Purpose:To establish high-resolution magnetic resonance angiography (MRA) protocols to monitor and quantify dynamic changes of vascular remodeling in pathologic mouse models. Materials and Methods:Time-of-flight (TOF) MRA of murine vessels was performed at 9.4T to monitor temporal alterations in the vessel structure in two frequently used injury models (wire denudation of carotid artery and femoral artery occlusion). Quantification of vessel morphology was performed with the use of in-house-developed software and validated by estimation of inter-and intraobserver variabilities and reproducibility, and by correlation with histological data. Results:MRA-based volume determination exhibited low intra-and interobserver variabilities and high reproducibility. Furthermore, good correlations with histological data were found four weeks after injury (R 2 ϭ 0.970). Two highresolution image series are presented to demonstrate the applicability of the technique: 1) the time course of a vessel stenosis that reopens by thrombus recanalization, and 2) the continuous restoration of blood flow by collateral vessel formation during arteriogenesis after induction of hindlimb ischemia. Conclusion:We describe high-resolution MRA imaging protocols that are suitable for sensitively measuring the extent and time course of changes in vessel morphology in mice in a repetitive manner without any contrast agent. This methodology provides a reliable tool for noninvasive monitoring of vascular lesion development or neovascularization in transgenic mice. GENETICALLY MODIFIED MICE HAVE BEEN well established as models for studying dynamic processes in vascular biology, such as the development of vessel stenosis or the initiation of neovascularization. For this purpose, generated mutants are frequently subjected to experimental models, such as wire-induced denudation of the common carotid artery (CCA) (1,2) and ligation of the femoral artery (hindlimb ischemia) (3,4), respectively. In general, these models are evaluated by ex vivo histopathology, which provides information at the time of harvest only. Furthermore, this technique is partially tissue-destructive, only a limited region of the vessel is accessible to histology, and the analysis of luminal area and stenosis is complicated by fixation artifacts. Consequently, noninvasive, repetitive three-dimensional monitoring would be highly desirable for continuous, quantitative vessel analysis.All previous MR-based approaches to study the formation of collateral vessels after hindlimb ischemia were, to our knowledge, restricted to a qualitative threedimensional assessment of newly developed flow (5,6) or to quantitative analysis of two-dimensional gradient echo images (6 -9). Similarly, a two-dimensional MRI method was used to monitor alterations in vessel morphology after wire denudation of the CCA by Manka et al (10). However, the reported method requires relatively long sampling times (about 40 minutes) as well as complex analysis procedures. Nevertheless, the MR data could be satisfactorily c...

Serial assessment of dynamic changes of vessel growth and metabolism in the process of arteriogenesis demonstrate that the lack of CD73-derived adenosine importantly promotes arteriogenesis but does not alter angiogenesis in our model of hindlimb ischaemia.

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