European Radiology

, Volume 28, Issue 5, pp 2047–2057 | Cite as

Prediction of the histopathologic findings of intrahepatic cholangiocarcinoma: qualitative and quantitative assessment of diffusion-weighted imaging

  • Sara LewisEmail author
  • Cecilia Besa
  • Mathilde Wagner
  • Kartik Jhaveri
  • Shingo Kihira
  • Hongfa Zhu
  • Nima Sadoughi
  • Sandra Fischer
  • Amogh Srivastava
  • Eric Yee
  • Koenraad Mortele
  • James Babb
  • Swan Thung
  • Bachir Taouli



To correlate qualitative and quantitative diffusion weighted imaging (DWI) characteristics of intrahepatic cholangiocarcinoma (ICC) with histopathologic tumour grade and fibrosis content.


Fifty-one patients (21M/30F; mean age 61y) with ICC and MRI including DWI were included in this IRB-approved multicentre retrospective study. Qualitative tumour features were assessed. Tumour apparent diffusion coefficient (ADC) mean, minimum, and normalized (nADCliver) values were computed. Tumour grade [well(G1), moderately(G2), or poorly differentiated(G3)] and tumour fibrosis content [minimal(1), moderate(2), or abundant(3)] were categorized pathologically. Imaging findings and ADC values were compared with pathologic measures. Utility of ADC values for predicting tumour grade was assessed using ROC analysis.


51 ICCs (mean size 6.5±1.1 cm) were assessed. 33/51(64%) of ICCs demonstrated diffuse hyperintensity and 15/51(29%) demonstrated target appearance on DWI. Infiltrative morphology (p=0.02) and tumour size (p=0.04) were associated with G3. ADCmean and nADCmean of G3 (1.32±0.47x10-3 mm2/sec and 0.97±0.95) were lower than G1+G2 (1.57±0.39x10-3 mm2/sec and 1.24±0.49; p=0.03 and p=0.04). ADCmean and nADCmean were inversely correlated with tumour grade (p<0.025). No correlation was found between ADC and tumour fibrosis content. AUROC, sensitivity and specificity of nADCmean for G3 versus G1+G2 were 0.71, 89.5% and 55.5%.


ADC quantification has reasonable accuracy for predicting ICC grade.

Key Points

• ADC quantification was useful for predicting ICC tumour grade.

• Infiltrative tumour morphology and size were associated with poorly differentiated ICCs.

• ADC values depended more on ICC tumour grade than fibrosis content.

• Ability to predict ICC tumour grade non-invasively could impact patient management.


Diffusion Magnetic Resonance Imaging Liver Neoplasms Cholangiocarcinoma Tumour Grading Fibrosis 



The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is Sara Lewis, MD.

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

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• diagnostic

• multicentre study

Supplementary material

330_2017_5156_MOESM1_ESM.docx (86 kb)
ESM 1 (DOCX 85 kb)


  1. 1.
    Shaib Y, El-Serag HB (2004) The epidemiology of cholangiocarcinoma. Semin Liver Dis 24:115–125CrossRefPubMedGoogle Scholar
  2. 2.
    Razumilava N, Gores GJ (2014) Cholangiocarcinoma. Lancet 383:2168–2179CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kawarada Y, Yamagiwa K, Das BC (2002) Analysis of the relationships between clinicopathologic factors and survival time in intrahepatic cholangiocarcinoma. Am J Surg 183:679–685CrossRefPubMedGoogle Scholar
  4. 4.
    DeOliveira ML, Cunningham SC, Cameron JL et al (2007) Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 245:755–762CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Konstadoulakis MM, Roayaie S, Gomatos IP et al (2008) Fifteen-year, single-center experience with the surgical management of intrahepatic cholangiocarcinoma: operative results and long-term outcome. Surgery 143:366–374CrossRefPubMedGoogle Scholar
  6. 6.
    Choi SB, Kim KS, Choi JY et al (2009) The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival. Ann Surg Oncol 16:3048–3056CrossRefPubMedGoogle Scholar
  7. 7.
    Saiura A, Yamamoto J, Kokudo N et al (2011) Intrahepatic cholangiocarcinoma: analysis of 44 consecutive resected cases including 5 cases with repeat resections. Am J Surg 201:203–208CrossRefPubMedGoogle Scholar
  8. 8.
    Miura JT, Johnston FM, Tsai S et al (2015) Chemotherapy for Surgically Resected Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 22:3716–3723CrossRefPubMedGoogle Scholar
  9. 9.
    Kajiyama K, Maeda T, Takenaka K, Sugimachi K, Tsuneyoshi M (1999) The significance of stromal desmoplasia in intrahepatic cholangiocarcinoma: a special reference of 'scirrhous-type' and 'nonscirrhous-type' growth. Am J Surg Pathol 23:892–902CrossRefPubMedGoogle Scholar
  10. 10.
    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 246:812–822CrossRefPubMedGoogle Scholar
  11. 11.
    Lewis S, Dyvorne H, Cui Y, Taouli B (2014) Diffusion-weighted imaging of the liver: techniques and applications. Magn Reson Imaging Clin N Am 22:373–395CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Le Bihan D (1991) Molecular diffusion nuclear magnetic resonance imaging. Magn Reson Q 7:1-30Google Scholar
  13. 13.
    Taouli B, Koh DM (2010) Diffusion-weighted MR imaging of the liver. Radiology 254:47–66CrossRefPubMedGoogle Scholar
  14. 14.
    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 19:1302–1309CrossRefPubMedGoogle Scholar
  15. 15.
    Cui XY, Chen HW, Cai S et al (2012) Diffusion-weighted MR imaging for detection of extrahepatic cholangiocarcinoma. Eur J Radiol 81:2961–2965CrossRefPubMedGoogle Scholar
  16. 16.
    Park HJ, Kim YK, Park MJ, Lee WJ (2013) Small intrahepatic mass-forming cholangiocarcinoma: target sign on diffusion-weighted imaging for differentiation from hepatocellular carcinoma. Abdom Imaging 38:793–801CrossRefPubMedGoogle Scholar
  17. 17.
    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 84:1444–1451CrossRefPubMedGoogle Scholar
  18. 18.
    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.
  19. 19.
    Grazioli L, Olivetti L, Fugazzola C et al (1999) The pseudocapsule in hepatocellular carcinoma: correlation between dynamic MR imaging and pathology. Eur Radiol 9:62–67CrossRefPubMedGoogle Scholar
  20. 20.
    Tonan T, Fujimoto K, Qayyum A (2010) Chronic hepatitis and cirrhosis on MR imaging. Magn Reson Imaging Clin N Am 18(383-402):ixGoogle Scholar
  21. 21.
    Tang LH, Berlin J, Branton P et al (2013) Protocol for the Examination of Specimens From Patients With Carcinoma of the Intrahepatic Bile Ducts.Google Scholar
  22. 22.
    Bedossa P, Poynard T (1996) An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 24:289–293Google Scholar
  23. 23.
    Dale BM, Braithwaite AC, Boll DT, Merkle EM (2010) Field strength and diffusion encoding technique affect the apparent diffusion coefficient measurements in diffusion-weighted imaging of the abdomen. Invest Radiol 45:104–108CrossRefPubMedGoogle Scholar
  24. 24.
    Chandarana H, Taouli B (2010) Diffusion and perfusion imaging of the liver. Eur J Radiol 76:348–358CrossRefPubMedGoogle Scholar
  25. 25.
    Huang Z, Xu X, Meng X et al (2015) Correlations between ADC values and molecular markers of Ki-67 and HIF-1alpha in hepatocellular carcinoma. Eur J Radiol 84:2464–2469CrossRefPubMedGoogle Scholar
  26. 26.
    Choi JS, Kim MJ, Choi JY, Park MS, Lim JS, Kim KW (2010) Diffusion-weighted MR imaging of liver on 3.0-Tesla system: effect of intravenous administration of gadoxetic acid disodium. Eur Radiol 20:1052–1060CrossRefPubMedGoogle Scholar
  27. 27.
    Kitis O, Altay H, Calli C, Yunten N, Akalin T, Yurtseven T (2005) Minimum apparent diffusion coefficients in the evaluation of brain tumors. Eur J Radiol 55:393–400CrossRefPubMedGoogle Scholar
  28. 28.
    Lee EJ, Lee SK, Agid R, Bae JM, Keller A, Terbrugge K (2008) Preoperative grading of presumptive low-grade astrocytomas on MR imaging: diagnostic value of minimum apparent diffusion coefficient. AJNR Am J Neuroradiol 29:1872–1877CrossRefPubMedGoogle Scholar
  29. 29.
    Li X, Zhang K, Shi Y, Wang F, Meng X (2016) Correlations between the minimum and mean apparent diffusion coefficient values of hepatocellular carcinoma and tumor grade. J Magn Reson Imaging.
  30. 30.
    Soyer P, Kanematsu M, Taouli B et al (2013) ADC normalization: a promising research track for diffusion-weighted MR imaging of the abdomen. Diagn Interv Imaging 94:571–573CrossRefPubMedGoogle Scholar
  31. 31.
    Do RK, Chandarana H, Felker E et al (2010) Diagnosis of liver fibrosis and cirrhosis with diffusion-weighted imaging: value of normalized apparent diffusion coefficient using the spleen as reference organ. AJR Am J Roentgenol 195:671–676CrossRefPubMedGoogle Scholar
  32. 32.
    Papanikolaou N, Gourtsoyianni S, Yarmenitis S, Maris T, Gourtsoyiannis N (2010) Comparison between two-point and four-point methods for quantification of apparent diffusion coefficient of normal liver parenchyma and focal lesions. Value of normalization with spleen. Eur J Radiol 73:305–309CrossRefPubMedGoogle Scholar
  33. 33.
    Endo I, Gonen M, Yopp AC et al (2008) Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg 248:84–96CrossRefPubMedGoogle Scholar
  34. 34.
    Pascher A, Jonas S, Neuhaus P (2003) Intrahepatic cholangiocarcinoma: indication for transplantation. J Hepatobiliary Pancreat Surg 10:282–287CrossRefPubMedGoogle Scholar
  35. 35.
    Sapisochin G, Rodriguez de Lope C, Gastaca M et al (2014) "Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am J Transplant 14:660–667CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  • Sara Lewis
    • 1
    • 2
    Email author
  • Cecilia Besa
    • 2
    • 3
  • Mathilde Wagner
    • 2
    • 4
  • Kartik Jhaveri
    • 5
  • Shingo Kihira
    • 2
  • Hongfa Zhu
    • 6
  • Nima Sadoughi
    • 5
    • 7
  • Sandra Fischer
    • 8
  • Amogh Srivastava
    • 9
  • Eric Yee
    • 10
    • 11
  • Koenraad Mortele
    • 9
  • James Babb
    • 12
  • Swan Thung
    • 6
  • Bachir Taouli
    • 1
    • 2
  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 RadiologyPontificia Universidad Católica de ChileSantiagoChile
  4. 4.Department of RadiologySorbonne Universités, UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de ParisParisFrance
  5. 5.Department of RadiologyUniversity of TorontoTorontoCanada
  6. 6.Department of PathologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  7. 7.Department of RadiologyUniversity of Ottawa and The Ottawa HospitalOttawaCanada
  8. 8.Department of PathologyUniversity of TorontoOntarioCanada
  9. 9.Department of RadiologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  10. 10.Department of PathologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  11. 11.Department of Pathology, College of MedicineUniversity of Arkansas for Medical SciencesLittle RockUSA
  12. 12.Department of RadiologyNew York University Langone Medical CenterNew YorkUSA

Personalised recommendations