Pulmonary vascular density: comparison of findings on computed tomography imaging with histology

Abstract

Background: Exposure to cigarette smoke has been shown to lead to vascular remodelling. Computed tomography (CT) imaging measures of vascular pruning have been associated with pulmonary vascular disease, an important morbidity associated with smoking. In this study we compare CT-based measures of distal vessel loss to histological vascular and parenchymal changes.

Methods: A retrospective review of 80 patients who had undergone lung resection identified patients with imaging appropriate for three-dimensional (3D) vascular reconstruction (n=18) and a second group for two-dimensional (2D) analysis (n=19). Measurements of the volume of the small vessels (3D) and the cross-sectional area of the small vessels (<5 mm² cross-section) were computed. Histological measures of cross-sectional area of the vasculature and loss of alveoli septa were obtained for all subjects.

Results: The 2D cross-sectional area of the vasculature on CT imaging was associated with the histological vascular cross-sectional area (r=0.69; p=0.001). The arterial small vessel volume assessed by CT correlated with the histological vascular cross-sectional area (r=0.50; p=0.04), a relationship that persisted even when adjusted for CT-derived measures of emphysema in a regression model.

Conclusions: Loss of small vessel volume in CT imaging of smokers is associated with histological loss of vascular cross-sectional area. Imaging-based quantification of pulmonary vasculature provides a noninvasive method to study the multiscale effects of smoking on the pulmonary circulation.

Figure 1.

Photograph of a section prepared from excised lung tissue of patients undergoing lung resection for a tumor (A). Vessels were identified manually and colored in. The cross sectional area of vessels less than 500μ were added and divided by the entire field of view to derive the Histologic Vessel Cross Sectional Area (%hist-VCSA)(B). To measure the proportion of tissue structures, a grid point was placed and points corresponding to alveolar septa, vessels and bronchiole were identified(C). The thickness of the wall, wall components and lumen were measured from individual arteries (D). Example artery from a nonsmoker (left panel in D), one from a subject with GOLD II COPD (middle panel in D) and one from GOLD III disease (right panel in D) are shown here.

Figure 2.

Examples of 3D vascular reconstruction in two subjects both with GOLD II COPD. Imaging of the subject to the left shows proximal dilation and loss of distal vasculature as compared to the subject on the right. The color indicates the radius of the vessel with red coloring representing smaller vessels. On histology, the subject on the left has a lower %hist-VCSA (6.3 versus 8.6). (VCSA: Vascular cross-sectional area)

Figure 3.

Summary of results from the 2D analysis showing a correlation between cross-sectional area of vessels of less than 5mm² assessed by CT scan and histologic metrics of small vessel (diameter <500 μm) density (%hist-VCSA) as well as the estimated proportion of alveolar septa. (VCSA: Vascular Cross Sectional Area).

Figure 4.

Example of 3D reconstruction of a right lung (A) where blue indicates larger (radius of 6mm and cross sectional area of ^~110mm²) and red indicates smaller vessels with radius of 0.5mm and cross sectional area of 0.8mm² (B) shows the subsequent automated arterial and venous segmentation where blue denotes arteries and red denotes veins.

Figure 5.

Relationship between estimated vascular volume in arterial BV5 and venous BV5 small vessels normalized by lung volume or by tissue volume and histologic metrics of small vessel (diameter <500 μm) density (%hist-VCSA) and the estimated proportion of alveolar septa. Correlation coefficients are nonparametric (Spearman). (BV5: blood vessel volume in vessels less than 5mm² in cross sectional area; VCSA: vascular cross sectional area; NELV: non-emphysematous lung volume)