3D analysis of microvasculature in murine liver fibrosis models using synchrotron radiation-based microtomography
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SHORT COMMUNICATION
3D analysis of microvasculature in murine liver fibrosis models using synchrotron radiation‑based microtomography Willi L. Wagner1,2 · Sonja Föhst3 · Jessica Hock4 · Yong Ook Kim5 · Yury Popov6 · Detlef Schuppan5,6 · Katja Schladitz7 · Claudia Redenbach3 · Maximilian Ackermann4,8 Received: 22 June 2020 / Accepted: 28 September 2020 © The Author(s) 2020
Abstract Cirrhosis describes the development of excess fibrous tissue around regenerative nodules in response to chronic liver injury and usually leads to irreversible organ damage and end-stage liver disease. During the development of cirrhosis, the formation of collagenous scar tissue is paralleled by a reorganization and remodeling of the hepatic vascular system. To date, macrovascular remodeling in various cirrhosis models has been examined using three-dimensional (3D) imaging modalities, while microvascular changes have been studied mainly by two-dimensional (2D) light microscopic and electron microscopic imaging. Here, we report on the application of high-resolution 3D synchrotron radiation-based microtomography (SRμCT) for the study of the sinusoidal and capillary blood vessel system in three murine models of advanced parenchymal and biliary hepatic fibrosis. SRμCT facilitates the characterization of microvascular architecture and identifies features of intussusceptive angiogenesis in progressive liver fibrosis in a non-destructive 3D manner. Keywords Cirrhosis · Angiogenesis · Intussusceptive angiogenesis · Image analysis · Synchrotron radiation microcomputed tomography
Introduction Cirrhosis is caused by an excess deposition of collagenous connective tissue in an abnormal wound healing response to continuous liver injury [1–3]. In the process of ongoing fibrogenesis and increasing fibrosis, the vascular system is adversely reorganized to affect the hepatic circulation on the macroscopic and the microscopic scale, leading to severe Willi L. Wagner and Sonja Föhst have contributed equally and share first authorship. * Maximilian Ackermann maximilian.ackermann@uni‑mainz.de 1
Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
2
Translational Lung Research Center, Member of the German Center for Lung Research, University of Heidelberg, Heidelberg, Germany
3
Mathematics Department, Technische Universität Kaiserslautern, Kaiserslautern, Germany
4
Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Johann‑Joachim‑Becher‑Weg 13, 55128 Mainz, Germany
clinical complications such as portal hypertension and functional liver failure. On the micron scale, sharp bends, abnormal branching, and an increased tortuosity of vessels were observed by deep tissue microscopy (DTM) [4]. These microvascular alterations likely cause an aggravation of portal hypertension during hepatic fibrosis [5]. On the micron level, fibrotic liver tissue and the sinusoidal vascular system are conventionally investigated by light microscopy of his
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