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

Sara K Alford; Edwin J. R van Beek; Geoffrey McLennan; Eric A Hoffman

doi:10.1073/pnas.0913880107

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

Journal article

Open access

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

Sara K Alford, Edwin J. R van Beek, Geoffrey McLennan and Eric A Hoffman

Proceedings of the National Academy of Sciences - PNAS, Vol.107(16), pp.7485-7490

04/20/2010

DOI: 10.1073/pnas.0913880107

PMCID: PMC2867701

PMID: 20368443

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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.

computed tomography

Biological Sciences

hypoxic pulmonary vasoconstriction

pulmonary circulation

pulmonary emphysema

chronic obstructive pulmonary disease

Details

Title: Subtitle: Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers
Creators: Sara K Alford - Departments of
Edwin J. R van Beek - Departments of
Geoffrey McLennan - Departments of
Eric A Hoffman - Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(16), pp.7485-7490
DOI: 10.1073/pnas.0913880107
PMID: 20368443
PMCID: PMC2867701
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 04/20/2010
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984051525802771

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