Abstract
BackgroundThe angiogenesis of liver cancer is a key condition for its growth, invasion, and metastasis. This study aims to investigate vascular network connectivity of hepatocellular carcinoma (HCC) using graph-based approach.MethodsOrthotopic HCC xenograft models (n=10) and the healthy controls (n=10) were established. After 21 days of modeling, hepatic vascular casting and Micro-CT scanning were performed for angiography, followed by blood vessels automatic segmentation and vascular network modeling. The topologic parameters of vascular network, including clustering coefficient (CC), network structure entropy (NSE), and average path length (APL) were quantified. Topologic parameters of the tumor region, as well as the background liver were compared between HCC group and normal control group.ResultsCompared with normal control group, the tumor region of HCC group showed significantly decreased CC [(0.046 ± 0.005) vs. (0.052 ± 0.006), P=0.026], and NSE [(0.9894 ± 0.0015) vs. (0.9927 ± 0.0010), P<0.001], and increased APL [(0.433 ± 0.138) vs. (0.188 ± 0.049), P<0.001]. Compared with normal control group, the background liver of HCC group showed significantly decreased CC [(0.047 ± 0.004) vs. (0.052 ± 0.006), P=0.041] and increased NSE [0.9938 (0.9936~0.9940) vs. (0.9927 ± 0.0010), P=0.035]. No significant difference was identified for APL between the two groups.ConclusionGraph-based approach allows quantification of vascular connectivity of HCC. Disrupted vascular topological connectivity exists in the tumor region, as well as the background liver of HCC.
Highlights
Disrupted vascular topological connectivity exists in the tumor region, as well as the background liver of Hepatocellular carcinoma (HCC)
Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by neoangiogenesis, which contributes to the high rate of metastasis and dismal prognosis [1]
Our study demonstrates the feasibility to investigate vascular topological connectivity of HCC using graph analysis based on micro-CT, we tends to show abnormal vascular connectivity compared to normal liver
Summary
Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by neoangiogenesis, which contributes to the high rate of metastasis and dismal prognosis [1]. Immunochemistrical microvessel density (MVD) is still the most accepted and applied index for the measurement of HCC vascularization, in which high tumor neovascularization often represents high invasiveness. MVD measurement is limited by its invasive nature, determination of hotspot, counting methods, and the inability to fully capture the vascular trajectory and tissue complexity in the entire tumor [4, 5]. The main drainage vessels of hepatocellular nodules change from hepatic veins to hepatic sinusoids, and to portal veins during hepatocarcinogenesis [7]. This study aims to investigate vascular network connectivity of hepatocellular carcinoma (HCC) using graph-based approach
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