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Adventitial vasa vasorum in balloon-injured coronary arteries

Visualization and quantitation by a microscopic three-dimensional computed tomography technique

Hyuck Moon Kwon, MD^a, Giuseppe Sangiorgi, MD^a, Erik L. Ritman, MD, PhD^*, Amir Lerman, MD^a, Charles McKenna, MD^a, Renu Virmani, MD, William D. Edwards, MD, David R. Holmes, MD^a and Robert S. Schwartz, MD^a

^a Department of Internal Medicine and Cardiovascular Diseases, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
^* Department of Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
Division of Medical Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
Department of Cardiovascular Pathology, Armed Force Institute of Pathology, Washington, DC, USA

View larger version (40K): [in a new window]   Figure 1 Schematic drawing of micro-CT reconstructed coronary artery cross-section. The vessel wall area was defined as a radius twice the distance from the arterial lumen to the outer adventitia. See text for details.

View larger version (115K): [in a new window]   Figure 2 Voxel gradient shading of normal coronary artery shown at two different angles on the sagittal plane (voxel size, 28 µm). Two anatomically different type of vasa vasorum are visualized. First-order vasa (arrow) originate from the main lumen of the coronary artery (arrow) running longitudinally along the adventitial surface of the artery. Second-order vasa (triangle) originate directly from the first-order vasa, and form a plexus circumferentially around the vessel wall, as arch arterioles.

View larger version (100K): [in a new window]   Figure 3 Maximum intensity projection and voxel gradient shading from a normal pig coronary artery demonstrated different origination and spatial distribution of vasa vasorum (voxel size, 28 µm). First-order vasa vasorum are indicated by white arrows. Second-order vasa vasorum are indicated by black triangles. A coronary vein is also visualized (asterisk).

View larger version (75K): [in a new window]   Figure 4 Maximum intensity projection and voxel gradient shading from a porcine coronary artery 28 d after balloon injury (voxel size, 28 µm). In the outer region of the vessel wall, in correspondence with the site of lumen stenosis due to neointimal hyperplasia, a dense plexus of newly formed vasa vasorum is present. First-order vasa vasorum are indicated by white arrows. Second-order vasa vasorum are indicated by black triangles.

View larger version (75K): [in a new window]   Figure 5 High-resolution micro-CT cross-sectional images from normal (A) and balloon-injured (B) porcine coronary arteries (voxel size, 21 µm). Vasa vasorum are present in the outer region of the vessel wall. Note the thickened vessel wall and significant angiogenesis 28 d after balloon injury. A distinct lower x-ray density within the main lumen indicates neointimal tissue. No neovascularization is present in the neointima itself. First-order vasa vasorum are indicated by arrows and second-order vasa vasorum by triangle.

View larger version (19K): [in a new window]   Figure 6 A, Vasa vasorum density between normal and balloon-injured coronary arteries. A significant increase in the density of vasa vasorum is present 28 d after balloon injury. B, Density ratio of first- (open bars) and second-order vasa vasorum (hatched bars) between normal and balloon-injured coronary arteries. Twenty-eight days after PTCA there was a shift in the ratio of first- to second-order vasa vasorum.

View larger version (16K): [in a new window]   Figure 7 A, Linear regression analysis between percentage lumen stenosis and density of vasa vasorum in porcine coronary arteries after PTCA (n = 32, r = 0.81, p < 0.0001). B, Percentage lumen stenosis and the corresponding density of vasa vasorum along the entire length of a single coronary segment. In this example, as the stenosis severity increased, so did the vasa vasorum density (r = 0.88, p = 0.0001).

View larger version (14K): [in a new window]   Figure 8 Linear regression analysis between cross-sectional total number vasa vasorum evaluated by micro-CT and total number vasa vasorum evaluated by histologic analysis. A significant correlation is present, indicating a good correspondence between the two techniques.