European Radiology

, Volume 29, Issue 10, pp 5205–5216 | Cite as

Detection of liver metastases on gadobenate dimeglumine-enhanced MRI: systematic review, meta-analysis, and similarities with gadoxetate-enhanced MRI

  • Ling Zhang
  • Xian Yu
  • Lei Huo
  • Lun Lu
  • Xinpeng Pan
  • Ningyang JiaEmail author
  • Xinxiang FanEmail author
  • Giovanni Morana
  • Luigi Grazioli
  • Guenther Schneider
Contrast Media



To determine the sensitivity and positive predictive value (PPV) of gadobenate-enhanced MR imaging for the detection of liver metastases.


This systematic review and meta-analysis was conducted according to PRISMA guidelines. A comprehensive search (EMBASE, PubMed) was performed to identify relevant articles up to December 2017. Studies eligible for inclusion were performed using appropriate methodology with complete verification by means of histopathology, intraoperative observation and/or follow-up, and sufficient information to permit determination of true-positive (TP), false-negative (FN), and false-positive (FP) values. Sources of bias were assessed using the QUADAS-2 tool. An inverse variance-weighted random-effects model was used to obtain sensitivity and PPV estimates. Information was analyzed and presented using Cochran’s Q statistic, funnel plots, and modified Deeks’ analysis.


Ten articles (256 patients, 562 metastases) were included. Sensitivity estimates for pre-contrast (unenhanced) imaging, gadobenate-enhanced dynamic imaging, and combined unenhanced, dynamic, and delayed hepatobiliary phase imaging for detecting liver metastases on a per-lesion basis were 77.8% (95% CI 71.4–84.3%, 7 assessments), 88.1% (95% CI, 84.0–92.2%, 13 assessments), and 95.1% (95% CI 93.1–97.1%, 15 assessments), respectively. The addition of hepatobiliary phase images significantly improved the detection of liver metastases. The overall PPV was 90.9% (95% CI 86.6–95.1%, 11 assessments). Deeks’ funnel analysis revealed no association between sample size and sensitivity (β = 0.02, p = 0.814) indicating no significant publication bias.


Gadobenate-enhanced MR imaging has high sensitivity and PPV for the detection of liver metastases on a per-lesion basis. The sensitivity and PPV for detection is comparable to reported values for the pure liver-specific agent gadoxetate.

Key Points

• Gadobenate dimeglumine is a hepatobiliary MR contrast agent that permits acquisition of contrast-enhanced liver images during the immediate post-injection dynamic phase, like any extracellular agent, and in the delayed hepatobiliary phase, after specific uptake by the hepatocytes.

• The hepatobiliary phase improves detection of liver metastases when compared either to pre-contrast unenhanced images alone or to pre-contrast + gadobenate-enhanced dynamic phase images.

• The meta-analysis showed an overall sensitivity of 95.1% and PPV of 90.9% of gadobenate-enhanced MRI for the detection of metastases, when based on the evaluation of all available acquisitions.


Gadobenate dimeglumine (MultiHance) Liver MRI Liver metastases Meta-analysis 



Confidence interval


Diffusion-weighted imaging


False negative


False positive


Gadolinium-based contrast agent


Intraoperative ultrasound


Magnetic resonance imaging


Neoadjuvant chemotherapy


Positron emission tomography/computerized tomography


Positive predictive value


Preferred reporting items for systematic reviews and meta-analyses


Quality assessment of diagnostic accuracy studies


True positive



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

Compliance with ethical standards


The scientific guarantor of this publication is Hongyan Chen.

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 not required for this study because it is a meta-analysis on published literature.

Ethical approval

Institutional Review Board approval was not required because it is a meta-analysis on published literature.


• retrospective

• diagnostic study

• performed at one institution


  1. 1.
    Lincke T, Zech CJ (2017) Liver metastases: detection and staging. Eur J Radiol 97:76–82CrossRefPubMedGoogle Scholar
  2. 2.
    Kaur H, Hindman NM, Al-Refaie WB et al (2017) ACR Appropriateness Criteria® suspected liver metastases. J Am Coll Radiol 14(5S):S314–S325CrossRefPubMedGoogle Scholar
  3. 3.
    Asato N, Tsurusaki M, Sofue K et al (2017) Comparison of gadoxetic acid-enhanced dynamic MR imaging and contrast-enhanced computed tomography for preoperative evaluation of colorectal liver metastases. Jpn J Radiol 35:197–205CrossRefPubMedGoogle Scholar
  4. 4.
    Jhaveri KS, Fischer SE, Hosseini-Nik H et al (2017) Prospective comparison of gadoxetic acid-enhanced liver MRI and contrast-enhanced CT with histopathological correlation for preoperative detection of colorectal liver metastases following chemotherapy and potential impact on surgical plan. HPB (Oxford) 19:992–1000CrossRefGoogle Scholar
  5. 5.
    Schulz A, Viktil E, Godt JC et al (2016) Diagnostic performance of CT, MRI and PET/CT in patients with suspected colorectal liver metastases: the superiority of MRI. Acta Radiol 57:1040–1048CrossRefPubMedGoogle Scholar
  6. 6.
    Hänle MM, Thiel R, Saur G, Mason RA, Pauls S, Kratzer W (2011) Screening for liver metastases in women with mammary carcinoma: comparison of contrast-enhanced ultrasound and magnetic resonance imaging. Clin Imaging 35:366–370CrossRefPubMedGoogle Scholar
  7. 7.
    Primovist European Package Insert. Available at: Accessed 10 Feb 2018
  8. 8.
    MultiHance European Package Insert. Available at: Accessed 10 Feb 2018
  9. 9.
    Morana G, Grazioli L, Testoni M, Caccia P, Procacci C (2002) Contrast agents for hepatic magnetic resonance imaging. Top Magn Reson Imaging 13:117–150CrossRefPubMedGoogle Scholar
  10. 10.
    Seale MK, Catalano OA, Saini S, Hahn PF, Sahani DV (2009) Hepatobiliary-specific MR contrast agents: role in imaging the liver and biliary tree. Radiographics. 29:1725–1748CrossRefPubMedGoogle Scholar
  11. 11.
    Goodwin MD, Dobson JE, Sirlin CB, Lim BG, Stella DL (2011) Diagnostic challenges and pitfalls in MR imaging with hepatocyte-specific contrast agents. Radiographics. 31:1547–1568CrossRefPubMedGoogle Scholar
  12. 12.
    Feuerlein S, Gupta RT, Boll DT, Merkle EM (2012) Hepatocellular MR contrast agents: enhancement characteristics of liver parenchyma and portal vein after administration of gadoxetic acid in comparison to gadobenate dimeglumine. Eur J Radiol 81:2037–2041CrossRefPubMedGoogle Scholar
  13. 13.
    Hope TA, Fowler KJ, Sirlin CB et al (2015) Hepatobiliary agents and their role in LI-RADS. Abdom Imaging 40:613–625CrossRefPubMedGoogle Scholar
  14. 14.
    MultiHance U.S. Package Insert. Available at:,021358s013lbl.pdf. Accessed 10 Feb 2018
  15. 15.
    Chen L, Zhang J, Zhang L et al (2012) Meta-analysis of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging for the detection of liver metastases. PLoS One 7:e48681CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Vilgrain V, Esvan M, Ronot M, Caumont-Prim A, Aubé C, Chatellier G (2016) A meta-analysis of diffusion-weighted and gadoxetic acid-enhanced MR imaging for the detection of liver metastases. Eur Radiol 26:4595–4515CrossRefGoogle Scholar
  17. 17.
    Vreugdenburg TD, Ma N, Duncan JK, Riitano D, Cameron AL, Maddern GJ (2016) Comparative diagnostic accuracy of hepatocyte-specific gadoxetic acid (Gd-EOB-DTPA) enhanced MR imaging and contrast enhanced CT for the detection of liver metastases: a systematic review and meta-analysis. Int J Colorectal Dis 31:1739–1749CrossRefPubMedGoogle Scholar
  18. 18.
    Choi SH, Kim SY, Park SH et al (2018) Diagnostic performance of CT, gadoxetate disodium-enhanced MRI, and PET/CT for the diagnosis of colorectal liver metastasis: systematic review and meta-analysis. J Magn Reson Imaging 47:1237–1250CrossRefPubMedGoogle Scholar
  19. 19.
    Neri E, Bali MA, Ba-Ssalamah A et al (2016) ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents. Eur Radiol 26:921–931CrossRefPubMedGoogle Scholar
  20. 20.
    Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Whiting PF, Rutjes AW, Westwood ME et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F (2000) Methods for meta-analysis in medical research. Wiley, New YorkGoogle Scholar
  23. 23.
    Borenstein M, Hedges LV, Higgins JPT, Rothstein H (2009) Introduction to meta-analysis, 1st edn. Wiley, West SussexGoogle Scholar
  24. 24.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefGoogle Scholar
  25. 25.
    Higgins JP, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analysis. BMJ. 327(7414):557–560CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58:882–893CrossRefGoogle Scholar
  27. 27.
    van Enst WA, Ochodo E, Scholten RJ, Hooft L, Leeflang MM (2014) Investigation of publication bias in meta-analysis of diagnostic test accuracy: a meta-epidemiological study. BMC Med Res Methodol 14:70Google Scholar
  28. 28.
    Pirovano G, Vanzulli A, Marti-Bonmati L et al (2000) Evaluation of the accuracy of gadobenate dimeglumine-enhanced MR imaging in the detection and characterization of focal liver lesions. AJR Am J Roentgenol 175:1111–1120CrossRefPubMedGoogle Scholar
  29. 29.
    del Frate C, Bazzocchi M, Mortele KJ et al (2002) Detection of liver metastases: comparison of gadobenate dimeglumine-enhanced and ferumoxides-enhanced MR imaging examinations. Radiology. 225:766–772CrossRefPubMedGoogle Scholar
  30. 30.
    Kim YK, Lee JM, Kim CS (2004) Gadobenate dimeglumine-enhanced liver MR imaging: value of dynamic and delayed imaging for the characterization and detection of focal liver lesions. Eur Radiol 14:5–13CrossRefPubMedGoogle Scholar
  31. 31.
    Kim YK, Lee JM, Kim CS, Chung GH, Kim CY, Kim IH (2005) Detection of liver metastases: gadobenate dimeglumine-enhanced three-dimensional dynamic phases and one-hour delayed phase MR imaging versus superparamagnetic iron oxide-enhanced MR imaging. Eur Radiol 15:220–228CrossRefPubMedGoogle Scholar
  32. 32.
    Lee HY, Lee JM, Kim SH et al (2008) Detection and characterization of focal hepatic lesions: comparative study of MDCT and gadobenate dimeglumine-enhanced MR imaging. Clin Imaging 32:287–295CrossRefPubMedGoogle Scholar
  33. 33.
    Baek SE, Park MS, Hong HS et al (2010) Characterisation of small hypoattenuating hepatic lesions in multi-detector CT (MDCT) in patients with underlying extrahepatic malignancy: added value of contrast-enhanced MR images. Eur Radiol 20:2853–2861CrossRefPubMedGoogle Scholar
  34. 34.
    Choi JY, Choi JS, Kim MJ et al (2010) Detection of hepatic hypovascular metastases: 3D gradient echo MRI using a hepatobiliary contrast agent. J Magn Reson Imaging 31:571–578CrossRefPubMedGoogle Scholar
  35. 35.
    Hekimoglu K, Ustundag Y, Dusak A et al (2011) Small colorectal liver metastases: detection with SPIO-enhanced MRI in comparison with gadobenate dimeglumine-enhanced MRI and CT imaging. Eur J Radiol 77:468–472CrossRefPubMedGoogle Scholar
  36. 36.
    Morana G, Grazioli L, Kirchin MA et al (2011) Solid hypervascular liver lesions: accurate identification of true benign lesions on enhanced dynamic and hepatobiliary phase magnetic resonance imaging after gadobenate dimeglumine administration. Invest Radiol 46:225–239CrossRefPubMedGoogle Scholar
  37. 37.
    Brismar TB, Kartalis N, Kylander C, Albiin N (2012) MRI of colorectal cancer liver metastases: comparison of orally administered manganese with intravenously administered gadobenate dimeglumine. Eur Radiol 22:633–641CrossRefPubMedGoogle Scholar
  38. 38.
    Hardie AD, Naik M, Hecht EM et al (2010) Diagnosis of liver metastases: value of diffusion-weighted MRI compared with gadolinium-enhanced MRI. Eur Radiol 20:1431–1441CrossRefPubMedGoogle Scholar
  39. 39.
    Ueda K, Matsui O, Nobata K, Takashima T (1996) Mucinous carcinoma of the liver mimicking cavernous hemangioma on pre- and postcontrast MR imaging. AJR Am J Roentgenol 166:468–469CrossRefPubMedGoogle Scholar
  40. 40.
    Kanematsu M, Kondo H, Goshima S et al (2006) Imaging liver metastases: review and update. Eur J Radiol 58:217–228CrossRefPubMedGoogle Scholar
  41. 41.
    Lacout A, El Hajjam M, Julie C, Lacombe P, Pelage JP (2008) Liver metastasis of a mucinous colonic carcinoma mimicking a haemangioma in T2-weighted sequences. J Med Imaging Radiat Oncol 52:580–582CrossRefPubMedGoogle Scholar
  42. 42.
    McFarland EG, Mayo-Smith WW, Saini S, Hahn PF, Goldberg MA, Lee MJ (1994) Hepatic hemangiomas and malignant tumors: improved differentiation with heavily T2-weighted conventional spin-echo MR imaging. Radiology 193:43–47CrossRefPubMedGoogle Scholar
  43. 43.
    Ito K, Mitchell D, Outwater E, Szklaruk J, Sadek A (1997) Hepatic lesions: discrimination of nonsolid, benign lesions from solid, malignant lesions with heavily T2-weighted fast spin-echo MR imaging. Radiology 204:729–737CrossRefPubMedGoogle Scholar
  44. 44.
    Scharitzer M, Ba-Ssalamah A, Ringl H et al (2013) Preoperative evaluation of colorectal liver metastases: comparison between gadoxetic acid-enhanced 3.0-T MRI and contrast-enhanced MDCT with histopathological correlation. Eur Radiol 23:2187–2196CrossRefPubMedGoogle Scholar
  45. 45.
    Berger-Kulemann V, Schima W, Baroud S et al (2012) Gadoxetic acid-enhanced 3.0 T MR imaging versus multidetector-row CT in the detection of colorectal metastases in fatty liver using intraoperative ultrasound and histopathology as a standard of reference. Eur J Surg Oncol 38:670–676CrossRefPubMedGoogle Scholar
  46. 46.
    Sofue K, Tsurusaki M, Tokue H, Arai Y, Sugimura K (2011) Gd-EOB-DTPA-enhanced 3.0 T MR imaging: quantitative and qualitative comparison of hepatocyte-phase images obtained 10 min and 20 min after injection for the detection of liver metastases from colorectal carcinoma. Eur Radiol 21:2336–2343CrossRefPubMedGoogle Scholar
  47. 47.
    Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC intergroup trial 40983): a randomised controlled trial. Lancet 371:1007–1016CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Goéré D, Elias D (2008) Resection of liver metastases from noncolorectal non-endocrine primary tumours. Eur J Surg Oncol 34:281–288CrossRefPubMedGoogle Scholar
  49. 49.
    Grazioli L, Morana G, Caudana R et al (2000) Hepatocellular carcinoma: correlation between gadobenate dimeglumine-enhanced MRI and pathologic findings. Invest Radiol 35:25–34CrossRefPubMedGoogle Scholar
  50. 50.
    Grazioli L, Morana G, Federle MP et al (2001) Focal nodular hyperplasia: morphologic and functional information from MR imaging with gadobenate dimeglumine. Radiology. 221:731–739CrossRefPubMedGoogle Scholar
  51. 51.
    Grazioli L, Morana G, Kirchin MA, Schneider G (2005) Accurate differentiation of focal nodular hyperplasia from hepatic adenoma at gadobenate dimeglumine-enhanced MR imaging: prospective study. Radiology. 236:166–177CrossRefPubMedGoogle Scholar
  52. 52.
    Fu GL, Du Y, Zee CS et al (2012) Gadobenate dimeglumine-enhanced liver magnetic resonance imaging: value of hepatobiliary phase for the detection of focal liver lesions. J Comput Assist Tomogr 36:14–19Google Scholar
  53. 53.
    Mürtz P, Sprinkart AM, Reick M et al (2018) Accurate IVIM model-based liver lesion characterisation can be achieved with only three b-value DWI. Eur Radiol 28(10):4418–4428CrossRefPubMedGoogle Scholar
  54. 54.
    Schneider G, Altmeyer K, Kirchin MA et al (2007) Evaluation of a novel time-efficient protocol for gadobenate dimeglumine (Gd-BOPTA)-enhanced liver magnetic resonance imaging. Invest Radiol 42:105–115CrossRefPubMedGoogle Scholar
  55. 55.
    Sivesgaard K, Larsen LP, Sørensen M et al (2018) Diagnostic accuracy of CE-CT, MRI and FDG PET/CT for detecting colorectal cancer liver metastases in patients considered eligible for hepatic resection and/or local ablation. Eur Radiol.
  56. 56.
    van Kessel CS, Buckens CF, van den Bosch MA, van Leeuwen MS, van Hillegersberg R, Verkooijen HM (2012) Preoperative imaging of colorectal liver metastases after neoadjuvant chemotherapy: a meta-analysis. Ann Surg Oncol 19:2805–2813CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  • Ling Zhang
    • 1
  • Xian Yu
    • 2
  • Lei Huo
    • 3
  • Lun Lu
    • 3
  • Xinpeng Pan
    • 3
  • Ningyang Jia
    • 3
    Email author
  • Xinxiang Fan
    • 4
    Email author
  • Giovanni Morana
    • 5
  • Luigi Grazioli
    • 6
  • Guenther Schneider
    • 7
  1. 1.Department of Radiology, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Department of gastrointestinal surgeryChongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer HospitalChongqingChina
  3. 3.Department of Radiology, Shanghai Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina
  4. 4.Department of Urology, Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina
  5. 5.Department of RadiologyOspedale Ca’ FoncelloTrevisoItaly
  6. 6.Department of RadiologyUniversity of Brescia, Ospedale “Spedali Civili”BresciaItaly
  7. 7.Department of RadiologySaarland University Medical CenterHomburgGermany

Personalised recommendations