Heejun Kang

Use of a gadolinium-based contrast agent (GBCA) increases the diagnostic utility of MRI by allowing better visualization of the disease process. However, the use of GBCAs is not without risks. GBCAs have been associated with acute adverse reactions, as well as with a rare but serious condition called nephrogenic systemic fibrosis. In 2014, Kanda et al¹ first correlated the degree of T1 hyperintensity in the deep brain structures with the number of previous GBCA administrations. McDonald et al² confirmed that this was due to the presence of gadolinium within the neuronal tissues. What was more concerning was that this phenomenon occurred even in patients with normal renal function and an intact blood-brain barrier.

Recognizing the potential impact on patient safety, our study focused on confirming this finding on a large cohort of 195 patients with secondary-progressive MS. Our results showed that as few as 2 GBCA administrations were enough to show significant T1 hyperintensity in the dentate that persisted for at least 1 year after administration. The degree of increase was related to the location (with the dentate being the most sensitive), the number of GBCA administrations, and the class of GBCA (with linear nonionic having greater deposition than linear ionic GBCAs).

Although the exact clinical ramifications are yet to be elucidated, these findings have gained the attention of the medical community and the public, prompting more judicious use of GBCAs, especially in routine follow-up studies. In 2018, the Consortium of MS Centers released a new MRI guideline that made the use of GBCAs optional for follow-up monitoring to detect subclinical disease activity given that standardized protocols were employed.³ This is supported by recent evidence showing that the use of GBCAs does not necessarily result in a higher sensitivity or change in diagnosis of interval disease progression.⁴ Other potential areas where GBCA administration may be optional include follow-up studies for meningioma and pituitary macroadenoma.

Currently, there remain many unanswered questions on this topic, such as whether gadolinium deposition in the brain leads to any adverse clinical effects. Our research group has attempted to expand on this topic by

evaluating the potential adverse effects of GBCAs on MS progression. Our results showed no findings indicating that GBCA administration resulted in greater clinical worsening in patients with secondary-progressive MS.⁵ However, further research is needed to fully understand the impact of gadolinium deposition in the brain.

References

1. Kanda T, Ishii K, Kawaguchi H, 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. Radiology 2014;270:834–41, 10.1148/radiol.13131669
2. McDonald RJ, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 2015;275:772–82, 10.1148/radiol.15150025.
3. MRI Protocol - Consortium of Multiple Sclerosis Centers (CMSC). https://www.mscare.org/page/MRI_protocol. Accessed October 31, 2019.
4. Eichinger P, Schön S, Pongratz V, et al. Accuracy of unenhanced MRI in the detection of new brain lesions in multiple sclerosis. Radiology 2019;291:429–35, 10.1148/radiol.2019181568.
5. Ackermans N, Taylor C, Tam R, et al. Effect of different doses of gadolinium contrast agent on clinical outcomes in MS. Mult Scler J Exp Transl Clin 2019;5: 2055217318823796, 10.1177/2055217318823796.

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