Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers

Abstract

Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility.

Fig. 1.

Dynamic time–attenuation curve data for an SNI subject. Graphs show corresponding time–attenuation curves demonstrating the dynamic change in HU as the bolus of contrast passes through the PA (Upper) and through the dependent and nondependent regions of the lung parenchyma (Lower). Regional PBF and MTT are obtained by applying indicator dilution theory to the data. (Inset) MDCT perfusion baseline image.

Fig. 2.

Color-coded maps of perfusion parameters overlaid on an imaging slice for a subject in each group. (A) MTT maps for NS (Left), SNI (Center), and SCE (Right) subjects. Maps demonstrate significantly increased regional heterogeneity of MTT measurements in SCE subjects as compared with NS and SNI subjects. Range: 0–8 seconds. (B) PBF normalized to the mean PBF for NS (Left), SNI (Center), and SCE (Right) subjects. As in MTT findings, there is increased regional heterogeneity in mean normalized PBF measurements in SCE subjects compared with NS and SNI subjects. The range on the color scale for MTT is 0-8 seconds and the range for mean normalized PBF is 25–175%.

Fig. 3.

MTT and PBF measurements (mean ± SEM) for dependent and nondependent regions of the lung. (A) Mean MTT did not differ between the nondependent and dependent regions for any of the groups. (B) In all three groups, mean normalized PBF measurements demonstrate increased flow in the dependent region and decreased flow in the nondependent region of the lung. (C) In all three groups the CV of MTT is increased in the nondependent region compared with the dependent region. (D) In all three groups the CV of mean normalized PBF is greater in the nondependent region than in the dependent region.