Quantitation and Visualization of Vasa Vasorum and Neointimal Development in Three Dimensions—High-resolution Microscopic Computed Tomography Analysis
Daniel J Pelchovitz University of Pennsylvania Cardiovascular Division, Hospital of the University of Pennsylvania , Robert L Wilensky University of Pennsylvania Cardiovascular Division, Hospital of the University of Pennsylvania
We have used three-dimensional micro-CT to quantify the density of vasa vasorum in swine coronary arteries treated with drug-eluting stents. Using micro-CT, the density and number of vasa vasorum were compared in stented and unstented sections of the artery. There were, however, some problems with using micro-CT in the imaging of stented arteries. Owing to the metallic nature of the stents, there is image artifact that has similar density to the contrast material used to fill arterial beds. For this reason, it is necessary to use region-growing, a computerized technique that requires manual selection of vasa vasora and maps regions with similar densities. Vasa vasora are thus assigned a density value greater than that of the stent artifact. Using MicroView software, the number of pixels with this assigned high-density value are quantified and compared with the number of pixels without the highdensity value to give a density measurement of the vasa vasorum. This allows for the exclusion of artifact from density calculations. With experience, this technique allows for accurate and efficient quantification of the vasa.
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Analysis of static measurements such as quantitation of the vasa are optimal for conventional micro-CT, but some physiological processes are too transient to be analyzed by this modality as the production of an image with an acceptable signal/noise ratio may take several hours. Cryostatic micro-CT, a technique that utilizes ‘snap-freezing’ of specimens before the scanning process, has evolved to remedy this situation.18,19 Using this technique, the time-course of solute transfer from the arterial lumen and adventitial vasa vasorum was elucidated, based on arteries snap-frozen at small intervals of time.19 Micro-CT is also a highly accurate form of imaging in the evaluation of intravascular stent position. Owing to the three-dimensional nature of the imaging and the high resolution, it is possible to accurately determine the position of the stent against the arterial wall in intact arteries, avoiding the inherent imprecision and cutting artifact of cross-sectional analysis by histology. Additionally, the high resolution of the imaging allows for analysis of neointimal proliferation (see Figure 1). Using analysis software, it is possible to accurately quantify the amount of neointima in three dimensions in intact stented arteries. This accurate quantification of neointimal hyperplasia has broad applications in experimental studies of novel stents. In addition to the use of micro-CT for the analysis of the arterial vasa vasorum and stent geometry, the three-dimensional nature of the images generated has found use in analysis of other aspects of arterial anatomy and pathophysiology. Micro-CT has been used to quantify and analyze threedimensional calcification patterns in coronary arteries with atherosclerotic plaques.20 Micro-CT studies are likely to become increasingly important to visualize spatial patterns in the media and adventitia of diseased arteries that have been subjected to various medications and stents to identify devices or agents that might decrease development of atherosclerosis and in-stent restenosis.