Impact of Brain Tumors and Radiotherapy on the Presence of Gadolinium in the Brain After Repeated Administration of Gadolinium-based Contrast Agents: an Experimental Study in Rats

Overview

Journal Neuroradiology

Specialties Neurology
Radiology

Date 2019 Jul 13

PMID 31297571

Citations 4

Authors

Gregor Jost

Thomas Frenzel

Janina Boyken

Hubertus Pietsch

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate the impact of blood-brain barrier (BBB) alterations induced by an experimental tumor and radiotherapy on MRI signal intensity (SI) in deep cerebellar nuclei (DCN) and the presence of gadolinium after repeated administration of a linear gadolinium-based contrast agent in rats.

Methods: Eighteen Fischer rats were divided into a tumor (gliosarcoma, GS9L model), a radiotherapy, and a control group. All animals received 5 daily injections (1.8 mmol/kg) of gadopentetate dimeglumine. For tumor-bearing animals, the BBB disruption was confirmed by contrast-enhanced MRI. Animals from the tumor and radiation group underwent radiotherapy in 6 fractions of 5 Gray. The SI ratio between DCN and brain stem was evaluated on T1-weigthed MRI at baseline and 1 week after the last administration. Subsequently, the brain was dissected for gadolinium quantification by inductively coupled plasma-mass spectrometry. Statistical analysis was done with the Kruskal-Wallis test.

Results: An increased but similar DCN/brain stem SI ratio was found for all three groups (p = 0.14). The gadolinium tissue concentrations (median, nmol/g) were 6.7 (tumor), 6.3 (radiotherapy), and 6.8 (control) in the cerebellum (p = 0.64) and 17.8/14.6 (tumor), 20.0/18.9 (radiotherapy), and 17.8/15.9 (control) for the primary tumor (p = 0.98) and the contralateral hemisphere (p = 0.41) of the cerebrum, respectively.

Conclusion: An experimental brain tumor treated by radiotherapy or radiotherapy alone did not alter DCN signal hyperintensity and gadolinium concentration in the rat brain 1 week after repeated administration of gadopentetate. This suggests that a local BBB disruption does not affect the amount of retained gadolinium in the brain.

Citing Articles

Ten years of gadolinium retention and deposition: ESMRMB-GREC looks backward and forward.

van der Molen A, Quattrocchi C, Mallio C, Dekkers I Eur Radiol. 2023; 34(1):600-611.

PMID: 37804341 PMC: 10791848. DOI: 10.1007/s00330-023-10281-3.

Blood-brain barrier permeability following conventional photon radiotherapy - A systematic review and meta-analysis of clinical and preclinical studies.

Hart E, Ode Z, Derieppe M, Groenink L, Heymans M, Otten R Clin Transl Radiat Oncol. 2022; 35:44-55.

PMID: 35601799 PMC: 9117815. DOI: 10.1016/j.ctro.2022.04.013.

Stability of MRI contrast agents in high-energy radiation of a 1.5T MR-Linac.

Wang J, Salzillo T, Jiang Y, Mackeyev Y, Fuller C, Chung C Radiother Oncol. 2021; 161:55-64.

PMID: 34089753 PMC: 8324543. DOI: 10.1016/j.radonc.2021.05.023.

Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats.

Habermeyer J, Boyken J, Harrer J, Canneva F, Ratz V, Moceri S Sci Rep. 2020; 10(1):22385.

PMID: 33372182 PMC: 7769977. DOI: 10.1038/s41598-020-79374-z.

References

Robert P, Violas X, Grand S, Lehericy S, Idee J, Ballet S . Linear Gadolinium-Based Contrast Agents Are Associated With Brain Gadolinium Retention in Healthy Rats. Invest Radiol. 2015; 51(2):73-82. PMC: 4747982. DOI: 10.1097/RLI.0000000000000241. View

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(3):834-41. DOI: 10.1148/radiol.13131669. View

Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idee J . T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats: Difference Between Linear and Macrocyclic Agents. Invest Radiol. 2015; 50(8):473-80. PMC: 4494686. DOI: 10.1097/RLI.0000000000000181. View

Arena F, Bardini P, Blasi F, Gianolio E, Marini G, La Cava F . Gadolinium presence, MRI hyperintensities, and glucose uptake in the hypoperfused rat brain after repeated administrations of gadodiamide. Neuroradiology. 2018; 61(2):163-173. DOI: 10.1007/s00234-018-2120-3. View

Gianolio E, Bardini P, Arena F, Stefania R, Di Gregorio E, Iani R . Gadolinium Retention in the Rat Brain: Assessment of the Amounts of Insoluble Gadolinium-containing Species and Intact Gadolinium Complexes after Repeated Administration of Gadolinium-based Contrast Agents. Radiology. 2017; 285(3):839-849. DOI: 10.1148/radiol.2017162857. View

Iliff J, Wang M, Liao Y, Plogg B, Peng W, Gundersen G . A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012; 4(147):147ra111. PMC: 3551275. DOI: 10.1126/scitranslmed.3003748. View

Greene-Schloesser D, Robbins M, Peiffer A, Shaw E, Wheeler K, Chan M . Radiation-induced brain injury: A review. Front Oncol. 2012; 2:73. PMC: 3400082. DOI: 10.3389/fonc.2012.00073. View

Adin M, Kleinberg L, Vaidya D, Zan E, Mirbagheri S, Yousem D . Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration. AJNR Am J Neuroradiol. 2015; 36(10):1859-65. PMC: 4878403. DOI: 10.3174/ajnr.A4378. View

Berger F, Kubik-Huch R, Niemann T, Schmid H, Poetzsch M, Froehlich J . Gadolinium Distribution in Cerebrospinal Fluid after Administration of a Gadolinium-based MR Contrast Agent in Humans. Radiology. 2018; 288(3):703-709. DOI: 10.1148/radiol.2018171829. View

10.

Radbruch A, Haase R, Kieslich P, Weberling L, Kickingereder P, Wick W . 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. 2016; 282(3):699-707. DOI: 10.1148/radiol.2016162241. View

11.

Weinmann H, Brasch R, Press W, Wesbey G . Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. AJR Am J Roentgenol. 1984; 142(3):619-24. DOI: 10.2214/ajr.142.3.619. View

12.

Boyken J, Frenzel T, Lohrke J, Jost G, Pietsch H . Gadolinium Accumulation in the Deep Cerebellar Nuclei and Globus Pallidus After Exposure to Linear but Not Macrocyclic Gadolinium-Based Contrast Agents in a Retrospective Pig Study With High Similarity to Clinical Conditions. Invest Radiol. 2018; 53(5):278-285. PMC: 5902136. DOI: 10.1097/RLI.0000000000000440. View

13.

Tamrazi B, Liu C, Cen S, Nelson M, Dhall G, Nelson M . Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity. Radiology. 2018; 289(1):188-194. DOI: 10.1148/radiol.2018173057. View

14.

Ueno M, Chiba Y, Murakami R, Matsumoto K, Kawauchi M, Fujihara R . Blood-brain barrier and blood-cerebrospinal fluid barrier in normal and pathological conditions. Brain Tumor Pathol. 2016; 33(2):89-96. DOI: 10.1007/s10014-016-0255-7. View

15.

Henderson S, Kimler B, Morantz R . Radiation therapy of 9L rat brain tumors. Int J Radiat Oncol Biol Phys. 1981; 7(4):497-502. DOI: 10.1016/0360-3016(81)90136-x. View

16.

Jost G, Frenzel T, Lohrke J, Lenhard D, 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(7):2877-2885. PMC: 5486780. DOI: 10.1007/s00330-016-4654-2. View

17.

Frenzel T, Lengsfeld P, Schirmer H, Hutter J, Weinmann H . Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 degrees C. Invest Radiol. 2008; 43(12):817-28. DOI: 10.1097/RLI.0b013e3181852171. View

18.

Robert P, Fingerhut S, Factor C, Vives V, Letien J, Sperling M . One-year Retention of Gadolinium in the Brain: Comparison of Gadodiamide and Gadoterate Meglumine in a Rodent Model. Radiology. 2018; 288(2):424-433. DOI: 10.1148/radiol.2018172746. View

19.

Radbruch A, Weberling L, Kieslich P, Eidel O, Burth S, Kickingereder P . Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology. 2015; 275(3):783-91. DOI: 10.1148/radiol.2015150337. View

20.

Verheggen I, van Boxtel M, Verhey F, Jansen J, Backes W . Interaction between blood-brain barrier and glymphatic system in solute clearance. Neurosci Biobehav Rev. 2018; 90:26-33. DOI: 10.1016/j.neubiorev.2018.03.028. View