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

  • Hepatobiliary
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Abdominal Radiology Aims and scope Submit manuscript

Abstract

Objective

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].

Methods

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.

Results

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.

Conclusion

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.

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References

  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 72:683–688

    Article  CAS  PubMed  Google Scholar 

  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 61:298–305

    Article  CAS  PubMed  Google Scholar 

  3. Portolani N, Baiocchi GL, Coniglio A, et al. (2008) Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience. Ann Surg Oncol 15:1880–1890

    Article  PubMed  Google Scholar 

  4. Weber SM, Ribero D, O’Reilly EM, et al. (2015) Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford) 17:669–680

    Google Scholar 

  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 201:332–339

    Article  PubMed  Google Scholar 

  6. Jarnagin WR, Weber S, Tickoo SK, et al. (2002) Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer 94:2040–2046

    Article  PubMed  Google Scholar 

  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 45:69–75

    PubMed  Google Scholar 

  8. Dodson RM, Weiss MJ, Cosgrove D, et al. (2013) Intrahepatic cholangiocarcinoma: management options and emerging therapies. J Am Coll Surg 217(736–750):e734

    Google Scholar 

  9. Bruix J, Reig M, Sherman M (2016) Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology 150:835–853

    Article  PubMed  Google Scholar 

  10. Kis B, El-Haddad G, Sheth RA, et al. (2017) Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 24:1073274817729244

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bruix J, Sherman M, American Association for the Study of Liver D (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022

    Article  Google Scholar 

  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 32:1156–1164

    Article  PubMed  Google Scholar 

  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 207:25–31

    Article  PubMed  Google Scholar 

  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 281:150–157

    Article  PubMed  Google Scholar 

  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) 41:2102–2114

    Article  Google Scholar 

  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 38:265–272

    Article  PubMed  Google Scholar 

  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 2:165–173

    Article  CAS  PubMed  Google Scholar 

  18. Chernyak V, Santillan CS, Papadatos D, Sirlin CB (2018) LI-RADS((R)) algorithm: CT and MRI. Abdom Radiol (NY) 43:111–126

    Article  Google Scholar 

  19. Galea N, Cantisani V, Taouli B (2013) Liver lesion detection and characterization: role of diffusion-weighted imaging. J Magn Reson Imaging 37:1260–1276

    Article  PubMed  Google Scholar 

  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 22:373–395

    Article  PubMed  PubMed Central  Google Scholar 

  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 18:477–485

    Article  PubMed  Google Scholar 

  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 246:812–822

    Article  PubMed  Google Scholar 

  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/s00330-017-5156-6

  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:e101944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 19:1302–1309

    Article  PubMed  Google Scholar 

  26. Gillies RJ, Kinahan PE, Hricak H (2016) Radiomics: Images Are More than Pictures, They Are Data. Radiology 278:563–577

    Article  PubMed  Google Scholar 

  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 7:730–735

    Article  PubMed  PubMed Central  Google Scholar 

  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 17:1

    Article  PubMed  PubMed Central  Google Scholar 

  29. Khatri G, Merrick L, Miller FH (2010) MR imaging of hepatocellular carcinoma. Magn Reson Imaging Clin N Am 18(421–450):x

    Google Scholar 

  30. Just N (2014) Improving tumour heterogeneity MRI assessment with histograms. Br J Cancer 111:2205–2213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503

    Article  CAS  PubMed  Google Scholar 

  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:e14–18

    PubMed  Google Scholar 

  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 206:566–572

    Article  PubMed  Google Scholar 

  34. Chung YE, Kim MJ, Park YN, et al. (2009) Varying appearances of cholangiocarcinoma: radiologic-pathologic correlation. Radiographics 29:683–700

    Article  PubMed  Google Scholar 

  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 266:376–382

    Article  PubMed  Google Scholar 

  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) 43:169–178

    Article  Google Scholar 

  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 272:132–142

    Article  PubMed  PubMed Central  Google Scholar 

  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 42:305–314

    Article  PubMed  Google Scholar 

  39. Kim T, Murakami T, Takahashi S, et al. (1999) Diffusion-weighted single-shot echoplanar MR imaging for liver disease. AJR Am J Roentgenol 173:393–398

    Article  CAS  PubMed  Google Scholar 

  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 226:71–78

    Article  PubMed  Google Scholar 

  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 18:486–492

    Article  PubMed  Google Scholar 

  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 9:7975–7983

    PubMed  Google Scholar 

  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 84:1444–1451

    Article  PubMed  Google Scholar 

  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.2016151781:151781

  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 261:182–192

    Article  PubMed  Google Scholar 

  46. Xu XQ, Hu H, Su GY, et al. (2016) Utility of histogram analysis of ADC maps for differentiating orbital tumors. Diagn Interv Radiol 22:161–167

    Article  PubMed  PubMed Central  Google Scholar 

  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:e2574

    Article  CAS  Google Scholar 

  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 45:1195–1203

    Article  PubMed  Google Scholar 

  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 39:453–461

    Article  PubMed  Google Scholar 

  50. O’Connor K, Walsh JC, Schaeffer DF (2014) Combined hepatocellular-cholangiocarcinoma (cHCC-CC): a distinct entity. Ann Hepatol 13:317–322

    Article  Google Scholar 

  51. Yeh MM (2010) Pathology of combined hepatocellular-cholangiocarcinoma. J Gastroenterol Hepatol 25:1485–1492

    Article  PubMed  Google Scholar 

  52. Steens SC, Admiraal-Behloul F, Schaap JA, et al. (2004) Reproducibility of brain ADC histograms. Eur Radiol 14:425–430

    Article  PubMed  Google Scholar 

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Correspondence to Sara Lewis.

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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.

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Lewis, S., Peti, S., Hectors, S.J. et al. Volumetric quantitative histogram analysis using diffusion-weighted magnetic resonance imaging to differentiate HCC from other primary liver cancers. Abdom Radiol 44, 912–922 (2019). https://doi.org/10.1007/s00261-019-01906-7

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