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      Review – 3D Micro CT Imaging of Renal Micro-Structural Changes

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          Abstract

          Appropriate nephron function is dependent on the detailed spatial interrelationship of blood vesselswith the tubular components. However, because of methodological limitations,the three-dimensional anatomical complexity of the renal vasculatureand its geometrical relationship with specific tubular segmentsalong the nephron has been difficult to study in a quantitativemanner. Three-dimensional microcomputed tomography (3D micro CT) offers the unique opportunity to image kidney sample volumes with a high spatial resolution (of up to 5 µm cubic voxel size) without physically sectioning them, thereby allowing accurate calculations of vessel tortuosity and density, as indices of neovascularization, as well as volume and distribution of various kidney structures. In conjunction with molecular biology techniques, valuable associations between renal microstructures and activation of local molecular pathways can be drawn to elucidate mechanisms of renal disease and design therapeutic approaches. For example, recent studies in animal models of renal hypertension, hypercholesterolemia, and diabetes mellitus have shown that medical intervention to decrease oxidative stress and micro-inflammation may preserve renal microstructures as well as renal function in these chronic renal diseases. Future developments will be needed to establish the place of 3D micro CT in developing, directing, and monitoring the treatment of chronic kidney diseases.

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          Most cited references 8

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          Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia.

          Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93+/-6%) and Group 2 (89+/-7%) but impaired in Group 3 (71+/-11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88+/-2.45 per-mm(2)) and Group 3 (4.50+/-1.37 per-mm(2)) compared to Group 1 (2.97+/-1.37 per-mm(2); P<0.05 vs. Group 2 and 3). This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.
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            Cortical microvascular remodeling in the stenotic kidney: role of increased oxidative stress.

            Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress. Three groups of pigs (n=6 each) were studied after 12 weeks of RAS, RAS+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (<500 microm) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1alpha, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RAS+antioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RAS+antioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1alpha mRNA expression. In contrast, expression of HIF-1alpha, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention. Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention.
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              Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries.

              In this study vasa vasorum in the walls of porcine coronary arteries were examined, using three-dimensional (3D) micro-CT scanning techniques. These techniques leave the 3D structure of the vasa vasorum tree intact and thus provide a much more direct view of this structure than is possible from conventional histological sections. The study demonstrates-for the first time, we believe-both the different types and the fine architecture of these vasa vasorum. Furthermore, with the use of automated tree analysis software, it was possible to obtain quantitative geometrical data on the 3D structure of vasa vasorum trees that have not previously been available. The results indicate that despite the restrictive topology of the space in which they are present, the branching architecture of the vasa vasorum trees, which we surveyed, is surprisingly similar to that of vasculature in general. The volume of vessel wall tissue perfused or drained by a vasa vasorum tree was found to correlate well with the cross-sectional area of the root segment of the vasa vasorum tree, and the luminal surface area corresponding to this volume was found to be comparable with the surface area of an early atherosclerotic lesion. This is consistent with earlier findings that the ligation or removal of vasa vasorum leads to atherogenesis.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                978-3-8055-8074-8
                978-3-318-01315-3
                1660-2110
                2006
                March 2006
                10 March 2006
                : 103
                : 2
                : c66-c70
                Affiliations
                Divisions of aCardiovascular Diseases and bNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minn., cDepartment of Biological Sciences, Minnesota State University, Mankato, Minn., USA
                Article
                90611 Nephron Clin Pract 2006;103:c66–c70
                10.1159/000090611
                16543758
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 16, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/90611
                Categories
                Radiologic Imaging

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