A New Conversation between Radiology and Pathology-Identifying Microvascular Architecture in Stages of Cirrhosis via Diffraction Enhanced Imaging In Vitro

Abstract

Background/AimDiffraction enhanced imaging (DEI) is a synchrotron radiation X-ray phase-contrast imaging technique that can better reveal the microstructure of biological soft tissues than conventional X-rays. The aim of this study is to investigate the angio-architectural changes of the liver during fibrosis, cirrhosis and its subsequent regression by applying synchrotron radiation based DEI.MethodsDEI experiments were performed at the 4W1A station of Beijing Synchrotron Radiation Facility. Twenty-four Sprague-Dawley rats were induced with liver fibrosis by carbon tetrachloride (CCl4) for up to 10 weeks, after which spontaneous regression started and continued until week 30. Quantitative analysis of the DEI images yielded the mean vascular density and intercapillary distance, which was then re-confirmed by immunohistochemical analysis of CD34.ResultsBased on the DEI results, the mean vascular density was 1.4-fold higher in fibrotic rats (at week 6) and 2-fold higher in cirrhotic rats (at week 10) compared with the control (p<0.05). Accordingly, the intercapillary distance decreased to 563.89±243.35 µm in fibrotic rats and 392.90±92.68 µm in cirrhotic rats compared with 673.85±214.16µm in the control (p<0.05). During fibrosis regression at week 30, vascular density was 0.7-fold lower and intercapillary distance increased to 548.60±210.94 µm as compared with cirrhotic rats (p<0.05).In parallel to the DEI results, immunohistochemical analysis of CD34 showed similar changes.ConclusionSynchrotron-based DEI can conduct radiological as well as pathological analysis. Our results are consistent with previous reports indicating that angiogenesis is directly proportional to fibrosis progression. Furthermore, by clarifying the vascular characteristics of liver diseases, DEI reveals that cirrhosis cannot fully reverse during fibrosis regression.

Three-dimensional visualization of the microvasculature of bile duct ligation-induced liver fibrosis in rats by x-ray phase-contrast imaging computed tomography

“…By means of PCI technique, a study of liver fibrosis imaging has been developed by the investigators; however, these studies were performed in two dimensions and suffered from the overlapping of structures 4 5 6 . Our previous study has demonstrated that PCI-CT can present an accurate 3D morphology of the microvasculature based on liver fibrosis model in rats induced by human albumin and can characterize different stages of fibrosis progression based on high-resolution 3D vessel images 7 .…”

“…Ultimately, liver fibrosis may lead to cirrhosis and reduce liver functional reserve 2 3 . The development and variation of liver fibrosis always correlates with changes in microvascular structure and morphology 4 5 6 7 . The microvascular changes are regarded as one of the most important and recently discovered pathophysiological features of liver fibrosis 8 9 .…”

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

“…However, the spatial resolution of in vivo μCT scans is limited to 35 μm voxel edge length [6]. With the use of synchrotron radiation-based microtomography (SRμCT), by providing a high photon flux and phase-sensitive imaging protocols, spatial resolutions of 10.9 to 3.5 μm isometric voxel sizes were reached in the assessment of liver fibrosis [12][13][14][15][16][17]. While a detailed depiction and characterization of macrovessels and smaller intrahepatic arterioles and venules was achieved, the sinusoidal vascular bed remained beyond the spatial resolution capacities in previous studies.…”

Acoustic Radiation Force Impulse (ARFI) Elastography and Serological Markers in Assessment of Liver Fibrosis and Free Portal Pressure in Patients with Hepatitis B

“…In the initial stage, the process is manifested as extrahepatocellular deposition of fibrous matrix, which may progress to cause structural changes and reconstruction of hepatic lobules and ultimately lead to cirrhosis [ 1 ]. Researchers have found that the degree of LF can reflect the effectiveness of antiviral therapy in patients with viral liver diseases, where the severity of LF is associated with patients’ clinical outcomes and may reflect the prognosis of patients [ 2 , 3 ]. LF can be caused by a variety of factors such as viral infection, alcohol abuse, and autoimmune diseases, which may ultimately progress to cirrhosis.…”