The switch from the linear gadolinium-based contrast agent (GBCA) gadopentate dimeglumine (Gd_DTPA) to the macrocyclic GBCA gadobutrol is associated with a decrease of the T1 signal intensity (SI) in brain gray matter nuclei. The effects of the switch to other macrocyclic GBCAs are not yet established.
Purpose
To explore the effects of switching from Gd-DTPA to the macrocyclic GBCA gadoterate meglumine (Gd-DOTA) in pediatric patients.
Material and Methods
We measured the pallidus/middle cerebellar peduncle (MCP) SI ratio and the dentate/MCP SI ratio in pre-contrast sagittal T1-weighted spin-echo images in nine patients who had received ≥6 administrations of Gd-DTPA and then of Gd-DOTA, in 18 patients who had received ≥6 administrations of Gd-DOTA alone, and in nine age-matched controls without prior GBCA administrations. Serial assessment was performed in patients who switched from Gd-DTPA to Gd-DOTA. Finally, the rate of change of pallidal/MCP and dentate/MCP SI ratios between the first and last Gd-DOTA administrations was compared.
Results
The pallidal/MCP and dentate/MCP SI ratios were (P < 0.05) higher in patients with prior Gd-DTPA and Gd-DOTA administrations compared to the controls. After the switch, the pallidal/MCP SI ratio increased in nine patients and the dentate/MCP ratio in seven patients. The rate of change of pallidal/MCP SI ratio after Gd-DOTA was higher (P < 0.01) in patients who had previously received Gd-DTPA (mean 2.89 ± 2.6%) than in patients who had received Gd-DOTA alone (mean 0.53 ± 0.89%).
Conclusion
T1 SI in gray matter nuclei does not decrease after switching from Gd-DTPA to Gd-DOTA. The switch effects from Gd-DTPA to each macrocyclic GBCA should be individually evaluated.
KandaTIshiiKKawaguchiH, et al.
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. Radiology2014;
270:834–841.
2.
ZhangYCaoYShihGL, et al.
Extent of signal hyperintensity on unenhanced T1-weighted brain MR images after more than 35 administrations of linear Gadolinium-based contrast agents. Radiology2017;
282:516–525.
3.
RamalhoXJSemelkaRCRamalhoM, et al.
Gadolinium-based contrast agent accumulation and toxicity: an update. AJNR Am J Neuroradiol2016;
37:1192–1198.
4.
RadbruchA.Are some agents less likely to deposit gadolinium in the brain?Magn Reson Imaging2016;
34:1351–1354.
5.
GulaniVCalamanteFShellockFG, et al.
Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol2017;
16:564–570.
6.
QuattrocchiCCRamalhoJvan der MolenAJ, et al.
Standardized assessment of the signal intensity increase on unenhanced T1-weighted images in the brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force position statement. Eur Radiol2018;
29:3959–3967.
7.
McDonaldRJLevineDWeinrebJ, et al.
Gadolinium retention: a research roadmap from the 2018 NIH/ACR/RSNA workshop on gadolinium chelates. Radiology2018;
289:517–534.
8.
McDonaldRJMcDonaldJSKallmesDF, et al.
Intracranial gadolinium deposition after contrast enhanced MR imaging. Radiology2015;
275:772–782.
9.
KandaTFukusatoTMatsudaM, et al.
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. Radiology2015;
276:228–232.
10.
McDonaldRJMcDonaldJSKallmesDF, et al.
Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology2017;
285:546–554.
11.
RobertPFingerhutSFactorC, et al.
One-year retention of gadolinium in the brain: comparison of gadodiamide and gadoterate meglumine in a rodent model. Radiology2018;
288:424–433.
12.
RadbruchA.Gadolinium deposition in the brain: we need to differentiate between chelated and dechelated gadolinium. Radiology2018;
288:434–435.
13.
RobertsDRChatterjeeAR.The critical need for pediatric and juvenile animal research addressing gadolinium retention in the developing body.Invest Radiol2019;
54:72–75.
14.
RobertPLehericySGrandS, et al.
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 Radiol2015;
50:473–480.
15.
JostGLenhardDCSieberMA, et al.
Signal increase on unenhanced T1-weighted images in the rat brain after repeated, extended doses of gadolinium-based contrast agents: comparison of linear and macrocyclic agents. Invest Radiol2016;
51:83–89.
16.
LohrkeJFriskALFrenzelT, et al.
Histology and gadolinium distribution in the rodent brain after the administration of cumulative high doses of linear and macrocyclic gadolinium-based contrast agents. Invest Radiol2017;
52:324–333.
17.
FrenzelTApteCJostG, et al.
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 Radiol2017;
52:396–404.
18.
BoykenJFrenzelTLohrkeJ, et al.
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 Radiol2018;
53:278–285.
19.
BussiSCoppoABotteronC, et al.
Differences in gadolinium retention after repeated injections of macrocyclic MR contrast agents to rats. J Magn Reson Imaging2018;
47:746–752.
RadbruchAWeberlingLDKieslichPJ, et al.
lntraindividual analysis of signal intensity changes in the dentate nucleus after consecutive serial applications of linear and macrocyclic gadolinium-based contrast agents. Invest Radiol2016;
51:683–690.
22.
BehzadiAHFarooqZZhaoY, et al.
Dentate nucleus signal intensity decrease on T1-weighted MR images after switching from gadopentate dimeglumine to gadobutrol. Radiology2018;
287:816–823.
23.
RoweSKRodriguezDCohenE, et al.
Switching from linear to macrocyclic gadolinium-based contrast agents halts the relative T1-weighted signal increase in deep gray matter of children with brain tumors: a retrospective study. J Magn Reson Imaging2020;
51:288–295.
24.
Rossi EspagnetMCBernardiBPasquiniL, et al.
Signal intensity at unenhanced T1 weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children. Pediatr Radiol2017;
47:1345–1352.
25.
SplendianiAPerriMMarsecanoC, et al.
Effects of serial macrocyclic-based contrast materials gadoterate meglumine and gadobutrol administrations on gadolinium-related dentate nuclei signal increases in unenhanced T1-weighted brain: a retrospective study in 158 multiple sclerosis (MS) patients. Radiol Med2018;
123:125–134.
26.
TopcuogluEDTopcuogluOMSemizOysuA, et al.
Does gadoterate meglumine cause Gadolinium retention in the brain of children? A case–control study. J Magn Reson Imaging2020;
51:1471–1477.
27.
Tortori-DonatiPRossiA.Pediatric Neuroradiology, Brain. Head, Neck and Spine.
Berlin:
Springer, 2005.
28.
AdinMEKleinbergLVaidyaD, et al.
Hyperintense dentate nuclei on T1-weighted MRI: Relation to repeat gadolinium administration. AJNR Am J Neuroradiol2016;
36:1859–1865.
29.
TamraziBNguyenBLiuCJ, et al.
Changes in signal intensity of the dentate nucleus and globus pallidus in pediatric patients: impact of brain irradiation and presence of primary brain tumors independent of linear gadolinium based contrast agent administration. Radiology2018;
287:452–460.
30.
KinnerSSchubertTBBruceRJ, et al.
Deep brain nuclei T1 shortening after gadobenate dimeglumine in children: influence of radiation and chemotherapy. AJNR Am J Neuroradiol2018;
39:24–30.
31.
PozegPForgetJMeuliRA, et al.
Age, but not repeated exposure to gadoterate meglumine, is associated with T1- and T2-weighted signal intensity changes in the deep brain nuclei of pediatric patients. Invest Radiol2019;
53:215–222.
32.
FloodTFBhattPRJensenA, et al.
Age-dependent signal intensity changes in the structurally normal pediatric brain on unenhanced T1-weighted MR Imaging. AJNR Am J Neuroradiol2019;
40:1824–1828.
33.
RadbruchAHaaseRKickingerederP, et al.
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. Radiology2017;
283:828–836.
34.
LeeJYParkJEKimHS, et al.
Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: multifactorial analysis in 385 patients. PLoS ONE2017;
12:e0183916.
35.
RamalhoJSemelkaRCAlObaidyM, et al.
Signal change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide. Eur Radiol2016;
26:4080–4088.
