3D analysis of microvasculature in murine liver fibrosis models using synchrotron radiation-based microtomography

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.

Use of the volume-averaged Murray’s deviation method for the characterization of branching geometry in liver fibrosis: a preliminary study on vascular circulation

“…Liver fibrosis is a dynamic process characterized by increased collagen content and altered vascular structures. In recent years, vascular alterations have attracted much attention (37,38). PCCT, which has undergone rapid progress over the last 20 years, provides high spatial resolution and excellent soft-tissue contrast in imaging biological samples, making it possible to perform both 3D visualization and quantitative analysis of the vascular alterations in liver fibrosis (9,39).…”

Auf dem Weg zum virtuellen Mikroskop: Synchrotron-basierte dreidimensionale Bildgebung in der Pathologie

“…Hierbei wurde bei verschiedenen tierexperimentellen Modellen von Leberfibrosen der zeitliche Verlauf von Gefäßveränderungen (Abb. 5 ) in Korrelation zu der Fibrosierung aufgezeigt [ 19 ] oder auch der therapeutische Effekt neuer Wirkstoffe bei Bleomycin-induzierten Lungenfibrosen [ 20 ]. Über morphometrische Algorithmen lassen sich somit Gefäßdichten- und -volumina, Verzweigungswinkel, Fibrosedichte oder auch Tumor- und Nekrosevolumina relativ einfach bestimmen.…”