Intravascular and Extravascular Microvessel Formation in Chronic Total Occlusions : A Micro-CT Imaging Study

ObjectivesThe purpose of this study was to characterize the 3-dimensional structure of intravascular and extravascular microvessels during chronic total occlusion (CTO) maturation in a rabbit model.BackgroundIntravascular microchannels are an important component of a CTO and may predict guidewire crossability. However, temporal changes in the structure and geographic localization of these microvessels are poorly understood.MethodsA total of 39 occlusions were created in a rabbit femoral artery thrombin model. Animals were sacrificed at 2, 6, 12, and 24 weeks (n ≥8 occlusions per time point). The arteries were filled with a low viscosity radio-opaque polymer compound (Microfil) at 150 mm Hg pressure. Samples were scanned in a micro-computed tomography system to obtain high-resolution volumetric images. Analysis was performed in an image processing package that allowed for labeling of multiple materials.ResultsTwo distinct types of microvessels were observed: circumferentially oriented “extravascular” and longitudinally oriented “intravascular” microvessels. Extravascular microvessels were evident along the entire CTO length and maximal at the 2-week time point. There was a gradual and progressive reduction in extravascular microvessels over time, with very minimal microvessels evident beyond 12 weeks. In contrast, intravascular microvessel formation was delayed, with peak vascular volume at 6 weeks, followed by modest reductions at later time points. Intravascular microvessel formation was more prominent in the body compared with that in the proximal and distal ends of the CTO. Sharply angulated connections between the intravascular and extravascular microvessels were present at all time points, but most prominent at 6 weeks. At later time points, the individual intravascular microvessels became finer and more tortuous, although the continuity of these microvessels remained constant beyond 2 weeks.ConclusionsDifferences are present in the temporal and geographic patterns of intravascular and extravascular microvessel formation during CTO maturation.