Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging--correlation with molecular transporters and histopathologic features

Radiology. 2010 Sep;256(3):817-26. doi: 10.1148/radiol.10092214. Epub 2010 Jul 27.


Purpose: To analyze the correlation between signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging and the expression of hepatocyte transporters with histopathologic features in hepatocellular carcinoma (HCC).

Materials and methods: Institutional ethics committee approval and informed consent were obtained. Forty surgically resected HCCs were classified as hypointense (n = 32) or iso- or hyperintense (n = 8) on the basis of findings in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging. The following were compared between hypointense and iso- or hyperintense HCCs: the time-signal intensity curves at gadoxetic acid-enhanced MR imaging, the expression levels of seven transporters (four organic anion-transporting polypeptides [OATPs] and three multidrug-resistant proteins [MRPs]) at polymerase chain reaction (PCR) (for 22 nodules), results of immunostaining of OATP8, and histologic features. Statistical analysis (unpaired t test, Mann-Whitney test, chi(2) test, and Fisher exact test) was performed for each result.

Results: On the time-signal intensity curves, hypointense HCCs showed a decreasing pattern, whereas iso- or hyperintense HCCs showed an increasing pattern after the dynamic phase. PCR revealed that expression of OATP8 (an uptake transporter) in hypointense HCCs was lower and that in iso- or hyperintense HCCs was higher than in background liver (P < .001). The expression level of MRP3 (a sinusoidal export transporter) showed a similar trend to that of OATP8 (P < .001). Immunostaining revealed that OATP8 expression was weak in hypointense HCCs, whereas it was sustained in iso- or hyperintense HCCs (P < .001). At histologic examination, a pseudoglandular proliferation pattern with bile plugs was more commonly observed in iso- or hyperintense HCCs than in hypointense HCCs (P = .01 for proliferation patterns and P = .006 for bile plugs).

Conclusion: The enhancement ratio of HCCs in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging positively correlated with expression levels of OATP8 and MRP3, indicating that gadoxetic acid is taken up by OATP8 and excreted by MRP3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Chi-Square Distribution
  • Contrast Media / pharmacokinetics*
  • Female
  • Gadolinium DTPA / pharmacokinetics*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • RNA, Messenger / metabolism
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Statistics, Nonparametric


  • Contrast Media
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters, Sodium-Independent
  • RNA, Messenger
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • gadolinium ethoxybenzyl DTPA
  • multidrug resistance-associated protein 3
  • Gadolinium DTPA