Abstract
Objectives
To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT).
Methods
Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated.
Results
In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group.
Conclusion
3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease.
Key Points
• 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients.
• The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.
Similar content being viewed by others
Abbreviations
- 2D:
-
Two-dimensional
- 3D:
-
Three-dimensional
- BA:
-
Biliary atresia
- CCD:
-
Charge-coupled device
- CK19:
-
Cytokeratin 19
- FBP:
-
Filtered back-projection algorithm
- HE:
-
Hematoxylin-eosin
- KP:
-
Kasai portoenterostomy
- LT:
-
Liver transplant
- PCCT:
-
X-ray phase-contrast computed tomography
- SMA:
-
Smooth muscle actin
- VOI:
-
Volumes of interest
References
Hartley JL, Davenport M, Kelly DA (2009) Biliary atresia. Lancet 374:1704–1713
Schuppan D, Afdhal NH (2008) Liver cirrhosis. Lancet 371:838–851
Sanyal AJ, Bosch J, Blei A, Arroyo V (2008) Portal hypertension and its complications. Gastroenterology 134:1715–1728
Aithal GP, Palaniyappan N, China L et al (2021) Guidelines on the management of ascites in cirrhosis. Gut 70:9–29
Bezerra JA, Wells RG, Mack CL et al (2018) Biliary atresia: clinical and research challenges for the twenty-first century. Hepatology 68:1163–1173
Caruso M, Cuocolo R, Di Dato F et al (2020) Ultrasound, shear-wave elastography, and magnetic resonance imaging in native liver survivor patients with biliary atresia after Kasai portoenterostomy: correlation with medical outcome after treatment. Acta Radiol 61:1300–1308
Asai A, Wu JF, Wang KS et al (2022) The outcome of patients with cystic biliary atresia with intact proximal hepatic ducts following hepatic-cyst-jejunostomy. J Pediatr Gastroenterol Nutr 75:131–137
Kato D, Uchida H, Amano H et al (2022) Laparoscopic revision of Kasai portoenterostomy after initial laparoscopic portoenterostomy in patients with biliary atresia: a limited but positive effect on native liver survival. Pediatr Surg Int 38:1821–1827
Okubo R, Nio M, Sasaki H, The Japanese Biliary Atresia Society (2021) Impacts of early Kasai portoenterostomy on short-term and long-term outcomes of biliary atresia. Hepatol Commun 5:234–243
Nio M, Wada M, Sasaki H, Kazama T, Tanaka H, Kudo H (2016) Technical standardization of Kasai portoenterostomy for biliary atresia. J Pediatr Surg 51:2105–2108
Yamamoto M, Ariizumi S (2018) Glissonean pedicle approach in liver surgery. Ann Gastroenterol Surg 2:124–128
Oetzmann von Sochaczewski C, Pintelon I, Brouns I et al (2019) Experimentally induced biliary atresia by means of rotavirus-infection is directly linked to severe damage of the microvasculature in the extrahepatic bile duct. Anat Rec 302:818–824
Obayashi J, Tanaka K, Ohyama K et al (2016) Relation between amount of bile ducts in portal canal and outcomes in biliary atresia. Pediatr Surg Int 32:833–838
Du J, Shi J, Liu J, Deng C, Shen J, Wang Q (2021) Hemodynamic analysis of hepatic arteries for the early evaluation of hepatic fibrosis in biliary atresia. Comput Methods Prog Biomed 211:106400
Wang Y, Xie X, Cao Q et al (2019) Quantitative contrast-enhanced ultrasound by Sonazoid in the early diagnosis of biliary atresia: an experimental study of rats with bile duct ligation. Ultrasound Med Biol 45:2767–2776
Masuya R, Muraji T, Ohtani H et al (2019) Morphometric demonstration of portal vein stenosis and hepatic arterial medial hypertrophy in patients with biliary atresia. Pediatr Surg Int 35:529–537
Yang J, Wei N, Su Y, Wei M, Yi B, Feng J (2020) A morphology-based analysis of biliary ductules after Kasai procedure and a review of the literature. J Surg Res 251:180–186
Noël PB, Herzen J, Fingerle AA et al (2013) Evaluation of the potential of phase-contrast computed tomography for improved visualization of cancerous human liver tissue. Z Med Phys 23:204–211
Kim YH, Kim M-J, Shin HJ et al (2018) MRI-based decision tree model for diagnosis of biliary atresia. Eur Radiol 28:3422–3431
Vallonthaiel AG, Baloda V, Singh L et al (2021) Histological analyses of trucut liver biopsies from patients with noncirrhotic portal fibrosis and extra-hepatic portal vein obstruction. Indian J Pathol Microbiol 64:S127–S135
Wilkins SW, Gureyev TE, Gao D, Pogany A, Stevenson AW (1996) Phase-contrast imaging using polychromatic hard X-rays. Nature 384:335–338
Jian J, Zhao X, Qin L et al (2019) Three-dimensional visualization of fibrous tissues in cirrhotic rats via X-ray phase-contrast computed tomography with iodine staining. J Synchrotron Radiat 26:1354–1360
Xin X, Xu H, Jian J et al (2022) A method of three-dimensional branching geometry to differentiate the intrahepatic vascular type in early-stage liver fibrosis using X-ray phase-contrast CT. Eur J Radiol 148:110178
Töpperwien M, van der Meer F, Stadelmann C, Salditt T (2020) Correlative x-ray phase-contrast tomography and histology of human brain tissue affected by Alzheimer’s disease. Neuroimage 210:116523
Jiang L, Li C, Li M et al (2021) Simultaneous 3D visualization of the microvascular and neural network in mouse spinal cord using synchrotron radiation micro-computed tomography. Neurosci Bull 37:1469–1480
Fingerle AA, Willner M, Herzen J et al (2014) Simulated cystic renal lesions: quantitative X-ray phase-contrast CT—an in vitro phantom study. Radiology 272:739–748
Auweter SD, Herzen J, Willner M et al (2014) X-ray phase-contrast imaging of the breast—advances towards clinical implementation. Br J Radiol 87:20130606
Sun M, Lv W, Zhao X et al (2020) Vascular branching geometry relating to portal hypertension: a study of liver microvasculature in cirrhotic rats by X-ray phase-contrast computed tomography. Quant Imaging Med Surg 10:116–127
Xuan R, Zhao X, Jian J et al (2019) Phase-contrast computed tomography: a correlation study between portal pressure and three dimensional microvasculature of ex vivo liver samples from carbon tetrachloride-induced liver fibrosis in rats. Microvasc Res 125:103884
Lv WJ, Zhao XY, Hu DD, Xin XH, Qin LL, Hu CH (2021) Insight into bile duct reaction to obstruction from a three-dimensional perspective using ex vivo phase-contrast CT. Radiology 299:597–610
Xie HL, Deng B, Du GH et al (2020) Methodology development and application of X-ray imaging beamline at SSRF. Nucl Sci Tech 31:102
Yamaguti DCC, da Silva Patrício FR (2011) Morphometrical and immunohistochemical study of intrahepatic bile ducts in biliary atresia. Eur J Gastroenterol Hepatol 23:759–765
Bessho K, Bezerra JA (2011) Biliary atresia: will blocking inflammation tame the disease? Annu Rev Med 62:171–185
Kim WS, Cheon J-E, Youn BJ et al (2007) Hepatic arterial diameter measured with US: adjunct for US diagnosis of biliary atresia. Radiology 245:549–555
Harumatsu T, Muraji T, Masuya R et al (2019) Microvascular proliferation of the portal vein branches in the liver of biliary atresia patients at Kasai operation is associated with a better long-term clinical outcome. Pediatr Surg Int 35:1437–1441
Yang L, Mizuochi T, Shivakumar P et al (2018) Regulation of epithelial injury and bile duct obstruction by NLRP3, IL-1R1 in experimental biliary atresia. J Hepatol 69:1136–1144
Ortiz-Perez A, Donnelly B, Temple H, Tiao G, Bansal R, Mohanty SK (2020) Innate immunity and pathogenesis of biliary atresia. Front Immunol 11:329
Clotman F (2004) Control of bile duct and hepatic artery development by liver-specific transcription factors. Bull Mem Acad R Med Belg 159:353–357
Fabris L, Cadamuro M, Fiorotto R et al (2006) Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases. Hepatology 43:1001–1012
Clotman F, Lannoy VJ, Reber M et al (2002) The onecut transcription factor HNF6 is required for normal development of the biliary tract. Development 129:1819–1828
Patel KR, Harpavat S, Khan Z et al (2020) Biliary atresia patients with successful Kasai portoenterostomy can present with features of obliterative portal venopathy. J Pediatr Gastroenterol Nutr 71:91–98
Acknowledgements
Thanks to the BL13HB Beamline and all the staff at Shanghai Synchrotron Radiation Facility.
Funding
This work was supported by the National Natural Science Foundation of China under Grant Nos. 82071922, 82102037, 82001813, and 81671683; and Tianjin Municipal Education Commission under Grant No. 2020KJ208.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Guarantor
The scientific guarantor of this publication is Chun-Hong Hu.
Conflict of interest
The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
Statistics and biometry
No complex statistical methods were necessary for this paper.
Informed consent
Written informed consent was waived by the Institutional Review Board.
Ethical approval
Institutional Review Board approval was obtained.
Methodology
• retrospective
• cross-sectional study
• performed at one institution
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
ESM 1
(DOCX 863 kb)
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Qi, BN., Lv, WJ., Jian, JB. et al. Insight into microvascular adaptive alterations in the Glisson system of biliary atresia after Kasai portoenterostomy using X-ray phase-contrast CT. Eur Radiol 33, 4082–4093 (2023). https://doi.org/10.1007/s00330-022-09364-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00330-022-09364-4