Abstract
BackgroundAnimal models of focal cerebral ischemia are widely used in stroke research. The purpose of our study was to evaluate and compare the cerebral macro- and microvascular architecture of rats in two different models of permanent middle cerebral artery occlusion using an innovative quantitative micro- and nano-CT imaging technique.Methods4h of middle cerebral artery occlusion was performed in rats using the macrosphere method or the suture technique. After contrast perfusion, brains were isolated and scanned en-bloc using micro-CT (8 μm)3 or nano-CT at 500 nm3 voxel size to generate 3D images of the cerebral vasculature. The arterial vascular volume fraction and gray scale attenuation was determined and the significance of differences in measurements was tested with analysis of variance [ANOVA].ResultsMicro-CT provided quantitative information on vascular morphology. Micro- and nano-CT proved to visualize and differentiate vascular occlusion territories performed in both models of cerebral ischemia. The suture technique leads to a remarkable decrease in the intravascular volume fraction of the middle cerebral artery perfusion territory. Blocking the medial cerebral artery with macrospheres, the vascular volume fraction of the involved hemisphere decreased significantly (p < 0.001), independently of the number of macrospheres, and was comparable to the suture method. We established gray scale measurements by which focal cerebral ischemia could be radiographically categorized (p < 0.001). Nano-CT imaging demonstrates collateral perfusion related to different occluded vessel territories after macrosphere perfusion.ConclusionMicro- and Nano-CT imaging is feasible for analysis and differentiation of different models of focal cerebral ischemia in rats.
Highlights
Animal models of focal cerebral ischemia are widely used in stroke research
Over the last decade, the rat has become the predominant species for models of focal cerebral ischemia
A monofilament is implemented into the internal carotid artery (ICA) until it blocks blood flow to the middle cere
Summary
Animal models of focal cerebral ischemia are widely used in stroke research. The purpose of our study was to evaluate and compare the cerebral macro- and microvascular architecture of rats in two different models of permanent middle cerebral artery occlusion using an innovative quantitative micro- and nano-CT imaging technique. Among the endovascular techniques for middle cerebral artery occlusion (MCAO), the suture occlusion technique in rats is the most frequently used method [1,2,3] In this model, a monofilament is implemented into the internal carotid artery (ICA) until it blocks blood flow to the middle cere-. The recently introduced macrosphere model has been developed to overcome these side effects by the intraarterial embolization of TiO2 spheres which selectively block blood flow to the MCA main stem without obstructing the hypothalamic artery [4,6]. Detailed anatomical data about the vascular status, are generally sparse because (i) of the difficulty in their quantification, (ii) of difficulty to demonstrate their interconnectivity to other vessels (collaterals), (iii) of their very fine anatomy in animal models of focal cerebral ischemia
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