Peri-tumoral hyperintensity on hepatobiliary phase of gadoxetic acid-enhanced MRI in hepatocellular carcinomas: correlation with peri-tumoral hyperplasia and its pathological features

Abdom Radiol (NY). 2018 Aug;43(8):2103-2112. doi: 10.1007/s00261-017-1437-4.


Purpose: Peri-tumoral hyperintensity (P-hyperintensity) is occasionally seen in hepatocellular carcinoma (HCC) on the hepatobiliary (HB) phase of gadoxetic acid-enhanced MRI (EOB-MRI). A recent study reported peri-tumoral hyperplasia (P-hyperplasia) associated with over-expression of glutamine synthetase (GS) in HCC or metastatic carcinoma. The aim of this study was to analyze the correlation between P-hyperintensity on the HB phase and GS expression indicating P-hyperplasia and reveal its pathological features.

Methods: Seventy-seven surgically resected HCCs from 68 patients were analyzed. The grade of P-hyperintensity on HB phase was divided according to the degree of the peri-tumoral hyperintense signal: grade 0 (no P-hyperintensity), grade 1 (less than 50% of the tumor border), grade 2 (50%-80%), grade 3 (80%-100%). Immunohistochemical staining for GS and organic anion transporter polypeptides (OATP)1B3 was performed. The relationships among P-hyperplasia (peri-tumoral GS expression) and OATP1B3 expression, P-hyperintensity, and pathological features of the tumor were analyzed.

Results: Thirty-four HCCs were classified as P-hyperintensity grade 0, 29 HCCs as grade 1,10 nodules as grade 2, and 4 HCCs as grade 3. P-hyperplasia was observed in 3/34 (8.8%) P-hyperintensity grade 0, 16/29 (55.2%) grade 1, 9/10 (90%) grade 2, and 4/4 (100%) grade 3. The incidence of P-hyperplasia was significantly increased in P-hyperintensity grades 1-3 compared with grade 0 (p < 0.0001). Hepatocytes in all P-hyperplasia sites demonstrated definite OATP1B3 expression. Microscopic hepatic venous invasion was significantly increased in P-hyperintensity-positive HCCs compared with negative HCCs (p = 0.0017).

Conclusions: P-hyperintensity on HB phase in HCC may indicate p-hyperplasia with GS and OATP1B3 expression and a higher incidence of microscopic hepatic venous invasion.

Keywords: EOB; Gadoxetic acid; HCC; OATP1B3; Peri-tumoral hyperintensity; Peri-tumoral hyperplasia.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Carcinoma, Hepatocellular / pathology
  • Contrast Media*
  • Female
  • Gadolinium DTPA*
  • Humans
  • Hyperplasia
  • Image Enhancement / methods*
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Retrospective Studies


  • Contrast Media
  • gadolinium ethoxybenzyl DTPA
  • Gadolinium DTPA