficients to assess correlation. Sobel test determined associations between XV derived segmental VH and COPD symptoms (SGRQ) and mediation by FEV₁.

Results: Among 48 participants(35 COPD), mean age was 60 and mean FEV₁ was 51% predicted. There was moderate correlation between XV and SPECT derived VH (?=0.43, p=0.01). Higher segmental VH was correlated with worse SGRQ scores (?=0.54, p<0.01), with a persistent association after accounting for FEV1 (t'=82.4, p<0.01).

Conclusions: XV measures of segmental VH are associated with COPD severity and may hold promise as non-invasive biomarkers of COPD severity.