Increased signal intensity in the unenhanced T1-weighted magnetic resonance in the brain after repeated administrations of a macrocyclic-ionic gadolinium-based contrast agent



Gadoterate meglumine, Brain, Magnetic resonance imaging, Signal intensity


Aim: Gadoterate meglumine is a macrocyclic-ionic gadolinium-based contrast agent (GBCA) which is using in the magnetic resonance imaging (MRI). This study aims to determine the relationship between the signal intensity (SI) increase in the dentate nucleus (DN), pons (P), globus pallidus (GP), thalamus (T) and use gadoterate meglumine by repeated brain MRI in lung cancer patients.

Methods: The study was designed as a retrospective cohort study. The mean SIs of the DN, P, GP, and T and the cerebrospinal fluid (CSF) were measured in the unenhanced T1-weighted (T1w) images of the first and last MRIs of patients who underwent at least three brain MRI examinations with gadoterate meglumine. DN, P, GP, T SIs were divided by values obtained from CSF to standardize the SI measurements. The DN, P, GP, T SIs and DN/CSF, P/CSF, GP/CSF, T/CSF ratios were compared the first and the last MRI examinations.

Results: Our study revealed significant increases in DN, P, GP, and T SIs (P<0.001, P<0.001, P<0.001 and P=0.024,respectively). DN/CSF, P/CSF, GP/CSF, and T/CSF ratios were also significantly increased (P<0.001, P<0.001, P<0.001 and P=0.022, respectively). The number of examinations had a moderately strong positive correlation with in the DN/CSF ratio and a strong positive correlation with in P/CSF ratio (P<0.001 and P<0.001, respectively). There was a weak positive correlation between MRI intervals and in P/CSF ratio (P=0.037).

Conclusion: Our study suggested an increase in the first and the last MRI in DN, P, GP and T SIs related to the number and intervals of repeated examinations of a brain MRI with gadoterate meglumine among patients with lung cancer.


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Choi JW, Moon WJ. Gadolinium Deposition in the Brain: Current Updates. Korean J Radiol. 2019;20(1):134-47. doi: 10.3348/kjr.2018.0356.

Guo BJ, Yang ZL, Zhang LJ. Gadolinium Deposition in Brain: Current Scientific Evidence and Future Perspectives. Front Mol Neurosci. 2018;20;11:335. doi: 10.3389/fnmol.2018.00335.

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.

Ramalho J, Semelka RC, AlObaidy M, Ramalho M, Nunes RH, Castillo M. Signal intensity change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide. Eur Radiol. 2016;26:4080-88. doi: 10.1007/s00330-016-4269-7.

Flood TF, Stence NV, Maloney JA, Mirsky DM. Pediatric brain: repeated exposure to linear gadolinium-based contrast material is associated with increased signal intensity at unenhanced T1-weighted MR imaging. Radiology. 2017;282:222-28. doi: 10.1148/radiol.2016160356.

Kuno H, Jara H, Buch K, Qureshi MM, Chapman MN, Sakai O. Global and regional brain assessment with quantitative MR imaging in patients with prior exposure to linear gadolinium based contrast agents. Radiology. 2017;283:195-204. doi: 10.1148/radiol.2016160674.

Zhang Y, Cao Y, Shih GL, Hecht EM, Prince MR. Extent of signal hyperintensity on unenhanced T1-weighted brain MR images after more than 35 administrations of linear gadolinium-based contrast agents. Radiology. 2017;282:516-25. doi: 10.1148/radiol.2016152864.

Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedetto-Stojanov D, Ljubisavljevic S. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. Eur Radiol. 2016;26(3):807-15. doi: 10.1007/s00330-015-3879-9.

Kang KM, Choi SH, Hwang M, Yun TJ, Kim JH, Sohn CH. T1 shortening in the globus pallidus after multiple administrations of gadobutrol: assessment with a multidynamic multiecho sequence. Radiology. 2018;287(1):258-266. doi: 10.1148/radiol.2017162852.

Rossi Espagnet MC, Bernardi B, Pasquini L, Figà-Talamanca L, Tomà P, Napolitano A. 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 Radiol. 2017;47(10):1345-52. doi: 10.1007/s00247-017-3874-1.

Radbruch A, Weberling LD, Kieslich PJ, Eidel O, Burth S, Kickingereder P et all. 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.

Layne KA, Dargan PI, Archer JRH, Wood DM. Gadolinium deposition and the potential for toxicological sequelae - A literature review of issues surrounding gadolinium-based contrast agents. Br J Clin Pharmacol. 2018;84(11):2522-34. doi: 10.1111/bcp.13718.

Gulani V, Calamante F, Shellock FG, Kanal E, Reeder SB, International Society for Magnetic Resonance in M. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol. 2017;16(7):564-70. doi: 10.1016/S1474-4422(17)30158-8.

Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol. 2006;17:2359-62. doi: 10.1681/ASN.2006060601.

Semelka RC, Ramalho M, AlObaidy M, Ramalho J1, Gadolinium in Humans: A Family of Disorders. AJR Am J Roentgenol. 2016;207(2):229-33. doi: 10.2214/AJR.15.15842.

White GW, Gibby WA, Tweedle MF. Comparison of Gd(DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol. 2006;41(3):272-8. doi: 10.1097/01.rli.0000186569.32408.95.

Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J, 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. Radiology. 2015;276(1):228-32. doi: 10.1148/radiol.2015142690.

Murata N, Gonzalez-Cuyar LF, Murata K, Fligner C, Dills R, Hippe D, et al. Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function. Invest Radiol. 2016;51(7):447-53. doi: 10.1097/RLI.0000000000000252.

Costa AF, van der Pol CB, Maralani PJ, McInnes MDF, Shewchuk JR, Verma R, et al. Gadolinium Deposition in the Brain: A Systematic Review of Existing Guidelines and Policy Statement Issued by the Canadian Association of Radiologists. Can Assoc Radiol J. 2018;69(4):373-82. doi: 10.1016/j.carj.2018.04.002.

Kwakye G, Paoliello M, Mukhopadhyay S, Bowman A, Aschner M. Manganese-induced parkinsonism and Parkinson’s disease: shared and distinguishable features. Int J Environ Res Public Health. 2015;12(7):7519-40. doi: 10.3390/ijerph120707519.

Robert P, Lehericy S, Grand S, Violas X, Fretellier N, Idée J-M, 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 Radiol. 2015;50(8):473-80. doi: 10.1097/RLI.0000000000000181.

Ryu YJ, Choi YH, Cheon JE, Lee WJ, Park S, Park JE, et al. Pediatric brain: gadolinium deposition in dentate nucleus and globus pallidus on unenhanced T1-weighted images is dependent on the type of contrast agent. Invest Radiol. 2018;53(4):246-55. doi: 10.1097/RLI.0000000000000436.

Lohrke J, Frisk AL, Frenzel T, Schockel L, Rosenbruch M, Jost G, 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 Radiol. 2017;52(6):324-33. doi: 10.1097/RLI.0000000000000344.

Lee JY, Park JE, Kim HS, Kim SO, Oh JY, Shim WH, 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 one. 2017;12(8):e0183916. doi: 10.1371/journal.pone.0183916.

Renz DM, Kumpel S, Bottcher J, Pfeil A, Streitparth F, Waginger M, et al. Comparison of Unenhanced T1-Weighted Signal Intensities Within the Dentate Nucleus and the Globus Pallidus After Serial Applications of Gadopentetate Dimeglumine Versus Gadobutrol in a Pediatric Population. Invest Radiol. 2018;53(2):119-27. doi: 10.1097/RLI.0000000000000419.

Kartamihardja AA, Nakajima T, Kameo S, Koyama H, Tsushima Y. Distribution and clearance of retained gadolinium in the brain: differences between linear and macrocyclic gadolinium based contrast agents in a mouse model. Br J Radiol. 2016;89(1066):20160509. doi: 10.1259/bjr.20160509.

McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 2015;275(3):772-82. doi: 10.1148/radiol.15150025.

Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC. Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation. Invest Radiol. 2014;49(10):685-90. doi: 10.1097/RLI.0000000000000072.

Jost G, Lenhard DC, Sieber MA, Lohrke J, Frenzel T, Pietsch H. 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 Radiol. 2016;51(2):83-9. doi: 10.1097/RLI.0000000000000242.

Frenzel T, Lengsfeld P, Schirmer H, Hutter J, Weinmann HJ. 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.






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How to Cite

Kavak RP, Özdemir M. Increased signal intensity in the unenhanced T1-weighted magnetic resonance in the brain after repeated administrations of a macrocyclic-ionic gadolinium-based contrast agent. J Surg Med [Internet]. 2019 Jul. 29 [cited 2024 Jul. 15];3(7):507-11. Available from: