Skip to main content
Top
Published in: Insights into Imaging 1/2023

Open Access 01-12-2023 | Magnetic Resonance Imaging | Original Article

Three-dimensional multifrequency magnetic resonance elastography improves preoperative assessment of proliferative hepatocellular carcinoma

Authors: Guixue Liu, Di Ma, Huafeng Wang, Jiahao Zhou, Zhehan Shen, Yuchen Yang, Yongjun Chen, Ingolf Sack, Jing Guo, Ruokun Li, Fuhua Yan

Published in: Insights into Imaging | Issue 1/2023

Login to get access

Abstract

Background

To investigate the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE).

Methods

This prospective study included 121 patients with 124 HCCs as training cohort, and validation cohort included 33 HCCs. They all underwent preoperative conventional magnetic resonance imaging (MRI) and tomoelastography based on 3D multifrequency MRE. Viscoelastic parameters of the tumor and liver were quantified as shear wave speed (c, m/s) and loss angle (φ, rad), representing stiffness and fluidity, respectively. Five MRI features were evaluated. Multivariate logistic regression analyses were used to determine predictors of proliferative HCC to construct corresponding nomograms.

Results

In training cohort, model 1 (Combining cirrhosis, hepatitis virus, rim APHE, peritumoral enhancement, and tumor margin) yielded an area under the curve (AUC), sensitivity, specificity, accuracy of 0.72, 58.73%,78.69%, 67.74%, respectively. When adding MRE properties (tumor c and tumor φ), established model 2, the AUC increased to 0.81 (95% CI 0.72–0.87), with sensitivity, specificity, accuracy of 71.43%, 81.97%, 75%, respectively. The C-index of nomogram of model 2 was 0.81, showing good performance for proliferative HCC. Therefore, integrating tumor c and tumor φ can significantly improve the performance of preoperative diagnosis of proliferative HCC (AUC increased from 0.72 to 0.81, p = 0.012). The same finding was observed in the validation cohort, with AUC increasing from 0.62 to 0.77 (p = 0.021).

Conclusions

Proliferative HCC exhibits low stiffness and high fluidity. Adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC.

Critical relevance statement

We investigated the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE), and find that adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC.

Graphical Abstract

Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Calderaro J, Ziol M, Paradis V, Zucman-Rossi J (2019) Molecular and histological correlations in liver cancer. J Hepatol 71(3):616–630PubMedCrossRef Calderaro J, Ziol M, Paradis V, Zucman-Rossi J (2019) Molecular and histological correlations in liver cancer. J Hepatol 71(3):616–630PubMedCrossRef
3.
go back to reference Nault JC, Martin Y, Caruso S et al (2020) Clinical impact of genomic diversity from early to advanced hepatocellular carcinoma. Hepatology 71(1):164–182PubMedCrossRef Nault JC, Martin Y, Caruso S et al (2020) Clinical impact of genomic diversity from early to advanced hepatocellular carcinoma. Hepatology 71(1):164–182PubMedCrossRef
4.
go back to reference Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM (2015) Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149(5):1226-1239 e1224PubMedCrossRef Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM (2015) Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149(5):1226-1239 e1224PubMedCrossRef
5.
go back to reference Calderaro J, Couchy G, Imbeaud S et al (2017) Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol 67(4):727–738PubMedCrossRef Calderaro J, Couchy G, Imbeaud S et al (2017) Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol 67(4):727–738PubMedCrossRef
6.
go back to reference Durnez A, Verslype C, Nevens F et al (2006) The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology 49(2):138–151PubMedCrossRef Durnez A, Verslype C, Nevens F et al (2006) The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology 49(2):138–151PubMedCrossRef
7.
go back to reference Chen J, Wu Z, Xia C et al (2020) Noninvasive prediction of HCC with progenitor phenotype based on gadoxetic acid-enhanced MRI. Eur Radiol 30(2):1232–1242PubMedCrossRef Chen J, Wu Z, Xia C et al (2020) Noninvasive prediction of HCC with progenitor phenotype based on gadoxetic acid-enhanced MRI. Eur Radiol 30(2):1232–1242PubMedCrossRef
8.
go back to reference Choi SY, Kim SH, Park CK et al (2018) Imaging features of gadoxetic acid-enhanced and diffusion-weighted MR imaging for identifying cytokeratin 19-positive hepatocellular carcinoma: a retrospective observational study. Radiology 286(3):897–908PubMedCrossRef Choi SY, Kim SH, Park CK et al (2018) Imaging features of gadoxetic acid-enhanced and diffusion-weighted MR imaging for identifying cytokeratin 19-positive hepatocellular carcinoma: a retrospective observational study. Radiology 286(3):897–908PubMedCrossRef
9.
go back to reference Hu XX, Wang WT, Yang L et al (2019) MR features based on LI-RADS identify cytokeratin 19 status of hepatocellular carcinomas. Eur J Radiol 113:7–14PubMedCrossRef Hu XX, Wang WT, Yang L et al (2019) MR features based on LI-RADS identify cytokeratin 19 status of hepatocellular carcinomas. Eur J Radiol 113:7–14PubMedCrossRef
10.
go back to reference Mulé S, Galletto Pregliasco A, Tenenhaus A et al (2020) Multiphase liver MRI for identifying the macrotrabecular-massive subtype of hepatocellular carcinoma. Radiology 295(3):562–571PubMedCrossRef Mulé S, Galletto Pregliasco A, Tenenhaus A et al (2020) Multiphase liver MRI for identifying the macrotrabecular-massive subtype of hepatocellular carcinoma. Radiology 295(3):562–571PubMedCrossRef
11.
go back to reference Kang HJ, Kim H, Lee DH et al (2021) Gadoxetate-enhanced MRI features of proliferative hepatocellular carcinoma are prognostic after surgery. Radiology 300(3):572–582PubMedCrossRef Kang HJ, Kim H, Lee DH et al (2021) Gadoxetate-enhanced MRI features of proliferative hepatocellular carcinoma are prognostic after surgery. Radiology 300(3):572–582PubMedCrossRef
12.
go back to reference Manduca A, Bayly PJ, Ehman RL et al (2021) MR elastography: principles, guidelines, and terminology. Magn Reson Med 85(5):2377–2390PubMedCrossRef Manduca A, Bayly PJ, Ehman RL et al (2021) MR elastography: principles, guidelines, and terminology. Magn Reson Med 85(5):2377–2390PubMedCrossRef
13.
go back to reference Pepin KM, McGee KP (2018) Quantifying tumor stiffness with magnetic resonance elastography: the role of mechanical properties for detection, characterization, and treatment stratification in oncology. Top Magn Reson Imaging 27(5):353–362PubMedCrossRef Pepin KM, McGee KP (2018) Quantifying tumor stiffness with magnetic resonance elastography: the role of mechanical properties for detection, characterization, and treatment stratification in oncology. Top Magn Reson Imaging 27(5):353–362PubMedCrossRef
14.
go back to reference Ingolf S (2022) Magnetic resonance elastography from fundamental soft-tissue mechanics to diagnostic imaging. Nat Rev Phys 5(1):25–42CrossRef Ingolf S (2022) Magnetic resonance elastography from fundamental soft-tissue mechanics to diagnostic imaging. Nat Rev Phys 5(1):25–42CrossRef
15.
go back to reference Reiter R, Tzschatzsch H, Schwahofer F et al (2020) Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis. Eur Radiol 30(3):1719–1729PubMedCrossRef Reiter R, Tzschatzsch H, Schwahofer F et al (2020) Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis. Eur Radiol 30(3):1719–1729PubMedCrossRef
16.
go back to reference Shahryari M, Tzschätzsch H, Guo J et al (2019) Tomoelastography distinguishes noninvasively between benign and malignant liver lesions. Can Res 79(22):5704–5710CrossRef Shahryari M, Tzschätzsch H, Guo J et al (2019) Tomoelastography distinguishes noninvasively between benign and malignant liver lesions. Can Res 79(22):5704–5710CrossRef
17.
go back to reference Gultekin E, Wetz C, Braun J et al (2021) Added value of tomoelastography for characterization of pancreatic neuroendocrine tumor aggressiveness based on stiffness. Cancers (Basel) 13(20):5185PubMedCrossRef Gultekin E, Wetz C, Braun J et al (2021) Added value of tomoelastography for characterization of pancreatic neuroendocrine tumor aggressiveness based on stiffness. Cancers (Basel) 13(20):5185PubMedCrossRef
18.
go back to reference Li M, Guo J, Hu P et al (2021) Tomoelastography based on multifrequency MR elastography for prostate cancer detection: comparison with multiparametric MRI. Radiology 299(2):362–370PubMedCrossRef Li M, Guo J, Hu P et al (2021) Tomoelastography based on multifrequency MR elastography for prostate cancer detection: comparison with multiparametric MRI. Radiology 299(2):362–370PubMedCrossRef
19.
go back to reference Hu X, Zhou J, Li Y et al (2022) Added value of viscoelasticity for MRI-based prediction of Ki-67 expression of Hepatocellular Carcinoma using a deep learning combined radiomics (DLCR) model. Cancers (Basel) 14(11):2575PubMedCrossRef Hu X, Zhou J, Li Y et al (2022) Added value of viscoelasticity for MRI-based prediction of Ki-67 expression of Hepatocellular Carcinoma using a deep learning combined radiomics (DLCR) model. Cancers (Basel) 14(11):2575PubMedCrossRef
20.
go back to reference Shahryari M, Meyer T, Warmuth C et al (2021) Reduction of breathing artifacts in multifrequency magnetic resonance elastography of the abdomen. Magn Reson Med 85(4):1962–1973PubMedCrossRef Shahryari M, Meyer T, Warmuth C et al (2021) Reduction of breathing artifacts in multifrequency magnetic resonance elastography of the abdomen. Magn Reson Med 85(4):1962–1973PubMedCrossRef
21.
go back to reference Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the study of liver diseases. Hepatology 68(2):723–750PubMedCrossRef Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the study of liver diseases. Hepatology 68(2):723–750PubMedCrossRef
22.
go back to reference Lee S, Kim SH, Lee JE, Sinn DH, Park CK (2017) Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol 67(3):526–534PubMedCrossRef Lee S, Kim SH, Lee JE, Sinn DH, Park CK (2017) Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol 67(3):526–534PubMedCrossRef
23.
go back to reference Wei Y, Huang Z, Tang H et al (2019) IVIM improves preoperative assessment of microvascular invasion in HCC. Eur Radiol 29(10):5403–5414PubMedCrossRef Wei Y, Huang Z, Tang H et al (2019) IVIM improves preoperative assessment of microvascular invasion in HCC. Eur Radiol 29(10):5403–5414PubMedCrossRef
24.
go back to reference Kim H, Jang M, Nyun PY (2020) Histopathological variants of hepatocellular carcinomas: an update according to the 5th edition of the WHO classification of digestive system tumors. J Liver Cancer 20(1):17–24CrossRef Kim H, Jang M, Nyun PY (2020) Histopathological variants of hepatocellular carcinomas: an update according to the 5th edition of the WHO classification of digestive system tumors. J Liver Cancer 20(1):17–24CrossRef
25.
go back to reference Wang W, Gu D, Wei J et al (2020) A radiomics-based biomarker for cytokeratin 19 status of hepatocellular carcinoma with gadoxetic acid-enhanced MRI. Eur Radiol 30(5):3004–3014PubMedCrossRef Wang W, Gu D, Wei J et al (2020) A radiomics-based biomarker for cytokeratin 19 status of hepatocellular carcinoma with gadoxetic acid-enhanced MRI. Eur Radiol 30(5):3004–3014PubMedCrossRef
26.
go back to reference Geng Z, Zhang Y, Wang S et al (2021) Radiomics analysis of susceptibility weighted imaging for hepatocellular carcinoma: exploring the correlation between histopathology and radiomics features. Magn Reson Med Sci 20(3):253–263PubMedCrossRef Geng Z, Zhang Y, Wang S et al (2021) Radiomics analysis of susceptibility weighted imaging for hepatocellular carcinoma: exploring the correlation between histopathology and radiomics features. Magn Reson Med Sci 20(3):253–263PubMedCrossRef
27.
28.
go back to reference Rebelo LM, de Sousa JS, Mendes Filho J, Radmacher M (2013) Comparison of the viscoelastic properties of cells from different kidney cancer phenotypes measured with atomic force microscopy. Nanotechnology 24(5):055102PubMedCrossRef Rebelo LM, de Sousa JS, Mendes Filho J, Radmacher M (2013) Comparison of the viscoelastic properties of cells from different kidney cancer phenotypes measured with atomic force microscopy. Nanotechnology 24(5):055102PubMedCrossRef
29.
go back to reference Chen YQ, Lan HY, Wu YC, Yang WH, Chiou A, Yang MH (2018) Epithelial-mesenchymal transition softens head and neck cancer cells to facilitate migration in 3D environments. J Cell Mol Med 22(8):3837–3846PubMedPubMedCentralCrossRef Chen YQ, Lan HY, Wu YC, Yang WH, Chiou A, Yang MH (2018) Epithelial-mesenchymal transition softens head and neck cancer cells to facilitate migration in 3D environments. J Cell Mol Med 22(8):3837–3846PubMedPubMedCentralCrossRef
30.
go back to reference Schrader J, Gordon-Walker TT, Aucott RL et al (2011) Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology 53(4):1192–1205PubMedCrossRef Schrader J, Gordon-Walker TT, Aucott RL et al (2011) Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology 53(4):1192–1205PubMedCrossRef
31.
go back to reference Mierke CT, Sauer F, Grosser S, Puder S, Fischer T, Käs JA (2018) The two faces of enhanced stroma: stroma acts as a tumor promoter and a steric obstacle. NMR Biomed 31(10):e3831PubMedCrossRef Mierke CT, Sauer F, Grosser S, Puder S, Fischer T, Käs JA (2018) The two faces of enhanced stroma: stroma acts as a tumor promoter and a steric obstacle. NMR Biomed 31(10):e3831PubMedCrossRef
32.
go back to reference Ray A, Provenzano PP (2021) Aligned forces: origins and mechanisms of cancer dissemination guided by extracellular matrix architecture. Curr Opin Cell Biol 72:63–71PubMedPubMedCentralCrossRef Ray A, Provenzano PP (2021) Aligned forces: origins and mechanisms of cancer dissemination guided by extracellular matrix architecture. Curr Opin Cell Biol 72:63–71PubMedPubMedCentralCrossRef
33.
34.
go back to reference Moeini A, Torrecilla S, Tovar V et al (2019) An immune gene expression signature associated with development of human hepatocellular carcinoma identifies mice that respond to chemopreventive agents. Gastroenterology 157(5):1383-1397 e1311PubMedCrossRef Moeini A, Torrecilla S, Tovar V et al (2019) An immune gene expression signature associated with development of human hepatocellular carcinoma identifies mice that respond to chemopreventive agents. Gastroenterology 157(5):1383-1397 e1311PubMedCrossRef
35.
go back to reference Rhee H, An C, Kim HY, Yoo JE, Park YN, Kim MJ (2019) Hepatocellular carcinoma with irregular rim-like arterial phase hyperenhancement: more aggressive pathologic features. Liver Cancer 8(1):24–40PubMedCrossRef Rhee H, An C, Kim HY, Yoo JE, Park YN, Kim MJ (2019) Hepatocellular carcinoma with irregular rim-like arterial phase hyperenhancement: more aggressive pathologic features. Liver Cancer 8(1):24–40PubMedCrossRef
36.
go back to reference Murakami K, Kasajima A, Kawagishi N, Ohuchi N, Sasano H (2015) Microvessel density in hepatocellular carcinoma: prognostic significance and review of the previous published work. Hepatol Res 45(12):1185–1194PubMedCrossRef Murakami K, Kasajima A, Kawagishi N, Ohuchi N, Sasano H (2015) Microvessel density in hepatocellular carcinoma: prognostic significance and review of the previous published work. Hepatol Res 45(12):1185–1194PubMedCrossRef
37.
go back to reference Banerjee S, Wang DS, Kim HJ et al (2015) A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatology 62(3):792–800PubMedCrossRef Banerjee S, Wang DS, Kim HJ et al (2015) A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatology 62(3):792–800PubMedCrossRef
38.
go back to reference An C, Kim DW, Park YN, Chung YE, Rhee H, Kim MJ (2015) Single hepatocellular carcinoma preoperative MR imaging to predict early recurrence after curative resection. Radiology 276(2):433–443PubMedCrossRef An C, Kim DW, Park YN, Chung YE, Rhee H, Kim MJ (2015) Single hepatocellular carcinoma preoperative MR imaging to predict early recurrence after curative resection. Radiology 276(2):433–443PubMedCrossRef
39.
go back to reference Rong D, Liu W, Kuang S et al (2021) Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. Eur Radiol 31(10):7584–7593PubMedCrossRef Rong D, Liu W, Kuang S et al (2021) Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. Eur Radiol 31(10):7584–7593PubMedCrossRef
40.
go back to reference Chou YC, Lao IH, Hsieh PL et al (2019) Gadoxetic acid-enhanced magnetic resonance imaging can predict the pathologic stage of solitary hepatocellular carcinoma. World J Gastroenterol 25(21):2636–2649PubMedPubMedCentralCrossRef Chou YC, Lao IH, Hsieh PL et al (2019) Gadoxetic acid-enhanced magnetic resonance imaging can predict the pathologic stage of solitary hepatocellular carcinoma. World J Gastroenterol 25(21):2636–2649PubMedPubMedCentralCrossRef
41.
go back to reference Wang WT, Yang L, Yang ZX et al (2018) Assessment of microvascular invasion of hepatocellular carcinoma with diffusion kurtosis imaging. Radiology 286(2):571–580PubMedCrossRef Wang WT, Yang L, Yang ZX et al (2018) Assessment of microvascular invasion of hepatocellular carcinoma with diffusion kurtosis imaging. Radiology 286(2):571–580PubMedCrossRef
42.
go back to reference Xu X, Zhang HL, Liu QP et al (2019) Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma. J Hepatol 70(6):1133–1144PubMedCrossRef Xu X, Zhang HL, Liu QP et al (2019) Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma. J Hepatol 70(6):1133–1144PubMedCrossRef
43.
go back to reference Renzulli M, Brocchi S, Cucchetti A et al (2016) Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology 279(2):432–442PubMedCrossRef Renzulli M, Brocchi S, Cucchetti A et al (2016) Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology 279(2):432–442PubMedCrossRef
Metadata
Title
Three-dimensional multifrequency magnetic resonance elastography improves preoperative assessment of proliferative hepatocellular carcinoma
Authors
Guixue Liu
Di Ma
Huafeng Wang
Jiahao Zhou
Zhehan Shen
Yuchen Yang
Yongjun Chen
Ingolf Sack
Jing Guo
Ruokun Li
Fuhua Yan
Publication date
01-12-2023
Publisher
Springer Vienna
Published in
Insights into Imaging / Issue 1/2023
Electronic ISSN: 1869-4101
DOI
https://doi.org/10.1186/s13244-023-01427-4

Other articles of this Issue 1/2023

Insights into Imaging 1/2023 Go to the issue