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The anterior eye chamber: entry of the natural excretion pathway of gadolinium contrast agents?

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Abstract

Objective

Previous studies provided evidence that gadolinium can be found in the aqueous chamber (AC) of the eye several hours post injection (p.i.) of gadolinium-based contrast agents (GBCAs). This study aimed to investigate whether gadolinium can be detected promptly after injection of a macrocyclic GBCA on contrast-enhanced T1-weighted MRI in the AC of children.

Methods

This retrospective study encompassed MRI of 200 healthy eyes of children suffering from retinoblastoma of the contralateral eye. MRI was performed with an orbital coil with the children in a state of general anesthesia. Differences of signal intensity ratios (∆SIRs) of the AC to the lens were determined between pre and post contrast-enhanced T1-weighted images (Dotarem®, Guerbet, 0.1 ml/kg body weight, mean (standard deviation) p.i. time = 12:24 (± 2:31) min).

Results

A highly significant signal intensity increase was found in the AC of healthy eyes 12 min after GBCA injection (median ∆SIR (interquartile range) = + 0.08 (0.05–0.12), p < 0.0001). In addition, gadolinium enhancement showed a strong negative correlation with children’s age in multivariate analysis with adjustment for p.i. time (p < 0.0001).

Conclusions

GBCA leakage into the AC of healthy infantile eyes was found promptly after injection. The negative correlation between patient age and GBCA enhancement might be explained by a maturation process of the blood-aqueous barrier or Schlemm’s canal. Future studies should assess the duration and potential diagnostic applications as well as possible safety concerns of gadolinium presence in the AC.

Key Points

• Leakage of gadolinium-based contrast agent into the aqueous chamber of infantile eyes was found promptly after intravenous injection (p < 0.0001).

• Gadolinium enhancement of the anterior eye chamber was negatively correlated with the children’s age (p < 0.0001).

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Abbreviations

∆SIR:

Difference of anterior chamber-to-lens signal intensity ratio

AC:

Aqueous chamber / anterior chamber

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

FoV:

Field of view

GBCA:

Gadolinium-based contrast agent

GS:

Glymphatic system

IQR:

Interquartile range

MRI:

Magnetic resonance imaging

p.i.:

Post injection

ROI:

Region of interest

SD:

Standard deviation

SI:

Signal intensity

SIR:

Anter chamber-to-lens signal intensity ratio

References

  1. Taoka T, Jost G, Frenzel T, Naganawa S, Pietsch H (2018) Impact of the glymphatic system on the kinetic and distribution of gadodiamide in the rat brain. Invest Radiol 53(9):529–534. https://doi.org/10.1097/RLI.0000000000000473

    Article  CAS  PubMed  Google Scholar 

  2. Jost G, Frenzel T, Lohrke J, Lenhard DC, Naganawa S, Pietsch H (2017) 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 27(7):2877–2885. https://doi.org/10.1007/s00330-016-4654-2

    Article  PubMed  Google Scholar 

  3. Lohrke J, Frisk A, Frenzel T et al (2017) Histology and gadolinium distribution in the rodent brain after the administration of cumulative high doses of linear and macrocyclic gadolinium-based contrast agents. Invest Radiol 52(6):324–333. https://doi.org/10.1097/RLI.0000000000000344

  4. Deike-Hofmann K, Reuter J, Haase R et al (2019) Glymphatic pathway of gadolinium-based contrast agents through the brain: overlooked and misinterpreted. Invest Radiol 54(4):229–237. https://doi.org/10.1097/RLI.0000000000000533

    Article  CAS  PubMed  Google Scholar 

  5. Hitomi E, Simpkins AN, Luby M, Latour LL, Leigh RJ, Leigh R (2018) Blood–ocular barrier disruption in acute stroke patients. Neurology. 90(11):e915–e923. https://doi.org/10.1212/WNL.0000000000005123

    Article  PubMed  PubMed Central  Google Scholar 

  6. Harrington D, D’Agostino RB, Gatsonis C et al (2019) New guidelines for statistical reporting in the journal. N Engl J Med 381(3):285–286. https://doi.org/10.1056/nejme1906559

    Article  PubMed  Google Scholar 

  7. Taoka T, Naganawa S (2018) Gadolinium-based contrast media, cerebrospinal fluid and the glymphatic system: possible mechanisms for the deposition of gadolinium in the brain. Magn Reson Med Sci 17(2):111–119. https://doi.org/10.2463/mrms.rev.2017-0116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Naganawa S, Nakane T, Kawai H, Taoka T (2017) Gd-based contrast enhancement of the perivascular spaces in the basal ganglia. Magn Reson Med Sci 16:61–65. https://doi.org/10.2463/mrms.mp.2016-0039

    Article  CAS  PubMed  Google Scholar 

  9. Iliff JJ, Lee H, Yu M et al (2013) Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest 123(3):1299–1209. https://doi.org/10.1172/JCI67677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kress BT, Iliff JJ, Xia M et al (2014) Impairment of paravascular clearance pathways in the aging brain. Ann Neurol 76(6):845–861. https://doi.org/10.1002/ana.24271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ringstad G, Valnes LM, Dale AM et al (2018) Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI Insights 3(13):1–17. https://doi.org/10.1172/jci.insight.121537

  12. Ringstad G, Vatnehol SAS, Eide PK (2017) Glymphatic MRI in idiopathic normal pressure hydrocephalus. Brain. 140(10):2691–2705. https://doi.org/10.1093/brain/awx191

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2013) 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):834–841. https://doi.org/10.1148/radiol.13131669

    Article  PubMed  Google Scholar 

  14. Iliff JJ, Wang M, Liao Y et al (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid b. Sci Transl Med 4(147):ra111. https://doi.org/10.1126/scitranslmed.3003748

    Article  CAS  Google Scholar 

  15. Bill A (1968) Capillary permeability to and extravascular dynamics of myoglobin, albumin and gammaglobulin in the uvea. Acta Physiol Scand 73(1–2):204–219. https://doi.org/10.1111/j.1748-1716.1968.tb04097.x

    Article  CAS  PubMed  Google Scholar 

  16. Raviola G (1977) The structural basis of the blood-ocular barriers. Exp Eye Res 25(1):27–63. https://doi.org/10.1016/S0014-4835(77)80009-2

    Article  PubMed  Google Scholar 

  17. Kinsey VE, Williamson MB (1949) Investigation of the blood-aqueous barrier in the newborn. II To inulin. Am J Ophthalmol 32(4):509–512. https://doi.org/10.1016/0002-9394(49)90875-2

    Article  CAS  PubMed  Google Scholar 

  18. Kinsey E, Blanche J, Terry TL (1945) Development of secretory function of ciliary body in the rabbit eye evaluated from ascorbic acid concentrations and changes in volume. J Gen Physiol 34(5):415–417. https://doi.org/10.1001/archopht.1945.00890190419013

    Article  CAS  Google Scholar 

  19. Kinsey VE, Jackson B (1949) Investigation of the blood-aqueous barrier in the newborn. I. To ascorbic acid. Am J Ophthalmol 32(3):374–378. https://doi.org/10.1016/0002-9394(49)91930-3

    Article  CAS  PubMed  Google Scholar 

  20. Bembridge BA, Pirie A (2015) Biochemical and histological changes in developing rabbit eyes. Br J Ophthalmol 35(12):784–789. https://doi.org/10.1136/bjo.35.12.784

    Article  Google Scholar 

  21. Kupfer C, Ross K (1971) The development of outflow facility in human eyes. Invest Ophthalmol 10(7):513–517 https://iovs.arvojournals.org/

    CAS  PubMed  Google Scholar 

  22. Pandolfi M, Åstedt B (1971) Outflow resistance in the foetal eye. Acta Ophthalmol (Copenh) 49(2):344–350. https://doi.org/10.1111/j.1755-3768.1971.tb00959.x

    Article  CAS  Google Scholar 

  23. Oshika T, Kato S, Funatsu H (1989) Quantitative assessment of aqueous flare intensity in diabetes. Graefes Arch Clin Exp Ophthalmol 227(6):518–520. https://doi.org/10.1007/BF02169443

    Article  CAS  PubMed  Google Scholar 

  24. Kubota T, Küchle M, Nguyen NX (1994) Aqueous flare in eyes with age-related macular degeneration. Jpn J Ophthalmol 38(1):67–70

    CAS  PubMed  Google Scholar 

  25. Chen M-S, Hou P-K, Tai T-Y, Lin BJ (2008) Blood-ocular barriers. Tzu Chi Med J 20(1):25–34. https://doi.org/10.1016/S1016-3190(08)60004-X

    Article  Google Scholar 

  26. Sawa M (2017) Laser flare-cell photometer: principle and significance in clinical and basic ophthalmology. Jpn J Ophthalmol 61(1):21–42. https://doi.org/10.1007/s10384-016-0488-3

    Article  CAS  PubMed  Google Scholar 

  27. Radbruch A, Roberts DR, Clement O, Rovira A, Quattrocchi CC (2017) Chelated or dechelated gadolinium deposition. Lancet Neurol 16(12):955. https://doi.org/10.1016/S1474-4422(17)30365-4

    Article  PubMed  Google Scholar 

  28. Radbruch A, Richter H, Fingerhut S et al (2019) Gadolinium deposition in the brain in a large animal model. Invest Radiol 54(9):531–536. https://doi.org/10.1097/RLI.0000000000000575

    Article  CAS  PubMed  Google Scholar 

  29. Robert P, Fingerhut S, Factor C et al (2018) One-year retention of gadolinium in the brain: comparison of gadodiamide and gadoterate meglumine in a rodent model. Radiology. 288(2):424–433. https://doi.org/10.1148/radiol.2018172746

    Article  PubMed  Google Scholar 

  30. Jost G, Frenzel T, Boyken J, Lohrke J, Nischwitz V, Pietsch H (2018) Long-term excretion of gadolinium-based contrast agents: linear versus macrocyclic agents in an experimental rat model. Radiology. 290(2):340–348. https://doi.org/10.1148/radiol.2018180135

    Article  PubMed  Google Scholar 

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Acknowledgments

We wish to acknowledge the help provided by PD Dr. Holland-Letz, Department of Biostatistics, German Cancer Research Center.

Funding

The authors state that this work has not received any funding.

Author information

Authors and Affiliations

  1. Department of Radiology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 223, 69120, Heidelberg, Germany

    Katerina Deike-Hofmann & Heinz-Peter Schlemmer

  2. Department of Radiology, University Clinic Essen, Essen, Germany

    Paula von Lampe, Michael Forsting & Alexander Radbruch

  3. Department of Ophthalmology, University Clinic Essen, Essen, Germany

    Nikolaos Bechrakis

  4. Department of Neurology, University Clinic Essen, Essen, Germany

    Christoph Kleinschnitz

Authors
  1. Katerina Deike-Hofmann
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  2. Paula von Lampe
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  3. Heinz-Peter Schlemmer
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  4. Nikolaos Bechrakis
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  5. Christoph Kleinschnitz
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  6. Michael Forsting
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  7. Alexander Radbruch
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Corresponding author

Correspondence to Katerina Deike-Hofmann.

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Guarantor

The scientific guarantor of this publication is Prof. Alexander Radbruch.

Conflict of interest

The authors of this manuscript declare relationships with the following companies:

Alexander Radbruch: Guerbet, Bayer, GE.

Katerina Deike-Hofmann: Guerbet, Bayer, GE.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the Institutional Review Board.

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Institutional Review Board approval was obtained.

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• Retrospective

• Observational

• Performed at one institution

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Electronic supplementary material

ESM 1

Figure e-1, Comparison of differences in signal intensity ratios (∆SIRs) with and without activation of prescan normalization filter (PDF 4.65 kb)

ESM 2

Figure e-2, Residuals of the linear (A) and exponential (B) fitting model (PDF 68.9 kb)

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Deike-Hofmann, K., von Lampe, P., Schlemmer, HP. et al. The anterior eye chamber: entry of the natural excretion pathway of gadolinium contrast agents?. Eur Radiol 30, 4633–4640 (2020). https://doi.org/10.1007/s00330-020-06762-4

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  • DOI: https://doi.org/10.1007/s00330-020-06762-4

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