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Abstract-We investigated whether circulating endothelial progenitor cells contribute to neovascularization after stroke.Donor bone marrow cells obtained from transgenic mice constitutively expressing ␤-galactosidase transcriptionally regulated by an endothelial-specific promoter, Tie2, were injected into adult mice. Focal cerebral ischemia was induced by embolic middle cerebral artery (MCA) occlusion and changes of cerebral blood flow (CBF) were measured by perfusion-weighted magnetic resonance imaging (MRI). Laser scanning confocal microscopy (LSCM), immunohistochemistry and X-gal staining were performed. Perfusion-weighted MRI demonstrated increases in CBF around the boundary of an infarct area 1 month after ischemia. Morphological and 3-dimensional image analyses revealed enlarged and thin-walled blood vessels with sprouting or intussusception at the boundary of the ischemic lesion, which closely corresponded to elevated CBF areas detected on perfusion-weighted MRI, indicating the presence of neovascularization. X-gal and double immunostaining demonstrated that Tie2-lacZ-positive cells incorporated into sites of neovascularization at the border of the infarct, and these cells exhibited an endothelial antigenic marker (von Willebrand factor). In addition, bone marrow recipient mice without ischemia showed incorporation of Tie2-lacZ-expressing cells into vessels of the choroid plexus. These data suggest that formation of new blood vessels in the adult brain after stroke is not restricted to angiogenesis but also involves vasculogenesis and that circulating endothelial progenitor cells from bone marrow contribute to the vascular substructure of the choroid plexus. Key Words: bone marrow Ⅲ endothelial progenitor cells Ⅲ neovascularization Ⅲ cerebral ischemia Ⅲ Tie2 I n the early embryogenesis, the vascular system develops from vasculogenesis in which angioblasts differentiate into endothelial cells to form a primitive capillary network, whereas angiogenesis, the sprouting of capillaries from preexisting blood vessels, is involved in the late stage of embryogenesis and in the adult. 1 Angioblast-like circulating endothelial progenitor cells are present in the peripheral blood and have been isolated from adult animals. 2,3 Injection of circulating endothelial progenitor cells into animals with hindlimb or myocardial ischemia results in incorporation of circulating endothelial progenitor cells into neovasculature at the site of ischemia, suggesting that circulating endothelial progenitor cells contribute to formation of new blood vessels in the adult tissue. 4 The endothelial cells of cerebral capillaries differ functionally and morphologically from those of noncerebral capillaries. 5,6 During embryonic development, the cerebral vascular system originates from the perineural plexus when vascular sprouts invade the proliferating neuroectoderm, indicating that the cerebral vascular system is primarily developed by angiogenesis and not by vasculogenesis. 7 The cerebral endothelial cells are linked by complex tight junc...

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Magnetic susceptibility is an important physical property of tissues, and can be used as a contrast mechanism in magnetic resonance imaging. Recently, targeting contrast agents by conjugation with signaling molecules and labeling stem cells with contrast agents have become feasible. These contrast agents are strongly paramagnetic, and the ability to quantify magnetic susceptibility could allow accurate measurement of signaling and cell localization. Presented here is a technique to estimate arbitrary magnetic susceptibility distributions by solving an ill-posed inversion problem from field maps obtained in an MRI scanner. Two regularization strategies are considered, conventional Tikhonov regularization, and a sparsity promoting nonlinear regularization using the ℓ1 norm. Proof of concept is demonstrated using numerical simulations, phantoms, and in a stroke model mouse. Initial experience indicates that the nonlinear regularization better suppresses noise and streaking artifacts common in susceptibility estimation.

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