Skip to main content
Top
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Preoperative diagnosis and prediction of hepatocellular carcinoma: Radiomics analysis based on multi-modal ultrasound images

Authors: Zhao Yao, Yi Dong, Guoqing Wu, Qi Zhang, Daohui Yang, Jin-Hua Yu, Wen-Ping Wang

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

This study aims to establish a radiomics analysis system for the diagnosis and clinical behaviour prediction of hepatocellular carcinoma (HCC) based on multi-parametric ultrasound imaging.

Methods

A total of 177 patients with focal liver lesions (FLLs) were included in the study. Every patient underwent multi-modal ultrasound examination, including B-mode ultrasound (BMUS), shear wave elastography (SWE), and shear wave viscosity (SWV) imaging. The radiomics analysis system was built on sparse representation theory (SRT) and support vector machine (SVM) for asymmetric data. Through the sparse regulation from the SRT, the proposed radiomics system can effectively avoid over-fitting issues that occur in regular radiomics analysis. The purpose of the proposed system includes differential diagnosis between benign and malignant FLLs, pathologic diagnosis of HCC, and clinical prognostic prediction. Three biomarkers, including programmed cell death protein 1 (PD-1), antigen Ki-67 (Ki-67) and microvascular invasion (MVI), were included and analysed. We calculated the accuracy (ACC), sensitivity (SENS), specificity (SPEC) and area under the receiver operating characteristic curve (AUC) to evaluate the performance of the radiomics models.

Results

A total of 2560 features were extracted from the multi-modal ultrasound images for each patient. Five radiomics models were built, and leave-one-out cross-validation (LOOCV) was used to evaluate the models. In LOOCV, the AUC was 0.94 for benign and malignant classification (95% confidence interval [CI]: 0.88 to 0.98), 0.97 for malignant subtyping (95% CI: 0.93 to 0.99), 0.97 for PD-1 prediction (95% CI: 0.89 to 0.98), 0.94 for Ki-67 prediction (95% CI: 0.87 to 0.97), and 0.98 for MVI prediction (95% CI: 0.93 to 0.99). The performance of each model improved when the viscosity modality was included.

Conclusions

Radiomics analysis based on multi-modal ultrasound images could aid in comprehensive liver tumor evaluations, including diagnosis, differential diagnosis, and clinical prognosis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–14.CrossRef Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–14.CrossRef
2.
go back to reference Samir AE, Dhyani M, Vij A, Bhan AK, Halpern EF, Mendez-Navarro J, Corey KE, Chung RT. Shear-wave Elastography for the estimation of liver fibrosis in chronic liver disease: determining accuracy and ideal site for measurement. Radiology. 2015;274(3):888–96.CrossRef Samir AE, Dhyani M, Vij A, Bhan AK, Halpern EF, Mendez-Navarro J, Corey KE, Chung RT. Shear-wave Elastography for the estimation of liver fibrosis in chronic liver disease: determining accuracy and ideal site for measurement. Radiology. 2015;274(3):888–96.CrossRef
3.
go back to reference Conti CB, Cavalcoli F, Fraquelli M, Conte D, Massironi S. Ultrasound elastographic techniques in focal liver lesions. World J Gastroenterol. 2016;22(9):2647–56.CrossRef Conti CB, Cavalcoli F, Fraquelli M, Conte D, Massironi S. Ultrasound elastographic techniques in focal liver lesions. World J Gastroenterol. 2016;22(9):2647–56.CrossRef
4.
go back to reference Xie LT, Yan CH, Zhao QY, He MN, Jiang TA. Quantitative and noninvasive assessment of chronic liver diseases using two-dimensional shear wave elastography. World J Gastroenterol. 2018;24(9):957–70.CrossRef Xie LT, Yan CH, Zhao QY, He MN, Jiang TA. Quantitative and noninvasive assessment of chronic liver diseases using two-dimensional shear wave elastography. World J Gastroenterol. 2018;24(9):957–70.CrossRef
5.
go back to reference Gillies RJ, Kinahan PE, Hricak H. Radiomics: images are more than pictures, They Are Data. Radiology. 2016;278(2):563–77.CrossRef Gillies RJ, Kinahan PE, Hricak H. Radiomics: images are more than pictures, They Are Data. Radiology. 2016;278(2):563–77.CrossRef
6.
go back to reference Acharya UR, Hagiwara Y, Sudarshan VK, Chan WY, Ng KH. Towards precision medicine: from quantitative imaging to radiomics. J Zhejiang Univ Sci B. 2018;19(1):6–24.CrossRef Acharya UR, Hagiwara Y, Sudarshan VK, Chan WY, Ng KH. Towards precision medicine: from quantitative imaging to radiomics. J Zhejiang Univ Sci B. 2018;19(1):6–24.CrossRef
7.
go back to reference Virmani J, Kumar V, Kalra N, Khandelwal N. SVM-based characterization of liver ultrasound images using wavelet packet texture descriptors. J Digit Imaging. 2013;26(3):530–43.CrossRef Virmani J, Kumar V, Kalra N, Khandelwal N. SVM-based characterization of liver ultrasound images using wavelet packet texture descriptors. J Digit Imaging. 2013;26(3):530–43.CrossRef
8.
go back to reference Owjimehr M, Danyali H, Helfroush MS. An improved method for liver diseases detection by ultrasound image analysis. J Med Signals Sens. 2015;5(1):21–9.PubMedPubMedCentral Owjimehr M, Danyali H, Helfroush MS. An improved method for liver diseases detection by ultrasound image analysis. J Med Signals Sens. 2015;5(1):21–9.PubMedPubMedCentral
9.
go back to reference Kalyan K, Jakhia B, Lele RD, Joshi M, Chowdhary A. Artificial neural network application in the diagnosis of disease conditions with liver ultrasound images. Adv Bioinforma. 2014;2014:708279.CrossRef Kalyan K, Jakhia B, Lele RD, Joshi M, Chowdhary A. Artificial neural network application in the diagnosis of disease conditions with liver ultrasound images. Adv Bioinforma. 2014;2014:708279.CrossRef
10.
go back to reference Bharti P, Mittal D, Ananthasivan R. Preliminary study of chronic liver classification on ultrasound images using an ensemble model. Ultrason Imaging. 2018:161734618787447. Bharti P, Mittal D, Ananthasivan R. Preliminary study of chronic liver classification on ultrasound images using an ensemble model. Ultrason Imaging. 2018:161734618787447.
11.
go back to reference Sugimoto K, Shiraishi J, Tanaka H, Tsuchiya K, Aso K, Kobayashi Y, Iijima H, Moriyasu F. Computer-aided diagnosis for estimating the malignancy grade of hepatocellular carcinoma using contrast-enhanced ultrasound: an ROC observer study. Liver Int. 2016;36(7):1026–32.CrossRef Sugimoto K, Shiraishi J, Tanaka H, Tsuchiya K, Aso K, Kobayashi Y, Iijima H, Moriyasu F. Computer-aided diagnosis for estimating the malignancy grade of hepatocellular carcinoma using contrast-enhanced ultrasound: an ROC observer study. Liver Int. 2016;36(7):1026–32.CrossRef
12.
go back to reference Lin DD, Cao HB, Calhoun VD, Wang YP. Sparse models for correlative and integrative analysis of imaging and genetic data. J Neurosci Methods. 2014;237:69–78.CrossRef Lin DD, Cao HB, Calhoun VD, Wang YP. Sparse models for correlative and integrative analysis of imaging and genetic data. J Neurosci Methods. 2014;237:69–78.CrossRef
13.
go back to reference Cao HB, Duan JB, Lin DD, Shugart YY, Calhoun V, Wang YP. Sparse representation based biomarker selection for schizophrenia with integrated analysis of fMRI and SNPs. Neuroimage. 2014;102:220–8.CrossRef Cao HB, Duan JB, Lin DD, Shugart YY, Calhoun V, Wang YP. Sparse representation based biomarker selection for schizophrenia with integrated analysis of fMRI and SNPs. Neuroimage. 2014;102:220–8.CrossRef
14.
go back to reference Yuan XT, Liu XB, Yan SC. Visual classification with multitask joint sparse representation. IEEE Trans Image Process. 2012;21(10):4349–60.CrossRef Yuan XT, Liu XB, Yan SC. Visual classification with multitask joint sparse representation. IEEE Trans Image Process. 2012;21(10):4349–60.CrossRef
15.
go back to reference Zhang HC, Nasrabadi NM, Zhang YN, Huang TS. Multi-observation visual recognition via joint dynamic sparse representation. 2011 IEEE Int Conf Comput Vision (Iccv) 2011:595–602. Zhang HC, Nasrabadi NM, Zhang YN, Huang TS. Multi-observation visual recognition via joint dynamic sparse representation. 2011 IEEE Int Conf Comput Vision (Iccv) 2011:595–602.
16.
go back to reference Wu GQ, Chen YS, Wang YY, Yu JH, Lv XF, Ju X, Shi ZF, Chen L, Chen ZP. Sparse representation-based Radiomics for the diagnosis of brain tumors. IEEE Trans Med Imaging. 2018;37(4):893–905.CrossRef Wu GQ, Chen YS, Wang YY, Yu JH, Lv XF, Ju X, Shi ZF, Chen L, Chen ZP. Sparse representation-based Radiomics for the diagnosis of brain tumors. IEEE Trans Med Imaging. 2018;37(4):893–905.CrossRef
17.
go back to reference Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, Cosgrove D, Ferraioli G, Friedrich-Rust M, Gilja OH, et al. EFSUMB guidelines and recommendations on the clinical use of liver ultrasound Elastography, update 2017 (long version). Ultraschall Med. 2017;38(4):e16–47.CrossRef Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, Cosgrove D, Ferraioli G, Friedrich-Rust M, Gilja OH, et al. EFSUMB guidelines and recommendations on the clinical use of liver ultrasound Elastography, update 2017 (long version). Ultraschall Med. 2017;38(4):e16–47.CrossRef
18.
go back to reference Aharon M, Elad M, Bruckstein A. K-SVD: an algorithm for designing overcomplete dictionaries for sparse representation. IEEE Trans Signal Process. 2006;54(11):4311–22.CrossRef Aharon M, Elad M, Bruckstein A. K-SVD: an algorithm for designing overcomplete dictionaries for sparse representation. IEEE Trans Signal Process. 2006;54(11):4311–22.CrossRef
19.
go back to reference Chang CC, Lin CJ. LIBSVM: a library for support vector machines. ACM Trans Intell Syst Technol. 2011;2(3):13–5.CrossRef Chang CC, Lin CJ. LIBSVM: a library for support vector machines. ACM Trans Intell Syst Technol. 2011;2(3):13–5.CrossRef
20.
go back to reference Dong Y, Wang WP, Xu Y, Cao J, Mao F, Dietrich CF. Point shear wave speed measurement in differentiating benign and malignant focal liver lesions. Med Ultrason. 2017;19(3):259–64.CrossRef Dong Y, Wang WP, Xu Y, Cao J, Mao F, Dietrich CF. Point shear wave speed measurement in differentiating benign and malignant focal liver lesions. Med Ultrason. 2017;19(3):259–64.CrossRef
21.
go back to reference Ozmen E, Adaletli I, Kayadibi Y, Emre S, Kilic F, Dervisoglu S, Kurugoglu S, Senyuz OF. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population. Eur J Radiol. 2014;83(9):1691–7.CrossRef Ozmen E, Adaletli I, Kayadibi Y, Emre S, Kilic F, Dervisoglu S, Kurugoglu S, Senyuz OF. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population. Eur J Radiol. 2014;83(9):1691–7.CrossRef
22.
go back to reference Lewis RB, Lattin GE Jr, Makhlouf HR, Levy AD. Tumors of the liver and intrahepatic bile ducts: radiologic-pathologic correlation. Magn Reson Imaging Clin N Am. 2010;18(3):587–609 xii.CrossRef Lewis RB, Lattin GE Jr, Makhlouf HR, Levy AD. Tumors of the liver and intrahepatic bile ducts: radiologic-pathologic correlation. Magn Reson Imaging Clin N Am. 2010;18(3):587–609 xii.CrossRef
23.
go back to reference Ippolito D, Inchingolo R, Grazioli L, Drago SG, Nardella M, Gatti M, Faletti R. Recent advances in non-invasive magnetic resonance imaging assessment of hepatocellular carcinoma. World J Gastroenterol. 2018;24(23):2413–26.CrossRef Ippolito D, Inchingolo R, Grazioli L, Drago SG, Nardella M, Gatti M, Faletti R. Recent advances in non-invasive magnetic resonance imaging assessment of hepatocellular carcinoma. World J Gastroenterol. 2018;24(23):2413–26.CrossRef
24.
go back to reference Bird TG, Dimitropoulou P, Turner RM, Jenks SJ, Cusack P, Hey S, Blunsum A, Kelly S, Sturgeon C, Hayes PC, et al. Alpha-fetoprotein detection of hepatocellular carcinoma leads to a standardized analysis of dynamic AFP to improve screening based detection. PLoS One. 2016;11(6):e0156801.CrossRef Bird TG, Dimitropoulou P, Turner RM, Jenks SJ, Cusack P, Hey S, Blunsum A, Kelly S, Sturgeon C, Hayes PC, et al. Alpha-fetoprotein detection of hepatocellular carcinoma leads to a standardized analysis of dynamic AFP to improve screening based detection. PLoS One. 2016;11(6):e0156801.CrossRef
25.
go back to reference Janevska D, Chaloska-Ivanova V, Janevski V. Hepatocellular carcinoma: risk factors, diagnosis and treatment. Open Access Maced J Med Sci. 2015;3(4):732–6.CrossRef Janevska D, Chaloska-Ivanova V, Janevski V. Hepatocellular carcinoma: risk factors, diagnosis and treatment. Open Access Maced J Med Sci. 2015;3(4):732–6.CrossRef
26.
go back to reference Unal E, Idilman IS, Akata D, Ozmen MN, Karcaaltincaba M. Microvascular invasion in hepatocellular carcinoma. Diagn Interv Radiol. 2016;22(2):125–32.CrossRef Unal E, Idilman IS, Akata D, Ozmen MN, Karcaaltincaba M. Microvascular invasion in hepatocellular carcinoma. Diagn Interv Radiol. 2016;22(2):125–32.CrossRef
27.
go back to reference Renzulli M, Buonfiglioli F, Conti F, Brocchi S, Serio I, Foschi FG, Caraceni P, Mazzella G, Verucchi G, Golfieri R, et al. Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis. Eur Radiol. 2018;28(2):506–13.CrossRef Renzulli M, Buonfiglioli F, Conti F, Brocchi S, Serio I, Foschi FG, Caraceni P, Mazzella G, Verucchi G, Golfieri R, et al. Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis. Eur Radiol. 2018;28(2):506–13.CrossRef
28.
go back to reference Lee S, Kim SH, Lee JE, Sinn DH, Park CK. Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol. 2017;67(3):526–34.CrossRef Lee S, Kim SH, Lee JE, Sinn DH, Park CK. Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol. 2017;67(3):526–34.CrossRef
29.
go back to reference Banerjee S, Wang DS, Kim HJ, Sirlin CB, Chan MG, Korn RL, Rutman AM, Siripongsakun S, Lu D, Imanbayev G, et al. A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatology. 2015;62(3):792–800.CrossRef Banerjee S, Wang DS, Kim HJ, Sirlin CB, Chan MG, Korn RL, Rutman AM, Siripongsakun S, Lu D, Imanbayev G, et al. A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatology. 2015;62(3):792–800.CrossRef
30.
go back to reference Renzulli M, Brocchi S, Cucchetti A, Mazzotti F, Mosconi C, Sportoletti C, Brandi G, Pinna AD, Golfieri R. Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology. 2016;279(2):432–42.CrossRef Renzulli M, Brocchi S, Cucchetti A, Mazzotti F, Mosconi C, Sportoletti C, Brandi G, Pinna AD, Golfieri R. Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology. 2016;279(2):432–42.CrossRef
31.
go back to reference Peng J, Zhang J, Zhang Q, Xu Y, Zhou J, Liu L. A radiomics nomogram for preoperative prediction of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma. Diagn Interv Radiol. 2018;24(3):121–7.CrossRef Peng J, Zhang J, Zhang Q, Xu Y, Zhou J, Liu L. A radiomics nomogram for preoperative prediction of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma. Diagn Interv Radiol. 2018;24(3):121–7.CrossRef
32.
go back to reference Luo Y, Ren F, Liu Y, Shi Z, Tan Z, Xiong H, Dang Y, Chen G. Clinicopathological and prognostic significance of high Ki-67 labeling index in hepatocellular carcinoma patients: a meta-analysis. Int J Clin Exp Med. 2015;8(7):10235–47.PubMedPubMedCentral Luo Y, Ren F, Liu Y, Shi Z, Tan Z, Xiong H, Dang Y, Chen G. Clinicopathological and prognostic significance of high Ki-67 labeling index in hepatocellular carcinoma patients: a meta-analysis. Int J Clin Exp Med. 2015;8(7):10235–47.PubMedPubMedCentral
33.
go back to reference Stroescu C, Dragnea A, Ivanov B, Pechianu C, Herlea V, Sgarbura O, Popescu A, Popescu I. Expression of p53, Bcl-2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma. J Gastrointestin Liver Dis. 2008;17(4):411–7.PubMed Stroescu C, Dragnea A, Ivanov B, Pechianu C, Herlea V, Sgarbura O, Popescu A, Popescu I. Expression of p53, Bcl-2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma. J Gastrointestin Liver Dis. 2008;17(4):411–7.PubMed
34.
go back to reference Shi W, Hu JF, Zhu SZ, Shen XY, Zhang XY, Yang CQ, Gao HJ, Zhang H. Expression of MTA2 and Ki-67 in hepatocellular carcinoma and their correlation with prognosis. Int J Clin Exp Pathol. 2015;8(10):13083–9.PubMedPubMedCentral Shi W, Hu JF, Zhu SZ, Shen XY, Zhang XY, Yang CQ, Gao HJ, Zhang H. Expression of MTA2 and Ki-67 in hepatocellular carcinoma and their correlation with prognosis. Int J Clin Exp Pathol. 2015;8(10):13083–9.PubMedPubMedCentral
35.
go back to reference Takata H, Kudo M, Yamamoto T, Ueda J, Ishino K, Peng WX, Wada R, Taniai N, Yoshida H, Uchida E, et al. Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma. Oncol Lett. 2016;12(6):4896–904.CrossRef Takata H, Kudo M, Yamamoto T, Ueda J, Ishino K, Peng WX, Wada R, Taniai N, Yoshida H, Uchida E, et al. Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma. Oncol Lett. 2016;12(6):4896–904.CrossRef
36.
go back to reference Xu F, Jin T, Zhu Y, Dai C. Immune checkpoint therapy in liver cancer. J Exp Clin Cancer Res. 2018;37(1):110.CrossRef Xu F, Jin T, Zhu Y, Dai C. Immune checkpoint therapy in liver cancer. J Exp Clin Cancer Res. 2018;37(1):110.CrossRef
37.
go back to reference Shi F, Shi M, Zeng Z, Qi RZ, Liu ZW, Zhang JY, Yang YP, Tien P, Wang FS. PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer. 2011;128(4):887–96.CrossRef Shi F, Shi M, Zeng Z, Qi RZ, Liu ZW, Zhang JY, Yang YP, Tien P, Wang FS. PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer. 2011;128(4):887–96.CrossRef
Metadata
Title
Preoperative diagnosis and prediction of hepatocellular carcinoma: Radiomics analysis based on multi-modal ultrasound images
Authors
Zhao Yao
Yi Dong
Guoqing Wu
Qi Zhang
Daohui Yang
Jin-Hua Yu
Wen-Ping Wang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5003-4

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine