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

  • Hepatobiliary
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusion

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.

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References

  1. FDA. EOVIST (Gadoxetate Disodium) Labeling-Package Insert 2008. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=022090. Accessed 2018.

  2. Theilig D, Elkilany A, Schmelzle M, Muller T, Hamm B, Denecke T. Consistency of hepatocellular gadoxetic acid uptake in serial MRI examinations for evaluation of liver function. 2019.

  3. Kukuk GM, Schaefer SG, Fimmers R, et al. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests. Eur Radiol. 2014;24(10):2482-90.

    Article  PubMed  Google Scholar 

  4. Ba-Ssalamah A, Qayyum A, Bastati N, Fakhrai N, Herold CJ, Caseiro Alves F. P4 radiology of hepatobiliary diseases with gadoxetic acid-enhanced MRI as a biomarker. Expert review of gastroenterology & hepatology. 2014;8(2):147-60.

  5. Hamm B, Staks T, Muhler A, et al. Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology. 1995;195(3):785-92.

    Article  CAS  PubMed  Google Scholar 

  6. Bluemke DA, Sahani D, Amendola M, et al. Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study. Radiology. 2005;237(1):89-98.

    Article  PubMed  Google Scholar 

  7. Frydrychowicz A, Lubner MG, Brown JJ, et al. Hepatobiliary MR imaging with gadolinium-based contrast agents. Journal of magnetic resonance imaging : JMRI. 2012;35(3):492-511.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chen BB, Hsu CY, Yu CW, et al. Clinical and histologic implications of delayed hepatobiliary enhancement on magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic Acid. Invest Radiol. 2012;47(11):649-55.

    Article  CAS  PubMed  Google Scholar 

  9. Hammerstingl R, Huppertz A, Breuer J, et al. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions. Eur Radiol. 2008;18(3):457-67.

    Article  PubMed  Google Scholar 

  10. Huppertz A, Balzer T, Blakeborough A, et al. Improved detection of focal liver lesions at MR imaging: multicenter comparison of gadoxetic acid-enhanced MR images with intraoperative findings. Radiology. 2004;230(1):266-75.

    Article  PubMed  Google Scholar 

  11. Motosugi U, Ichikawa T, Morisaka H, et al. Detection of pancreatic carcinoma and liver metastases with gadoxetic acid-enhanced MR imaging: comparison with contrast-enhanced multi-detector row CT. Radiology. 2011;260(2):446-53.

    Article  PubMed  Google Scholar 

  12. Muhi A, Ichikawa T, Motosugi U, et al. Diagnosis of colorectal hepatic metastases: comparison of contrast-enhanced CT, contrast-enhanced US, superparamagnetic iron oxide-enhanced MRI, and gadoxetic acid-enhanced MRI. Journal of magnetic resonance imaging : JMRI. 2011;34(2):326-35.

    Article  PubMed  Google Scholar 

  13. Kim JH, Lee SJ, Moon SH, et al. Incremental value of cell block preparations over conventional smears alone in the evaluation of EUS-FNA for pancreatic masses. Hepato-gastroenterology. 2014;61(135):2117-22.

  14. Motosugi U, Ichikawa T, Onohara K, et al. Distinguishing hepatic metastasis from hemangioma using gadoxetic acid-enhanced magnetic resonance imaging. Invest Radiol. 2011;46(6):359-65.

    Article  PubMed  Google Scholar 

  15. Goshima S, Kanematsu M, Watanabe H, et al. Hepatic hemangioma and metastasis: differentiation with gadoxetate disodium-enhanced 3-T MRI. AJR American journal of roentgenology. 2010;195(4):941-6.

    Article  PubMed  Google Scholar 

  16. Heiken JP. Distinguishing benign from malignant liver tumours. Cancer imaging : the official publication of the International Cancer Imaging Society. 2007;7 Spec No A:S1-14.

  17. Doo KW, Lee CH, Choi JW, Lee J, Kim KA, Park CM. “Pseudo washout” sign in high-flow hepatic hemangioma on gadoxetic acid contrast-enhanced MRI mimicking hypervascular tumor. AJR American journal of roentgenology. 2009;193(6):W490-6.

    Article  PubMed  Google Scholar 

  18. Ba-Ssalamah A, Uffmann M, Saini S, Bastati N, Herold C, Schima W. Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions. Eur Radiol. 2009;19(2):342-57.

    Article  PubMed  Google Scholar 

  19. Well L, Rausch VH, Adam G, Henes FO, Bannas P. Transient Severe Motion Artifact Related to Gadoxetate Disodium-Enhanced Liver MRI: Frequency and Risk Evaluation at a German Institution. Rofo. 2017;189(7):651-60.

    Article  Google Scholar 

  20. Motosugi U, Bannas P, Bookwalter CA, Sano K, Reeder SB. An Investigation of Transient Severe Motion Related to Gadoxetic Acid-enhanced MR Imaging. Radiology. 2016;279(1):93-102.

    Article  PubMed  Google Scholar 

  21. Davenport MS, Viglianti BL, Al-Hawary MM, et al. Comparison of acute transient dyspnea after intravenous administration of gadoxetate disodium and gadobenate dimeglumine: effect on arterial phase image quality. Radiology. 2013;266(2):452-61.

    Article  PubMed  Google Scholar 

  22. McClellan TR, Motosugi U, Middleton MS, et al. Intravenous Gadoxetate Disodium Administration Reduces Breath-holding Capacity in the Hepatic Arterial Phase: A Multi-Center Randomized Placebo-controlled Trial. Radiology. 2017;282(2):361-8.

    Article  PubMed  Google Scholar 

  23. Bannas P, Motosugi U, Hernando D, Rahimi MS, Holmes JH, Reeder SB. Combined gadoxetic acid and gadofosveset enhanced liver MRI: A feasibility and parameter optimization study. Magn Reson Med. 2016;75(1):318-28.

    Article  PubMed  CAS  Google Scholar 

  24. Bannas P, Bookwalter CA, Ziemlewicz T, et al. Combined gadoxetic acid and gadofosveset enhanced liver MRI for detection and characterization of liver metastases. Eur Radiol. 2017;27(1):32-40.

    Article  PubMed  PubMed Central  Google Scholar 

  25. FDA. ABLAVAR (gadofosveset trisodium) Labeling-Package Insert 2013; vol 2018, no Jan 28, 2018. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=021711.

  26. FDA. Gadavist (gadobutrol) Labeling-Package Insert 2011; vol 2018, no Jan 28, 2018. Available at: https://google2.fda.gov/search?q=gadavist&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&requiredfields=-archive%3AYes&output=xml_no_dtd&getfields=*.

  27. FDA. MultiHance (gadobenate dimeglumine) Labeling-Package Insert 2018; vol 2018, no Jan 28, 2018. Available at: https://google2.fda.gov/search?q=multihance&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&requiredfields=-archive%3AYes&output=xml_no_dtd&getfields=*.

  28. FDA. DOTAREM® (gadoterate meglumine) Labeling-Package Insert 2017; vol 2018, no Jan 28,2018. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=204781.

  29. Motosugi U, Ichikawa T, Sano K, et al. Double-dose gadoxetic Acid-enhanced magnetic resonance imaging in patients with chronic liver disease. Invest Radiol. 2011;46(2):141-5.

    Article  CAS  PubMed  Google Scholar 

  30. Nagle SK, Busse RF, Brau AC, et al. High resolution navigated three-dimensional T(1)-weighted hepatobiliary MRI using gadoxetic acid optimized for 1.5 Tesla. Journal of magnetic resonance imaging : JMRI. 2012;36(4):890-9.

    Article  PubMed  Google Scholar 

  31. Frydrychowicz A, Nagle SK, D’Souza SL, Vigen KK, Reeder SB. Optimized high-resolution contrast-enhanced hepatobiliary imaging at 3 tesla: a cross-over comparison of gadobenate dimeglumine and gadoxetic acid. Journal of magnetic resonance imaging : JMRI. 2011;34(3):585-94.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Runge VM. A comparison of two MR hepatobiliary gadolinium chelates: Gd-BOPTA and Gd-EOB-DTPA. Journal of computer assisted tomography. 1998;22(4):643-50.

    Article  CAS  PubMed  Google Scholar 

  33. Brau AC, Beatty PJ, Skare S, Bammer R. Comparison of reconstruction accuracy and efficiency among autocalibrating data-driven parallel imaging methods. Magn Reson Med. 2008;59(2):382-95.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Reeder SB, Wintersperger BJ, Dietrich O, et al. Practical approaches to the evaluation of signal-to-noise ratio performance with parallel imaging: application with cardiac imaging and a 32-channel cardiac coil. Magn Reson Med. 2005;54(3):748-54.

    Article  PubMed  Google Scholar 

  35. Edelstein WA, Bottomley PA, Hart HR, Smith LS. Signal, noise, and contrast in nuclear magnetic resonance (NMR) imaging. Journal of computer assisted tomography. 1983;7(3):391-401.

    Article  CAS  PubMed  Google Scholar 

  36. Deoni SC, Rutt BK, Peters TM. Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state. Magn Reson Med. 2003;49(3):515-26.

    Article  PubMed  Google Scholar 

  37. Dietrich O, Raya JG, Reeder SB, Reiser MF, Schoenberg SO. Measurement of signal-to-noise ratios in MR images: influence of multichannel coils, parallel imaging, and reconstruction filters. Journal of magnetic resonance imaging : JMRI. 2007;26(2):375-85.

    Article  PubMed  Google Scholar 

  38. Haradome H, Grazioli L, Al manea K, et al. Gadoxetic acid disodium-enhanced hepatocyte phase MRI: can increasing the flip angle improve focal liver lesion detection? Journal of magnetic resonance imaging : JMRI. 2012;35(1):132-9.

    Article  PubMed  Google Scholar 

  39. Bashir MR, Merkle EM. Improved liver lesion conspicuity by increasing the flip angle during hepatocyte phase MR imaging. Eur Radiol. 2011;21(2):291-4.

    Article  PubMed  Google Scholar 

  40. Motosugi U, Bannas P, Hernando D, Salmani Rahimi M, Holmes JH, Reeder SB. Intraindividual Crossover Comparison of Gadoxetic Acid Dose for Liver MRI in Normal Volunteers. Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine. 2016;15(1):60-72.

    Article  CAS  PubMed  Google Scholar 

  41. EMA. Gadolinium-containing contrast agents2017; vol 2018, no Jan 30, 2018. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Gadolinium-containing_contrast_agents/human_referral_prac_000056.jsp&mid=WC0b01ac05805c516f.

  42. FDA. FDA Drug Safety Communication: FDA warns that gadolinium-based contrast agents (GBCAs) are retained in the body; requires new class warnings2017; vol 2018, no Jan 30, 2018. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Radiology, University of Wisconsin – School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI, 53705, USA

    Gesine Knobloch, Timothy Colgan, Tilman Schubert & Scott B. Reeder

  2. Department of Biomedical Engineering, University of Wisconsin – School of Medicine and Public Health, Madison, WI, USA

    Xiaoke Wang & Scott B. Reeder

  3. Department of Biostatistics and Medical Informatics, University of Wisconsin – School of Medicine and Public Health, Madison, WI, USA

    Kaitlin M. Woo

  4. Clinic for Radiology and Nuclear Medicine, Basel University Hospital, Basel, Switzerland

    Tilman Schubert

  5. Department of Medical Physics, University of Wisconsin – School of Medicine and Public Health, Madison, WI, USA

    Scott B. Reeder

  6. Department of Medicine, University of Wisconsin – School of Medicine and Public Health, Madison, WI, USA

    Scott B. Reeder

  7. Department of Emergency Medicine, University of Wisconsin – School of Medicine and Public Health, Madison, WI, USA

    Scott B. Reeder

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  1. Gesine Knobloch
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  2. Timothy Colgan
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Correspondence to Scott B. Reeder.

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

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Knobloch, G., Colgan, T., Wang, X. et al. Combined gadoxetic acid and gadobenate dimeglumine enhanced liver MRI: a parameter optimization study. Abdom Radiol 45, 220–231 (2020). https://doi.org/10.1007/s00261-019-02265-z

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