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01-08-2020 | Magnetic Resonance Imaging | Contrast Media

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

Authors: Katerina Deike-Hofmann, Paula von Lampe, Heinz-Peter Schlemmer, Nikolaos Bechrakis, Christoph Kleinschnitz, Michael Forsting, Alexander Radbruch

Published in: European Radiology | Issue 8/2020

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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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 CrossRefPubMed

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 CrossRefPubMed

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

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRef

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRef

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 CrossRefPubMed

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 CrossRef

21.

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

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 CrossRef

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 CrossRefPubMed

24.

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

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 CrossRef

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

Title: The anterior eye chamber: entry of the natural excretion pathway of gadolinium contrast agents?
Authors: Katerina Deike-Hofmann
Paula von Lampe
Heinz-Peter Schlemmer
Nikolaos Bechrakis
Christoph Kleinschnitz
Michael Forsting
Alexander Radbruch
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Retinoblastoma
Retinoblastoma
Published in: European Radiology / Issue 8/2020
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-020-06762-4

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

Abstract

Objective

Methods

Results

Conclusions

Key Points

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Key Points

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