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Purpose  Vascular remodeling is a significant pathological feature of various pulmonary diseases, which may be assessed by quantitative computed tomography (CT) imaging. The purpose of this study was therefore to develop and validate an automatic method for quantifying pulmonary vascular morphology in CT images.    Methods  The proposed method consists of pulmonary vessel extraction and quantification. For extracting pulmonary vessels, a graph‐cuts‐based method is proposed which considers appearance (CT intensity) and shape (vesselness from a Hessian‐based filter) features, and incorporates distance to the airways into the cost function to prevent false detection of airway walls. For quantifying the extracted pulmonary vessels, a radius histogram is generated by counting the occurrence of vessel radii, calculated from a distance transform‐based method. Subsequently, two biomarkers, slope  α  and intercept  β , are calculated by linear regression on the radius histogram. A public data set from the VESSEL12 challenge was used to independently evaluate the vessel extraction. The quantitative analysis method was validated using images of a three‐dimensional (3D) printed vessel phantom, scanned by a clinical CT scanner and a micro‐CT scanner (to obtain a gold standard). To confirm the association between imaging biomarkers and pulmonary function, 77 scleroderma patients were investigated with the proposed method.    Results  In the independent evaluation with the public data set, our vessel segmentation method obtained an area under the receiver operating characteristic (ROC) curve of 0.976. The median radius difference between clinical and micro‐CT scans of a 3D printed vessel phantom was 0.062 ± 0.020 mm, with interquartile range of 0.199 ± 0.050 mm. In the studied patient group, a significant correlation between diffusion capacity for carbon monoxide and the biomarkers,  α  (R = −0.27,  P  = 0.018) and  β  (R = 0.321,  P  = 0.004), was obtained.    Conclusion  In conclusion, the proposed method was validated independently using a public data set resulting in an area under the ROC curve of 0.976 and using a 3D printed vessel phantom data set, showing a vessel sizing error of 0.062 mm (0.16 in‐plane pixel units). The correlation between imaging biomarkers and diffusion capacity in a clinical data set confirmed an association between lung structure and function. This quantification of pulmonary vascular morphology may be helpful in understanding the pathophysiology of pulmonary vascular diseases.

Automatic quantitative analysis of pulmonary vascular morphology in CT images