Skip to main content
Log in

Brain relaxometry after macrocyclic Gd-based contrast agent

  • Original Article
  • Published:
Clinical Neuroradiology Aims and scope Submit manuscript

Abstract

Purpose

To assess if ratios of T1-weighted (T1w) signal intensity (SI) and quantitative T1 relaxometry (qT1) change on serial administration of macrocyclic gadobutrol.

Methods

A total of 17 glioblastoma patients were scanned at 3.0 T magnetic resonance imaging (MRI) every 6 weeks after tumor resection with standard MRI and T1 and T2 relaxometry before and after gadobutrol administration. On co-registered images T1w SI was measured and relaxation times T1 (qT1) and quantitative T2 (qT2) were quantified in several deep grey matter nuclei as ratios relative to frontal white matter and to the pons. Ratio changes were evaluated over time with a paired t‑test and multiple regression.

Results

An average of 8 (range 5–14) scans per patient were completed. Ratios of T1w SI, qT1 and qT2 remained unchanged for all target regions from the first to the last time point (p > 0.05) and did not correlate with the number of gadobutrol administrations. Multivariate regression showed no significant impact of gadobutrol on qT1 or qT2 ratios, but a significant negative effect on T1w SI ratios. Gender also had no impact on the ratios but age had a significant negative influence on the qT1 ratio.

Conclusion

Multiple administrations of a macrocyclic contrast agent did not change relaxation time T1 ratios in any deep grey matter structure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

GBCA:

Gd-based contrast agent

MRI:

Magnetic resonance imaging

qT1:

T1 relaxation time

qR1:

R1 relaxation rate

qT2:

T2 relaxation time

ROI:

Region of interest

SI:

Signal intensity

T1w:

T1-weighted

TE:

Echo time

TFE:

Ultrafast gradient echo

TI:

Inversion time

TR:

Repetition time

TSE:

Turbo spin echo

References

  1. Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. 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. 2014;270:834–41.

    Article  PubMed  Google Scholar 

  2. Ramalho J, Semelka RC, Ramalho M, Nunes RH, AlObaidy M, Castillo M. Gadolinium-based contrast agent accumulation and toxicity: an update. AJNR Am J Neuroradiol. 2016;37:1192–8.

    Article  CAS  PubMed  Google Scholar 

  3. Bennett CL, Qureshi ZP, Sartor AO, Norris LB, Murday A, Xirasagar S, Thomsen HS. Gadolinium-induced nephrogenic systemic fibrosis: the rise and fall of an iatrogenic disease. Clin Kidney J. 2012;5:82–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Khurram M, Skov L, Rossen K, Thomsen HS, Marckmann P. Nephrogenic systemic fibrosis: a serious iatrogenic disease of renal failure patients. Scand J Urol Nephrol. 2007;41:565–6.

    Article  PubMed  Google Scholar 

  5. Roccatagliata L, Vuolo L, Bonzano L, Pichiecchio A, Mancardi GL. Multiple sclerosis: hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with the secondary progressive subtype. Radiology. 2009;251:503–10.

    Article  PubMed  Google Scholar 

  6. Radbruch A, Weberling LD, Kieslich PJ, Eidel O, Burth S, Kickingereder P, Heiland S, Wick W, Schlemmer H‑P, Bendszus M. Gadolinium retention in the dentate nucleus and Globus Pallidus is dependent on the class of contrast agent. Radiology. 2015;275:150337.

    Article  Google Scholar 

  7. Radbruch A, Weberling LD, Kieslich PJ, Hepp J, Kickingereder P, Wick W, Schlemmer HP, Bendszus M. High-signal intensity in the dentate nucleus and Globus Pallidus on Unenhanced T1-weighted images: evaluation of the Macrocyclic gadolinium-based contrast agent Gadobutrol. Invest Radiol. 2015;50:805–10.

    Article  CAS  PubMed  Google Scholar 

  8. Radbruch A, Haase R, Kickingereder P, Bäumer P, Bickelhaupt S, Paech D, Wick W, Schlemmer HP, Seitz A, Bendszus M. Pediatric brain: no increased signal intensity in the dentate nucleus on unenhanced T1-weighted MR images after consecutive exposure to a Macrocyclic gadolinium-based contrast agent. Radiology. 2017;283:828–36.

    Article  PubMed  Google Scholar 

  9. Radbruch A, Haase R, Kieslich PJ, Weberling LD, Kickingereder P, Wick W, Schlemmer HP, Bendszus M. No signal intensity increase in the dentate nucleus on unenhanced T1-weighted MR images after more than 20 serial injections of Macrocyclic gadolinium-based contrast agents. Radiology. 2017;282:699–707.

    Article  PubMed  Google Scholar 

  10. Chandra T, Mohan S. Role of contrast in MR imaging. Top Magn Reson Imaging. 2016;25:151–156.

    Google Scholar 

  11. Bellin MF, Vasile M, Morel-Precetti S. Currently used non-specific extracellular MR contrast media. Eur Radiol. 2003;13:2688–98.

    Article  CAS  PubMed  Google Scholar 

  12. Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev. 1999;99:2293–352.

    Article  CAS  PubMed  Google Scholar 

  13. Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Ljubisavljevic S. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast age. Eur Radiol. 2016;26:807–15.

    Article  PubMed  Google Scholar 

  14. Tedeschi E, Palma G, Canna A, Cocozza S, Russo C, Borrelli P, Lanzillo R, Angelini V, Postiglione E, Morra VB, Salvatore M, Brunetti A, Quarantelli M. In vivo dentate nucleus MRI relaxometry correlates with previous administration of Gadolinium-based contrast agents. Eur Radiol. 2016;26:4577–84.

    Article  Google Scholar 

  15. Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J, Haruyama T, Kitajima K, Furui S. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology. 2015;276:228–32.

    Article  PubMed  Google Scholar 

  16. Murata N, Gonzalez-Cuyar LF, Murata K, Fligner C, Dills R, Hippe D, Maravilla KR. Macrocyclic and other non-group 1 gadolinium contrast agents deposit low levels of gadolinium in brain and Bone tissue: preliminary results from 9 patients with normal renal function. Invest Radiol. 2016;51:447–53.

    Article  CAS  PubMed  Google Scholar 

  17. McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, Williamson EE, Eckel LJ. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 2015;275:772–82.

    Google Scholar 

  18. Nyúl LG, Udupa JK. On standardizing the MR image intensity scale. Magn Reson Med. 1999;42:1072–81.

    Article  PubMed  Google Scholar 

  19. Deoni SCL. Quantitative relaxometry of the brain. Top Magn Reson Imaging. 2010;21:101–13.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Weiskopf N, Suckling J, Williams G, Correia MMM, Inkster B, Tait R, Ooi C, Bullmore TET, Lutti A. Quantitative multi-parameter mapping of R1, PD*, MT, and R2* at 3T: A multi-center validation. Front Neurosci. 2013;7:1–11.

    Article  Google Scholar 

  21. Müller A, Jurcoane A, Kebir S, Ditter P, Schrader F, Herrlinger U, Tzaridis T, Mädler B, Schild HH, Glas M, Hattingen E. Quantitative T1-mapping detects cloudy-enhancing tumor compartments predicting outcome of patients with glioblastoma. Cancer Med. 2017;6(1):89–99. doi:10.1002/cam4.966.

    Article  PubMed  Google Scholar 

  22. Mädler B, Harris T, MacKay AL. 3D-relaxometry—quantitative T1 and T2 brain mapping at 3T. Proceedings of the 14th scientific meeting, International Society for Magnetic Resonance in Medicine, Seattle, USA, 2006, 14, p. 958.

  23. Fretellier N, Idée JM, Dencausse A, Karroum O, Guerret S, Poveda N, Jestin G, Factor C, Raynal I, Zamia P, Port M, Corot C. Comparative in vivo dissociation of gadolinium chelates in renally impaired rats: a relaxometry study. Invest Radiol. 2011;46:292–300.

    Article  CAS  PubMed  Google Scholar 

  24. Jost G, Frenzel T, Lohrke J, Lenhard DC, Naganawa S, Pietsch H. Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue. Eur Radiol. 2016;27:2877–85.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Frenzel T, Apte C, Jost G, Schöckel L, Lohrke J, Pietsch H. Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents: Comparative Study in Rats. Invest Radiol. 2017;52(7):396–404. doi:10.1097/RLI.0000000000000352.

    Google Scholar 

  26. Badve C, Yu A, Rogers M, Ma D, Liu Y, Schluchter M, Sunshine J, Griswold M, Gulani V. Simultaneous T1 and T2 brain relaxometry in asymptomatic volunteers using magnetic resonance fingerprinting. Tomography. 2015;1:136–44.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gracien RM, Nürnberger L, Hok P, Hof SM, Reitz SC, Rüb U, Steinmetz H, Hilker-Roggendorf R, Klein JC, Deichmann R, Baudrexel S. Evaluation of brain ageing: a quantitative longitudinal MRI study over 7 years. Eur Radiol. 2016;27:1568–76.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank GL for help with statistics, our MRI technicians for excellent technical support and the patients and their families for their participation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elke Hattingen.

Ethics declarations

Conflict of interest

A. Müller, A. Jurcoane, P. Ditter, H. Schild and E Hattingen declare that they have no competing interests. B. Mädler is employee of Philips GmbH.

Additional information

Andreas Müller and Alina Jurcoane contributed equally to the manuscript.

Authors Contribution

Data were analyzed and controlled by authors who were not employed by or a consultant for a company in the medical industry and all authors have seen and approved the revised manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Müller, A., Jurcoane, A., Mädler, B. et al. Brain relaxometry after macrocyclic Gd-based contrast agent. Clin Neuroradiol 27, 459–468 (2017). https://doi.org/10.1007/s00062-017-0608-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00062-017-0608-6

Keywords

Navigation