Combined gadoxetic acid and gadobenate dimeglumine enhanced liver MRI: a parameter optimization study

  • Gesine Knobloch
  • Timothy Colgan
  • Xiaoke Wang
  • Kaitlin M. Woo
  • Tilman Schubert
  • Scott B. ReederEmail author



To demonstrate the feasibility of combined delayed-phase gadoxetic acid (GA) and gadobenate dimeglumine (GD) enhanced liver MRI for improved detection of liver metastases, and to optimize contrast agent dose, timing, and flip angle (FA).


Fourteen healthy volunteers underwent liver MRI at 3.0T at two visits during which they received two consecutive injections: 1. GA (Visit 1 = 0.025 mmol/kg; Visit 2 = 0.05 mmol/kg) and 2. GD (both visits = 0.1 mmol/kg) 20 min after GA administration. Two sub-studies were performed: Experiment-1 Eight subjects underwent multi-phase breath-held 3D-fat-saturated T1-weighted spoiled gradient echo (SGRE) imaging to determine the optimal imaging window for the combined GA + GD protocol to create a homogeneously hyperintense liver and vasculature (“plain-white-liver”) with maximum contrast to muscle which served as a surrogate for metastatic lesions in both experiments. Experiment-2 Six subjects underwent breath-held 3D-fat-saturated T1-weighted SGRE imaging at three different FA to determine the optimal FA for best image contrast. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated.


Experiment-1 The combined GA + GD protocol created a homogeneously hyperintense liver and vasculature with maximum CNR liver/muscle at approximately 60–120 s after automatic GD-bolus detection. Experiment-2 Flip angles between 25° and 35° at a dose of 0.025 mmol/kg GA provided the best combination that minimized liver/vasculature CNR, while maximizing liver/muscle CNR. CNR performance to achieve a “plain-white-liver” was superior with 0.025 mmol/kg GA compared to 0.05 mmol/kg.


Combined GA + GD enhanced T1-weighted MRI is feasible to achieve a homogeneously “plain-white-liver”. Future studies need to confirm that this protocol can improve sensitivity of liver lesion detection in patients with metastatic liver disease.


Gadolinium ethoxybenzyl DTPA Gadobenic acid Contrast media Magnetic resonance imaging Liver diseases 



The authors thank Jenelle Fuller, Kelli Hellenbrand, and Sara John for their assistance in the recruitment and imaging of the volunteers. The authors gratefully acknowledge support from the NIH (K24 DK102595) and the Departments of Radiology and Medical Physics at the University of Wisconsin. We also wish to acknowledge GE Healthcare and Bracco Diagnostics who provided research support to the University of Wisconsin. Further, Dr. Reeder is a Romnes Faculty Fellow, and has received an award provided by the University of Wisconsin-Madison Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation.

Compliance with ethical standards


Scott Reeder is a shareholder of Reveal Pharmaceuticals. No authors have any other potential conflicts of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of RadiologyUniversity of Wisconsin – School of Medicine and Public HealthMadisonUSA
  2. 2.Department of Biomedical EngineeringUniversity of Wisconsin – School of Medicine and Public HealthMadisonUSA
  3. 3.Department of Biostatistics and Medical InformaticsUniversity of Wisconsin – School of Medicine and Public HealthMadisonUSA
  4. 4.Clinic for Radiology and Nuclear MedicineBasel University HospitalBaselSwitzerland
  5. 5.Department of Medical PhysicsUniversity of Wisconsin – School of Medicine and Public HealthMadisonUSA
  6. 6.Department of MedicineUniversity of Wisconsin – School of Medicine and Public HealthMadisonUSA
  7. 7.Department of Emergency MedicineUniversity of Wisconsin – School of Medicine and Public HealthMadisonUSA

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