Cardiac micro-computed tomography imaging of the aging coronary vasculature

Abstract

Background: Alterations at the level of the coronary circulation with aging may play an important role in the evolution of age-associated changes in left ventricular (LV) fibrosis and function. However these age-associated changes in the coronary vasculature remain poorly defined primarily due to the lack of high resolution imaging technologies. The current study was designed to utilize cardiac micro-computed tomography (micro-CT) technology as a novel imaging strategy, to define the 3-dimensional coronary circulation in the young and aged heart and its relationship to LV fibrosis and function.

Methods and results: Young (2 months old; n=10) and aged (20 months old; n=10) Fischer rats underwent cardiac micro-CT imaging as well as echocardiography, blood pressure, and fibrosis analysis. Importantly, when indexed to LV mass, which increased with age, the total and intramyocardial vessel volumes were lower, whereas the epicardial vessel volume, with and without indexing to LV mass, was significantly higher in the aged hearts compared with the young hearts. Moreover, the aged hearts had a significantly lower percentage of intramyocardial vessel volume and a significantly higher percentage of epicardial vessel volume, when normalized to the total vessel volume, compared with the young hearts. Further, the aged hearts had significant LV fibrosis and mild LV dysfunction compared with the young hearts.

Conclusions: This micro-CT imaging study reports the reduction in normalized intramyocardial vessel volume within the aged heart, in association with increased epicardial vessel volume, in the setting of increased LV fibrosis, and mild LV dysfunction.

Figure 1

A representative 3-D maximum intensity micro-CT projection image of the young (A) and aged (B) Fischer heart with Microfil contrast agent injected into the coronary arteries. Figures 1C and 1D are representative computer generated renderings of the opacified lumens of the coronary vessels in a young (C) and aged (D) Fischer rat heart. The epicardial vessels are displayed in red and the intramyocardial vessels are displayed in blue.

Figure 1

A representative 3-D maximum intensity micro-CT projection image of the young (A) and aged (B) Fischer heart with Microfil contrast agent injected into the coronary arteries. Figures 1C and 1D are representative computer generated renderings of the opacified lumens of the coronary vessels in a young (C) and aged (D) Fischer rat heart. The epicardial vessels are displayed in red and the intramyocardial vessels are displayed in blue.

Figure 2

Graph illustrating the quantitative assessment of the percent vessel volume by diameter normalized to total vessel volume in young and aged hearts. As the voxel size was 20 μm, the diameter vessel range is in 40 μm increments for each point on the graph. Values are mean ± SE. n=5 for both age groups. *P<0.05 at the specific vessel luminal diameter.

Figure 3

Graphs illustrating the mean percent values of intramyocardial vessel volume (A) and epicardial vessel volume (B) normalized to total vessel volume. Values are mean ± SE. n=5 for both age groups. *P<0.05.

Figure 4

Representative histological myocardial image at 40x objective magnification (A) and quantification of picrosirius red staining (B) of LV fibrosis between young and aged hearts. Values are mean ± SE. n=5 for both age groups. *P<0.05.