Detection of liver metastases on gadobenate dimeglumine-enhanced MRI: systematic review, meta-analysis, and similarities with gadoxetate-enhanced MRI
- 268 Downloads
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.
• 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.
KeywordsGadobenate dimeglumine (MultiHance) Liver MRI Liver metastases Meta-analysis
Gadolinium-based contrast agent
Magnetic resonance imaging
Positron emission tomography/computerized tomography
Positive predictive value
Preferred reporting items for systematic reviews and meta-analyses
Quality assessment of diagnostic accuracy studies
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.
Written informed consent was not required for this study because it is a meta-analysis on published literature.
Institutional Review Board approval was not required because it is a meta-analysis on published literature.
• diagnostic study
• performed at one institution
- 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
- 7.Primovist European Package Insert. Available at: https://www.medicines.org.uk/emc/medicine/15927. Accessed 10 Feb 2018
- 8.MultiHance European Package Insert. Available at: www.medicines.org.uk/emc/medicine/6132. Accessed 10 Feb 2018
- 14.MultiHance U.S. Package Insert. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2018/021357s014,021358s013lbl.pdf. Accessed 10 Feb 2018
- 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
- 22.Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F (2000) Methods for meta-analysis in medical research. Wiley, New YorkGoogle Scholar
- 23.Borenstein M, Hedges LV, Higgins JPT, Rothstein H (2009) Introduction to meta-analysis, 1st edn. Wiley, West SussexGoogle Scholar
- 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
- 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.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.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
- 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
- 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. https://doi.org/10.1007/s00330-018-5469-0