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Potential Intracranial Gadolinium Deposition in
Children Following Multiple Contrast Enhanced MRI
Examinations: Evaluation of Long Term
Parenchymal Signal Changes
Alex C. Wu, M.D.1
Ihsan Mamoun, M.D.1
Ellen Park, M.D., M.S.1
Unni Udayasankar, M.D.2
1Cleveland
Clinic Children’s, Cleveland, OH
2University of Arizona Medical Center, Tuscan, AZ
DISCLOSURES
The authors have no conflicts of
interest and no financial disclosures.
BACKGROUND
• In adults, a few recent magnetic resonance imaging
(MRI)-autopsy correlation studies have demonstrated
deposition of gadolinium in the brain that correlated with
increase in MRI signals on the T1 sequences at the
globus pallidus and dentate nucleus.1
• Studies suggested gadolinium deposition only with
linear contrast agents compared to macrocyclic agents.2
• No such studies have been reported in the pediatric
population.
1. McDonald RJ, McDonald JS, Kallmes DF, et al. Radiology. 2015; 275(3): 772-82.
2. Radbruch A, Weberling LD, Kieslich PJ, et al. Radiology. 2015; 275(3): 783-91.
PURPOSE
• The purpose of our study is to evaluate if repeated
intravenous administrations of Gadolinium based
contrast agents (GBCA) during MRI studies result in
brain parenchymal signal changes in children.
MATERIALS & METHODS
• Single center, IRB approved retrospective study.
Subjects
41 subjects
(< 18 yo)
Contrast group
(n= 21)
> 4 GBCA MRIs
Control group
(n = 20)
non-Gd MRIs
Exclusion Criteria:
• abnormal liver functions
(AST, Alk-Phos, Total Br)
• abnormal renal functions
(GFR < 60 mL/min)
• metabolic disorders
• congenital malformation
involving the areas of
interests.
• Total of 41 subjects under the age of 18 years and older than 2 years
• Contrast group: 21 subjects, more than 4 GBCA MRI studies between
2008 and 2015.
• Control group: 20 subjects, age/sex matched, multiple non-contrast MRIs.
MATERIALS & METHODS
• Three different contrast agents were used in our institution during the
study period.
gadopentetate
dimeglumine
(Magnevist®)
gadobutrol
(Gadavist®)
gadoterate
meglumine
(Dotraem®)
• Up to 8/10/2012
• 8/11/2012 to
1/11/2015
• 1/12/2015 to
present.
• gadopentetate dimeglumine (Magnevist® | Bayer) ) up to 8/10/2012
• gadobutrol (Gadavist® | Bayer) from 8/11/2012 to 1/11/2015
• gadoterate meglumine (Dotraem® | Guerbet) from 1/12/2015 to present.
• Standard weight-based contrast dose of 0.1 mmol/kg was utilized.
IMAGING ANALYSIS
• All subjects had brain MRI with standardized imaging protocols which
included a pre-contrast coronal T1-weighted sequence.
• Studies were performed on one of the MR scanners within our
healthcare system and included 1.5-T and 3.0-T Siemens scanners
(Siemens, Munich, Germany).
Coronal T1W sequence protocol:
• Flip angle: 90
• Echo time: 17s
• Repetition time: less than 800
• Matrix: 256 x 190
• Field of View: 220-230
• 5mm imaging slice thickness
STATISTICAL ANALYSIS
• On non-contrast coronal T1W images, region of interest (ROI) drawn over
• globus pallidus (GP),
• dentate nucleus (DN),
• thalamus (TH),
• central pons.
• ROIs drawn to include as much of anatomical region as possible.
• Axial T2 sequence used to confirm localization (example below).
Globus
Pallidus
RESULTS
Demographics
Contrast Group
Control Group
Subjects
21
20
Mean Age
7.8 years (0.3–16.6)
8 years (1.6–15.3)
MRIs
11.2 ± 5.4 GBCA MRI
Non-contrast MRI
Study Interval
4.4 years
1.7 years
Main Indication
CNS tumor & follow up
Epilepsy
Contrast Group
• Main study indication was CNS tumor evaluation and follow-up
• 12 WHO I-II glial tumors, 8 had radiation to brain
(2 craniospinal irradiation for medulloblastoma, 6 had focal radiation).
• 6 had concurrent chemotherapy.
•
An average 0.9 (0-2) outside GBCA MR studies with unknown GBCA or
dose prior to receiving care at our institution.
RESULTS
Contrast Dose
Contrast Group
• Although we did not differentiate between different GBCA in our study,
subjects in the contrast group received an average 6.2 doses of
gadopentetate dimeglumine (Magnevist), 4.4 gadobutrol (Gadavist) and 0.7
gadoterate meglumine (Dotraem) during the study interval.
Average Dose
0.7 doses of
gadoterate
meglumine
(Dotraem)
4.4 doses of
gadobutrol
(Gadavist)
6.2 doses of
gadopentetate
dimeglumine
(Magnevist)
RESULTS
MR Signal Analysis
Percent Signal Change
3.0%
2.5%
2.0%
1.5%
p = 0.334
p = 0.585
1.0%
0.5%
0.0%
GP:TH
Contrast Group
DN:Pons
Control Group
The percent increases in T1 signal of both (GP:TH) and (DN:Pons)
between the first to last MRI was higher in the contrast group as compared
to the control group shown above. However, neither was statistically
significant (95% CI: -2.1% to 5.9%, p=0.334) and (95% CI: -3.8% to 6.7%,
p=0.585).
RESULTS
MR Signal Analysis
GP:TH
percent change
Among the contrast group, the percent change in T1 signal (GP:TH) from first to
last MRI tended to decrease as the total number of MRIs increased (slope: -0.4%),
but this was not statistically significant (95% CI: -0.9%0.2%, p=0.211). (Figure 1)
Similarly, there was no statistically significant change of T1 signal (GP:TH) in the
control group (p=0.651).
RESULTS
MR Signal Analysis
DN:Pons
percent change
The percent change in MRI signal (DN:Pons) from first to last MRI tended to
increase as the total number of MRIs increased in the contrast group, but this was
not statistically significant (95% CI: -0.3%~1.5%, p=0.185). (Figure 2)
However, percent change of DN:Pons decreased as the total number of MRIs
increased in the control group (95% CI: -3.1~-0.4%, p=0.012).
DISCUSSION
• Our study differs from recent reports of intracranial
gadolinium deposition in adult subjects
• This may be related to use of more stable Gadolinium
based contrast agent used at our intuition
• It is unclear if children metabolize gadolinium agents at
a different rate compared to adults
DISCUSSION
LIMITATIONS
• Small sample size.
• Many in the contrast group received radiation to the
brain and/or chemotherapy.
• Prior gadolinium based contrast dose prior to receiving
care at our institution.
CONCLUSION
• No significant parenchymal MRI signal change was
observed after multiple GBCA administration in the
pediatric population.
• Our data differs from recent published literature in adult
subject1-3 and suggests no significant intracranial
deposition of GBCA in children.
CONTACT
Unni Udayasankar, M.D.
[email protected]