Comprehensive evaluation of macroscopic and microscopic myocardial fibrosis by cardiac MR: intra-individual comparison of gadobutrol versus gadoterate meglumine

  • Amir Ali Rahsepar
  • Ahmadreza Ghasemiesfe
  • Kenichiro Suwa
  • Ryan S. Dolan
  • Monda L. Shehata
  • Monica J. Korell
  • Nivedita K. Naresh
  • Michael Markl
  • Jeremy D. Collins
  • James C. Carr



Late gadolinium enhancement cardiac MR (LGE-CMR) and extracellular volume fraction (ECV-CMR) are widely used to evaluate macroscopic and microscopic myocardial fibrosis. Macrocyclic contrast media are increasingly used off-label for myocardial scar assessment, given the superior safety profile of these agents. We aimed to assess the performance of two macrocyclic contrast agents, gadoterate meglumine and gadobutrol, for the evaluation of myocardial scar.

Material and methods

Forty subjects (61 ± 11 years, 67.5% men) who underwent LGE-CMR using gadobutrol were prospectively recruited for a research CMR scan using same-dose gadoterate meglumine (0.2 mmol/kg) at 1.5 T. Myocardial scar quantification was performed using a short-axis phase-sensitive inversion recovery (PSIR) Turbo-FLASH and steady-state free precession (SSFP) images. Pre- and post-contrast T1-mapping was employed to assess myocardial ECV. An intraclass correlation coefficient (ICC) was used to check for reliability between the two contrast agents.


Using manual thresholding on PSIR Turbo-FLASH images, mean LGE scar percentage (LGE%) was 9.9 ± 9.7% and 9.4 ± 9.7% for gadobutrol and gadoterate meglumine, respectively (p > 0.05) (ICC: 0.99, 95% CI: 0.97–0.99). Using the PSIR SSFP technique and manual thresholding, LGE% averaged 7.5 ± 9.0% and 7.1 ± 8.6% for gadobutrol and gadoterate meglumine, respectively (p > 0.05) (ICC: 0.99, 95% CI: 0.98–0.99). Average ECV with gadobutrol and gadoterate meglumine were similar at 28.40 ± 4.88 and 28.46 ± 4.73 (p > 0.05) with a strong correlation (ICC: 0.98, 95% CI: 0.94–0.99).


We found LGE- and ECV-CMR values derived from gadoterate meglumine comparable to values derived from gadobutrol. Gadoterate meglumine has a comparable performance to gadobutrol in identifying LGE-derived myocardial scar both qualitatively and quantitatively.

Key Points

• Late gadolinium-enhancement cardiac MR (LGE-MR) and extracellular volume (ECV) fraction are widely used to evaluate macroscopic and microscopic myocardial fibrosis.

• Macrocyclic contrast media are increasingly used off-label for myocardial scar assessment, given the presumed superior safety profile of these agents.

• LGE- and ECV-CMR values derived from gadoterate meglumine are comparable to values derived from gadobutrol.


Heart Magnetic resonance imaging Contrast agents Scar 



Confidence interval


Cardiac magnetic resonance


Contrast-to-noise ratio


Extracellular volume


Gadolinium-based contrast agents


Glomerular filtration rate


Intraclass correlation coefficients


Late gadolinium enhancement


Left ventricle


Modified Look-Locker inversion recovery


Phase-sensitive inversion recovery


Signal intensity


Signal-to-noise ratio


Steady-state free precession



We would like to particularly thank all the patients who participated in our study.


This study has received funding by Geurbet, LLC.

Compliance with ethical standards


The scientific guarantor of this publication is Professor James C. Carr, MD.

Conflict of interest

Dr. James Carr and Dr. Jeremy Collins are members of the advisory board of Guerbet, LLC.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional review board approval was obtained.


• Prospective

• Diagnostic study

• Performed at one institution


  1. 1.
    Kino A, Zuehlsdorff S, Sheehan JJ et al (2009) Three-dimensional phase-sensitive inversion-recovery turbo FLASH sequence for the evaluation of left ventricular myocardial scar. AJR Am J Roentgenol 193(5):W381–W388CrossRefGoogle Scholar
  2. 2.
    Kim RJ, Fieno DS, Parrish TB et al (1999) Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 100(19):1992–2002CrossRefGoogle Scholar
  3. 3.
    Schelbert EB, Hsu LY, Anderson SA et al (2010) Late gadolinium-enhancement cardiac magnetic resonance identifies postinfarction myocardial fibrosis and the border zone at the near cellular level in ex vivo rat heart. Circ Cardiovasc Imaging 3(6):743–752CrossRefGoogle Scholar
  4. 4.
    Gulati A, Jabbour A, Ismail TF et al (2013) Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 309(9):896–908CrossRefGoogle Scholar
  5. 5.
    Kim RJ, Wu E, Rafael A et al (2000) The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 343(20):1445–1453CrossRefGoogle Scholar
  6. 6.
    Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA (2011) Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 57(8):891–903CrossRefGoogle Scholar
  7. 7.
    Ambale-Venkatesh B, Lima JA (2015) Cardiac MRI: a central prognostic tool in myocardial fibrosis. Nat Rev Cardiol 12(1):18–29CrossRefGoogle Scholar
  8. 8.
    Kellman P, Wilson JR, Xue H, Ugander M, Arai AE (2012) Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method. J Cardiovasc Magn Reson 14:63CrossRefGoogle Scholar
  9. 9.
    Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S (2016) Cardiac T1 Mapping and Extracellular Volume (ECV) in clinical practice: a comprehensive review. J Cardiovasc Magn Reson 18(1):89Google Scholar
  10. 10.
    Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC (2014) Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation. Invest Radiol 49(10):685–690Google Scholar
  11. 11.
    Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 270(3):834–841CrossRefGoogle Scholar
  12. 12.
    Kanda T, Osawa M, Oba H et al (2015) High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology 275(3):803–809CrossRefGoogle Scholar
  13. 13.
    Idée JM, Port M, Robic C, Medina C, Sabatou M, Corot C (2009) Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging 30(6):1249–1258Google Scholar
  14. 14.
    Kim RJ, Shah DJ, Judd RM (2003) How we perform delayed enhancement imaging. J Cardiovasc Magn Reson 5(3):505–514CrossRefGoogle Scholar
  15. 15.
    Messroghli DR, Greiser A, Fröhlich M, Dietz R, Schulz-Menger J (2007) Optimization and validation of a fully-integrated pulse sequence for modified look-locker inversion-recovery (MOLLI) T1 mapping of the heart. J Magn Reson Imaging 26(4):1081–1086CrossRefGoogle Scholar
  16. 16.
    Stirrat J, Joncas SX, Salerno M, Drangova M, White J (2015) Influence of phase correction of late gadolinium enhancement images on scar signal quantification in patients with ischemic and non-ischemic cardiomyopathy. J Cardiovasc Magn Reson 17:66CrossRefGoogle Scholar
  17. 17.
    Vermes E, Childs H, Carbone I, Barckow P, Friedrich MG (2013) Auto-threshold quantification of late gadolinium enhancement in patients with acute heart disease. J Magn Reson Imaging 37(2):382–390CrossRefGoogle Scholar
  18. 18.
    Mikami Y, Kolman L, Joncas SX et al (2014) Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 16:85CrossRefGoogle Scholar
  19. 19.
    Dietrich O, Raya JG, Reeder SB, Reiser MF, Schoenberg SO (2007) Measurement of signal-to-noise ratios in MR images: influence of multichannel coils, parallel imaging, and reconstruction filters. J Magn Reson Imaging 26(2):375–385CrossRefGoogle Scholar
  20. 20.
    Cerqueira MD, Weissman NJ, Dilsizian V et al (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105(4):539–542CrossRefGoogle Scholar
  21. 21.
    Moon JC, Messroghli DR, Kellman P et al (2013) Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of cardiology consensus statement. J Cardiovasc Magn Reson 15:92CrossRefGoogle Scholar
  22. 22.
    Assomull RG, Prasad SK, Lyne J et al (2006) Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy. J Am Coll Cardiol 48(10):1977–1985CrossRefGoogle Scholar
  23. 23.
    Bello D, Fieno DS, Kim RJ et al (2005) Infarct morphology identifies patients with substrate for sustained ventricular tachycardia. J Am Coll Cardiol 45(7):1104–1108CrossRefGoogle Scholar
  24. 24.
    Wagner A, Mahrholdt H, Holly TA et al (2003) Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet 361(9355):374–379CrossRefGoogle Scholar
  25. 25.
    Wagner M, Schilling R, Doeblin P et al (2013) Macrocyclic contrast agents for magnetic resonance imaging of chronic myocardial infarction: intraindividual comparison of gadobutrol and gadoterate meglumine. Eur Radiol 23(1):108–114CrossRefGoogle Scholar
  26. 26.
    Huber A, Schoenberg SO, Spannagl B et al (2006) Single-shot inversion recovery TrueFISP for assessment of myocardial infarction. AJR Am J Roentgenol 186(3):627–633CrossRefGoogle Scholar
  27. 27.
    Gai N, Turkbey EB, Nazarian S et al (2011) T1 mapping of the gadolinium-enhanced myocardium: adjustment for factors affecting interpatient comparison. Magn Reson Med 65(5):1407–1415CrossRefGoogle Scholar
  28. 28.
    Kawel N, Nacif M, Zavodni A et al (2012) T1 mapping of the myocardium: intra-individual assessment of post-contrast T1 time evolution and extracellular volume fraction at 3T for Gd-DTPA and Gd-BOPTA. J Cardiovasc Magn Reson 14:26CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  • Amir Ali Rahsepar
    • 1
    • 2
  • Ahmadreza Ghasemiesfe
    • 1
    • 2
  • Kenichiro Suwa
    • 1
  • Ryan S. Dolan
    • 1
  • Monda L. Shehata
    • 1
  • Monica J. Korell
    • 1
  • Nivedita K. Naresh
    • 1
  • Michael Markl
    • 1
  • Jeremy D. Collins
    • 1
    • 3
  • James C. Carr
    • 1
  1. 1.Department of Radiology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Department of Radiology, Yale New Haven HealthBridgeport HospitalBridgeportUSA
  3. 3.Department of RadiologyMayo ClinicRochesterUSA

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