Abdominal Radiology

, Volume 44, Issue 3, pp 912–922 | Cite as

Volumetric quantitative histogram analysis using diffusion-weighted magnetic resonance imaging to differentiate HCC from other primary liver cancers

  • Sara LewisEmail author
  • Steven Peti
  • Stefanie J. Hectors
  • Michael King
  • Ally Rosen
  • Amita Kamath
  • Juan Putra
  • Swan Thung
  • Bachir Taouli



To evaluate the ability of volumetric quantitative apparent diffusion coefficient (ADC) histogram parameters and LI-RADS categorization to distinguish hepatocellular carcinoma (HCC) from other primary liver cancers [intrahepatic cholangiocarcinoma (ICC) and combined HCC-ICC].


Sixty-three consecutive patients (44 M/19F; mean age 62 years) with primary liver cancers and pre-treatment MRI including diffusion-weighted imaging (DWI) were included in this IRB-approved single-center retrospective study. Tumor type was categorized pathologically. Qualitative tumor features and LI-RADS categorization were assessed by 2 independent observers. Lesion volume of interest measurements (VOIs) were placed on ADC maps to extract first-order radiomics (histogram) features. ADC histogram metrics and qualitative findings were compared. Binary logistic regression and AUROC were used to assess performance for distinction of HCC from ICC and combined tumors.


Sixty-five lesions (HCC, n = 36; ICC, n = 17; and combined tumor, n = 12) were assessed. Only enhancement pattern (p < 0.015) and capsule were useful for tumor diagnosis (p < 0.014). ADC 5th/10th/95th percentiles were significant for discrimination between each tumor types (all p values < 0.05). Accuracy of LI-RADS for HCC diagnosis was 76.9% (p < 0.0001) and 69.2% (p = 0.001) for both observers. The combination of male gender, LI-RADS, and ADC 5th percentile yielded an AUROC/sensitivity/specificity/accuracy of 0.90/79.3%/88.9%/81.5% and 0.89/86.2%/77.8%/80.0% (all p values < 0.027) for the diagnosis of HCC compared to ICC and combined tumors for both observers, respectively.


The combination of quantitative ADC histogram parameters and LI-RADS categorization yielded the best prediction accuracy for distinction of HCC compared to ICC and combined HCC-ICC.


Diffusion-weighted imaging (DWI) Apparent diffusion coefficient (ADC) Hepatocellular carcinoma (HCC) Intrahepatic cholangiocarcinoma (ICC) Combined HCC-ICC Histogram Tumor grade 



No funding was provided for this study.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Supplementary material

261_2019_1906_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 19 kb)


  1. 1.
    Tomimatsu M, Ishiguro N, Taniai M, et al. (1993) Hepatitis C virus antibody in patients with primary liver cancer (hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma) in Japan. Cancer 72:683–688CrossRefGoogle Scholar
  2. 2.
    Nakanuma Y, Xu J, Harada K, et al. (2011) Pathological spectrum of intrahepatic cholangiocarcinoma arising in non-biliary chronic advanced liver diseases. Pathol Int 61:298–305CrossRefGoogle Scholar
  3. 3.
    Portolani N, Baiocchi GL, Coniglio A, et al. (2008) Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience. Ann Surg Oncol 15:1880–1890CrossRefGoogle Scholar
  4. 4.
    Weber SM, Ribero D, O’Reilly EM, et al. (2015) Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford) 17:669–680Google Scholar
  5. 5.
    Fowler KJ, Sheybani A, Parker RA 3rd, et al. (2013) Combined hepatocellular and cholangiocarcinoma (biphenotypic) tumors: imaging features and diagnostic accuracy of contrast-enhanced CT and MRI. AJR Am J Roentgenol 201:332–339CrossRefGoogle Scholar
  6. 6.
    Jarnagin WR, Weber S, Tickoo SK, et al. (2002) Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer 94:2040–2046CrossRefGoogle Scholar
  7. 7.
    Lee JH, Chung GE, Yu SJ, et al. (2011) Long-term prognosis of combined hepatocellular and cholangiocarcinoma after curative resection comparison with hepatocellular carcinoma and cholangiocarcinoma. J Clin Gastroenterol 45:69–75Google Scholar
  8. 8.
    Dodson RM, Weiss MJ, Cosgrove D, et al. (2013) Intrahepatic cholangiocarcinoma: management options and emerging therapies. J Am Coll Surg 217(736–750):e734Google Scholar
  9. 9.
    Bruix J, Reig M, Sherman M (2016) Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology 150:835–853CrossRefGoogle Scholar
  10. 10.
    Kis B, El-Haddad G, Sheth RA, et al. (2017) Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 24:1073274817729244CrossRefGoogle Scholar
  11. 11.
    Bruix J, Sherman M, American Association for the Study of Liver D (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022CrossRefGoogle Scholar
  12. 12.
    Xu J, Igarashi S, Sasaki M, et al. (2012) Intrahepatic cholangiocarcinomas in cirrhosis are hypervascular in comparison with those in normal livers. Liver Int 32:1156–1164CrossRefGoogle Scholar
  13. 13.
    Potretzke TA, Tan BR, Doyle MB, et al. (2016) Imaging Features of Biphenotypic Primary Liver Carcinoma (Hepatocholangiocarcinoma) and the Potential to Mimic Hepatocellular Carcinoma: LI-RADS Analysis of CT and MRI Features in 61 Cases. AJR Am J Roentgenol 207:25–31CrossRefGoogle Scholar
  14. 14.
    Huang B, Wu L, Lu XY, et al. (2016) Small Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma in Cirrhotic Livers May Share Similar Enhancement Patterns at Multiphase Dynamic MR Imaging. Radiology 281:150–157CrossRefGoogle Scholar
  15. 15.
    Sheng RF, Xie YH, Ji Y, et al. (2016) MR comparative study of combined hepatocellular-cholangiocarcinoma in normal, fibrotic, and cirrhotic livers. Abdom Radiol (NY) 41:2102–2114CrossRefGoogle Scholar
  16. 16.
    Sheng RF, Zeng MS, Rao SX, Ji Y, Chen LL (2014) MRI of small intrahepatic mass-forming cholangiocarcinoma and atypical small hepatocellular carcinoma (</=3 cm) with cirrhosis and chronic viral hepatitis: a comparative study. Clin Imaging 38:265–272CrossRefGoogle Scholar
  17. 17.
    Piccinino F, Sagnelli E, Pasquale G, Giusti G (1986) Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol 2:165–173CrossRefGoogle Scholar
  18. 18.
    Chernyak V, Santillan CS, Papadatos D, Sirlin CB (2018) LI-RADS((R)) algorithm: CT and MRI. Abdom Radiol (NY) 43:111–126CrossRefGoogle Scholar
  19. 19.
    Galea N, Cantisani V, Taouli B (2013) Liver lesion detection and characterization: role of diffusion-weighted imaging. J Magn Reson Imaging 37:1260–1276CrossRefGoogle Scholar
  20. 20.
    Lewis S, Dyvorne H, Cui Y, Taouli B (2014) Diffusion-weighted imaging of the liver: techniques and applications. Magn Reson Imaging Clin N Am 22:373–395CrossRefGoogle Scholar
  21. 21.
    Bruegel M, Holzapfel K, Gaa J, et al. (2008) Characterization of focal liver lesions by ADC measurements using a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging technique. Eur Radiol 18:477–485CrossRefGoogle Scholar
  22. 22.
    Parikh T, Drew SJ, Lee VS, et al. (2008) Focal liver lesion detection and characterization with diffusion-weighted MR imaging: comparison with standard breath-hold T2-weighted imaging. Radiology 246:812–822CrossRefGoogle Scholar
  23. 23.
    Lewis S, Besa C, Wagner M et al (2017) Prediction of the histopathologic findings of intrahepatic cholangiocarcinoma: qualitative and quantitative assessment of diffusion-weighted imaging. Eur Radiol. 10.1007/s00330-017-5156-6Google Scholar
  24. 24.
    Testa ML, Chojniak R, Sene LS, et al. (2014) Is DWI/ADC a useful tool in the characterization of focal hepatic lesions suspected of malignancy? PLoS One 9:e101944CrossRefGoogle Scholar
  25. 25.
    Nakanishi M, Chuma M, Hige S, et al. (2012) Relationship between diffusion-weighted magnetic resonance imaging and histological tumor grading of hepatocellular carcinoma. Ann Surg Oncol 19:1302–1309CrossRefGoogle Scholar
  26. 26.
    Gillies RJ, Kinahan PE, Hricak H (2016) Radiomics: Images Are More than Pictures, They Are Data. Radiology 278:563–577CrossRefGoogle Scholar
  27. 27.
    Drevelegas K, Nikiforaki K, Constantinides M, et al. (2016) Apparent Diffusion Coefficient Quantification in Determining the Histological Diagnosis of Malignant Liver Lesions. J Cancer 7:730–735CrossRefGoogle Scholar
  28. 28.
    Moriya T, Saito K, Tajima Y, et al. (2017) 3D analysis of apparent diffusion coefficient histograms in hepatocellular carcinoma: correlation with histological grade. Cancer Imaging 17:1CrossRefGoogle Scholar
  29. 29.
    Khatri G, Merrick L, Miller FH (2010) MR imaging of hepatocellular carcinoma. Magn Reson Imaging Clin N Am 18(421–450):xGoogle Scholar
  30. 30.
    Just N (2014) Improving tumour heterogeneity MRI assessment with histograms. Br J Cancer 111:2205–2213CrossRefGoogle Scholar
  31. 31.
    Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503CrossRefGoogle Scholar
  32. 32.
    Washington MK, Berlin J, Branton PA, et al. (2010) Protocol for the examination of specimens from patients with carcinoma of the intrahepatic bile ducts. Arch Pathol Lab Med 134:e14–18Google Scholar
  33. 33.
    Doshi AM, Ream JM, Kierans AS, et al. (2016) Use of MRI in Differentiation of Papillary Renal Cell Carcinoma Subtypes: Qualitative and Quantitative Analysis. AJR Am J Roentgenol 206:566–572CrossRefGoogle Scholar
  34. 34.
    Chung YE, Kim MJ, Park YN, et al. (2009) Varying appearances of cholangiocarcinoma: radiologic-pathologic correlation. Radiographics 29:683–700CrossRefGoogle Scholar
  35. 35.
    Wald C, Russo MW, Heimbach JK, et al. (2013) New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma. Radiology 266:376–382CrossRefGoogle Scholar
  36. 36.
    Horvat N, Nikolovski I, Long N, et al. (2018) Imaging features of hepatocellular carcinoma compared to intrahepatic cholangiocarcinoma and combined tumor on MRI using liver imaging and data system (LI-RADS) version 2014. Abdom Radiol (NY) 43:169–178CrossRefGoogle Scholar
  37. 37.
    Davenport MS, Khalatbari S, Liu PS, et al. (2014) Repeatability of diagnostic features and scoring systems for hepatocellular carcinoma by using MR imaging. Radiology 272:132–142CrossRefGoogle Scholar
  38. 38.
    Bashir MR, Huang R, Mayes N, et al. (2015) Concordance of hypervascular liver nodule characterization between the organ procurement and transplant network and liver imaging reporting and data system classifications. J Magn Reson Imaging 42:305–314CrossRefGoogle Scholar
  39. 39.
    Kim T, Murakami T, Takahashi S, et al. (1999) Diffusion-weighted single-shot echoplanar MR imaging for liver disease. AJR Am J Roentgenol 173:393–398CrossRefGoogle Scholar
  40. 40.
    Taouli B, Vilgrain V, Dumont E, et al. (2003) Evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo-planar MR imaging sequences: prospective study in 66 patients. Radiology 226:71–78CrossRefGoogle Scholar
  41. 41.
    Gourtsoyianni S, Papanikolaou N, Yarmenitis S, et al. (2008) Respiratory gated diffusion-weighted imaging of the liver: value of apparent diffusion coefficient measurements in the differentiation between most commonly encountered benign and malignant focal liver lesions. Eur Radiol 18:486–492CrossRefGoogle Scholar
  42. 42.
    Wei Y, Gao F, Zheng D, et al. (2018) Intrahepatic cholangiocarcinoma in the setting of HBV-related cirrhosis: Differentiation with hepatocellular carcinoma by using Intravoxel incoherent motion diffusion-weighted MR imaging. Oncotarget 9:7975–7983Google Scholar
  43. 43.
    Fattach HE, Dohan A, Guerrache Y, et al. (2015) Intrahepatic and hilar mass-forming cholangiocarcinoma: Qualitative and quantitative evaluation with diffusion-weighted MR imaging. Eur J Radiol 84:1444–1451CrossRefGoogle Scholar
  44. 44.
    Lee J, Kim SH, Kang TW, Song KD, Choi D, Jang KT (2016) Mass-forming Intrahepatic Cholangiocarcinoma: Diffusion-weighted Imaging as a Preoperative Prognostic Marker. Radiology. 10.1148/radiol.2016151781:151781Google Scholar
  45. 45.
    Kyriazi S, Collins DJ, Messiou C, et al. (2011) Metastatic ovarian and primary peritoneal cancer: assessing chemotherapy response with diffusion-weighted MR imaging–value of histogram analysis of apparent diffusion coefficients. Radiology 261:182–192CrossRefGoogle Scholar
  46. 46.
    Xu XQ, Hu H, Su GY, et al. (2016) Utility of histogram analysis of ADC maps for differentiating orbital tumors. Diagn Interv Radiol 22:161–167CrossRefGoogle Scholar
  47. 47.
    Shindo T, Fukukura Y, Umanodan T, et al. (2016) Histogram Analysis of Apparent Diffusion Coefficient in Differentiating Pancreatic Adenocarcinoma and Neuroendocrine Tumor. Medicine (Baltimore) 95:e2574CrossRefGoogle Scholar
  48. 48.
    Umanodan T, Fukukura Y, Kumagae Y, et al. (2017) ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma. J Magn Reson Imaging 45:1195–1203CrossRefGoogle Scholar
  49. 49.
    Namimoto T, Nakagawa M, Kizaki Y, et al. (2015) Characterization of Liver Tumors by Diffusion-Weighted Imaging: Comparison of Diagnostic Performance Using the Mean and Minimum Apparent Diffusion Coefficient. J Comput Assist Tomogr 39:453–461CrossRefGoogle Scholar
  50. 50.
    O’Connor K, Walsh JC, Schaeffer DF (2014) Combined hepatocellular-cholangiocarcinoma (cHCC-CC): a distinct entity. Ann Hepatol 13:317–322Google Scholar
  51. 51.
    Yeh MM (2010) Pathology of combined hepatocellular-cholangiocarcinoma. J Gastroenterol Hepatol 25:1485–1492CrossRefGoogle Scholar
  52. 52.
    Steens SC, Admiraal-Behloul F, Schaap JA, et al. (2004) Reproducibility of brain ADC histograms. Eur Radiol 14:425–430CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of RadiologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Translational and Molecular Imaging Institute (TMII)Icahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Department of PathologyIcahn School of Medicine at Mount SinaiNew YorkUSA

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