Assessment of Vascular Network Connectivity of Hepatocellular Carcinoma Using Graph-Based Approach

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Jul 23

PMID 34295812

Authors

Qiaoyu Liu

Boyu Zhang

Luna Wang

Rencheng Zheng

Jinwei Qiang

He Wang

Fuhua Yan

Ruokun Li

Affiliations

Soon will be listed here.

Abstract

Background: The 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.

Methods: Orthotopic 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.

Results: Compared with normal control group, the tumor region of HCC group showed significantly decreased CC [(0.046 ± 0.005) (0.052 ± 0.006), =0.026], and NSE [(0.9894 ± 0.0015) (0.9927 ± 0.0010), <0.001], and increased APL [(0.433 ± 0.138) (0.188 ± 0.049), <0.001]. Compared with normal control group, the background liver of HCC group showed significantly decreased CC [(0.047 ± 0.004) (0.052 ± 0.006), =0.041] and increased NSE [0.9938 (0.9936~0.9940) (0.9927 ± 0.0010), =0.035]. No significant difference was identified for APL between the two groups.

Conclusion: Graph-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.

References

Chen Z, Wei W, Guo Z, Lin J, Shi M, Guo R . Morphologic classification of microvessels in hepatocellular carcinoma is associated with the prognosis after resection. J Gastroenterol Hepatol. 2011; 26(5):866-74. DOI: 10.1111/j.1440-1746.2010.06511.x. View

Sharma S, Sharma M, Sarkar C . Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis. Histopathology. 2005; 46(5):481-9. DOI: 10.1111/j.1365-2559.2005.02142.x. View

Peeters G, Debbaut C, Friebel A, Cornillie P, De Vos W, Favere K . Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat. J Anat. 2017; 232(3):485-496. PMC: 5807949. DOI: 10.1111/joa.12760. View

Peeters G, Debbaut C, Laleman W, Monbaliu D, Vander Elst I, Detrez J . A multilevel framework to reconstruct anatomical 3D models of the hepatic vasculature in rat livers. J Anat. 2016; 230(3):471-483. PMC: 5314389. DOI: 10.1111/joa.12567. View

Zou T, She L, Zhan C, Gao Y, Chen H . Altered Topological Properties of Gray Matter Structural Covariance Networks in Minimal Hepatic Encephalopathy. Front Neuroanat. 2018; 12:101. PMC: 6281039. DOI: 10.3389/fnana.2018.00101. View

Rubinov M, Sporns O . Complex network measures of brain connectivity: uses and interpretations. Neuroimage. 2009; 52(3):1059-69. DOI: 10.1016/j.neuroimage.2009.10.003. View

Amat-Roldan I, Berzigotti A, Gilabert R, Bosch J . Assessment of Hepatic Vascular Network Connectivity with Automated Graph Analysis of Dynamic Contrast-enhanced US to Evaluate Portal Hypertension in Patients with Cirrhosis: A Pilot Study. Radiology. 2015; 277(1):268-76. DOI: 10.1148/radiol.2015141941. View

Heimbach J, Kulik L, Finn R, Sirlin C, Abecassis M, Roberts L . AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2017; 67(1):358-380. DOI: 10.1002/hep.29086. View

Renne S, Woo H, Allegra S, Rudini N, Yano H, Donadon M . Vessels Encapsulating Tumor Clusters (VETC) Is a Powerful Predictor of Aggressive Hepatocellular Carcinoma. Hepatology. 2019; 71(1):183-195. DOI: 10.1002/hep.30814. View

10.

Lin X, Chen Y, Wang M, Song C, Lin B, Yuan X . Altered Topological Patterns of Gray Matter Networks in Tinnitus: A Graph-Theoretical-Based Study. Front Neurosci. 2020; 14:541. PMC: 7267018. DOI: 10.3389/fnins.2020.00541. View

11.

Pabst A, Ackermann M, Wagner W, Haberthur D, Ziebart T, Konerding M . Imaging angiogenesis: perspectives and opportunities in tumour research - a method display. J Craniomaxillofac Surg. 2014; 42(6):915-23. DOI: 10.1016/j.jcms.2014.01.010. View

12.

Ehling J, Theek B, Gremse F, Baetke S, Mockel D, Maynard J . Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization. Am J Pathol. 2013; 184(2):431-41. PMC: 3920056. DOI: 10.1016/j.ajpath.2013.10.014. View

13.

Peeters G, Debbaut C, Cornillie P, De Schryver T, Monbaliu D, Laleman W . A multilevel modeling framework to study hepatic perfusion characteristics in case of liver cirrhosis. J Biomech Eng. 2014; 137(5):051007. DOI: 10.1115/1.4029280. View

14.

Ronellenfitsch H, Katifori E . Global Optimization, Local Adaptation, and the Role of Growth in Distribution Networks. Phys Rev Lett. 2016; 117(13):138301. DOI: 10.1103/PhysRevLett.117.138301. View

15.

Phillips M, Moore S, Shah M, Lee C, Lee Y, Faber J . A method for evaluating the murine pulmonary vasculature using micro-computed tomography. J Surg Res. 2016; 207:115-122. PMC: 5898376. DOI: 10.1016/j.jss.2016.08.074. View

16.

Hahn A, Bode J, Kruwel T, Solecki G, Heiland S, Bendszus M . Glioblastoma multiforme restructures the topological connectivity of cerebrovascular networks. Sci Rep. 2019; 9(1):11757. PMC: 6692362. DOI: 10.1038/s41598-019-47567-w. View

17.

Sun F, Tang Z, Lui K, Ye S, Xue Q, Gao D . Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer. 1996; 66(2):239-43. DOI: 10.1002/(SICI)1097-0215(19960410)66:2<239::AID-IJC17>3.0.CO;2-7. View

18.

Fiebig T, Boll H, Figueiredo G, Kerl H, Nittka S, Groden C . Three-dimensional in vivo imaging of the murine liver: a micro-computed tomography-based anatomical study. PLoS One. 2012; 7(2):e31179. PMC: 3280110. DOI: 10.1371/journal.pone.0031179. View

19.

Jain R, Tomaso E, Duda D, Loeffler J, Sorensen A, Batchelor T . Angiogenesis in brain tumours. Nat Rev Neurosci. 2007; 8(8):610-22. DOI: 10.1038/nrn2175. View

20.

Moawad A, Szklaruk J, Lall C, Blair K, Kaseb A, Kamath A . Angiogenesis in Hepatocellular Carcinoma; Pathophysiology, Targeted Therapy, and Role of Imaging. J Hepatocell Carcinoma. 2020; 7:77-89. PMC: 7188073. DOI: 10.2147/JHC.S224471. View