Matthew Alvin

The safety of iodinated and gadolinium-based contrast agents (GBCAs) has been and continues to be a hot topic in all areas of radiology, including neuroradiology. In this edition of the AJNR News Digest, we highlight several recently published articles summarizing the safety of iodine-based and gadolinium-based contrast agents used in neuroimaging. These articles provide a good update as to where we stand currently and help answer questions that patients or technologists may pose to the radiologist prior to proceeding with the imaging examination.

Acute kidney injury (AKI) has a variety of definitions, with some advocating for a 25–50% increase in the serum creatinine value over the baseline value. Others base AKI on an absolute increase in the serum creatinine by 0.3–0.5 mg/dL. The time is also variable, over 2–5 days. No matter the definition, the disease can lead to irreversible renal injury, warranting a risk/benefit approach to selecting patients for contrast-enhanced imaging studies.^1–3

Acute ischemic stroke portends high short-term morbidity and mortality, necessitating rapid and accurate diagnosis and treatment for patients. The current American Heart Association/American Stroke Association algorithm in most centers for patients presenting to the emergency department with signs or symptoms suspicious for stroke is to obtain CTA with perfusion (CTP). If a large-vessel occlusion is present and the patient meets criteria, DSA with endovascular treatment (eg, thrombectomy, thrombolysis, angioplasty/stent placement) will likely be pursued. This exposes the patient to another iodine contrast load. Yet, there is no current consensus guideline for proceeding with CTA/CTP and/or DSA in patients with chronic kidney disease.^4–5

Multiple studies have confirmed that the risk of AKI secondary to CTA/CTP imaging is relatively low.^1–5 Other smaller studies have looked at AKI risk with CTA/CTP followed by DSA. With one of the largest cohorts (n = 181), Jia et al² prospectively demonstrated that CTA/CTP followed by DSA in adults with acute ischemic stroke did not significantly increase the likelihood of AKI. Myung et al⁴ subsequently and retrospectively assessed a similar cohort (n = 601; CTA/CTP followed by DSA) and, as expected, found a higher incidence of AKI in patients with low glomerular filtration rate (GFR) (< 30). More notably, the authors considered other risk factors for AKI in their cohort and determined a higher probability of AKI when the baseline GFR was less than 43. Of the few patients who developed AKI, all eventually recovered renal function within a few days without fatality.

Therefore, as discussed by Li and Partovi,⁵ it is prudent to proceed with endovascular treatment when necessary and regardless of the baseline renal function, given such low risk of AKI. Furthermore, the authors remind us that there is still a great deal of controversy over the true relationship between IV contrast and AKI, with some evidence showing that IV contrast does not cause AKI.

GBCAs are chelated to prevent toxicity, with prior research demonstrating the higher stability (lower risk) of macrocyclic agents versus linear agents.^6–8 Overall, GBCAs have been shown to be quite safe for all patients. Edeklev et al⁷ demonstrated that intrathecal administration of a GBCA is safe for patients, while Enterline et al⁸ showed the safety for use in neonates and infants younger than 2 years.

In 2006, a link between GBCAs and nephrogenic systemic fibrosis (NSF) was identified. Subsequent FDA restrictions for the use of GBCAs based on GFR made the incidence of NSF quite low. To add to the low likelihood of NSF, Kanal et al⁶ retrospectively assessed 860 patients with impaired renal function who received a GBCA and found no evidence of NSF development.

Over the past 5 years, the new concern with GBCAs is deposition of gadolinium in the brain. However, there has been no reported negative impact due to this deposition.^9–10 Retrospective large-cohort studies have shown no association between gadolinium deposition and worsening of neurologic or neuropsychological status. Mallio et al⁹ provide clinicians with a good approach to patient care relative to gadolinium deposition—mainly, to provide strong support that there is no documented clinical risk and substantial agreement by national organizations attesting to this lack of risk. Moreso, evidence exists showing that gadolinium is deposited in even higher concentrations in organs outside the brain without associated detrimental effects.

Together, these articles provide a good understanding of the current state of contrast safety in neuroimaging. To summarize, the risk for AKI and/or long-term morbidity or mortality is low with iodine-based contrast agents, meaning CTA/CTP and DSA should not be delayed when necessary. Similarly, the risk for NSF is low using the current FDA-approved GBCAs and there is no evidence of a detrimental effect related to gadolinium deposition in the brain. For an in-depth look at each paper, and for the authors’ commentary, please see the accompanying write-ups.

References

1. Haq MFU, Yip CS, Arora P. The conundrum of contrast-induced acute kidney injury. J Thorac Dis 2020;12:1721–27
2. Jia ZY, Wang SX, Zhao LB, et al. Risk of acute kidney injury with consecutive, multidose use of iodinated contrast in patients with acute ischemic stroke. AJNR Am J Neuroradiol 2019;40:652–54
3. Weber R, van Hal R, Stracke P, et al. Incidence of acute kidney injury After computed tomography angiography ± computed tomography perfusion followed by thrombectomy in patients with stroke using a postprocedural hydration protocol. J Am Heart Assoc 2020;9:e014418
4. Myung JW, Kim JH, Cho J, et al. Contrast-induced acute kidney injury in radiologic management of acute ischemic stroke in the emergency setting. AJNR Am J Neuroradiol 2020;41:632–36
5. Li X, Partovi S. Save the brain first: CTA and mechanical thrombectomy in patients at risk for contrast-induced nephropathy. AJNR Am J Neuroradiol 2020;41:637–38
6. Kanal E, Patton TJ, Krefting I, et al. Nephrogenic systemic fibrosis risk assessment and skin biopsy quantification in patients with renal disease following gadobenate contrast administration. AJNR Am J Neuroradiol 2020;41:393–99
7. Edeklev CS, Halvorsen M, Løvland G, et al. Intrathecal use of gadobutrol for glymphatic MR imaging: prospective safety study of 100 patients. AJNR Am J Neuroradiol 2019;40:1257–64
8. Enterline DS, Martin KW, Parmar HA, et al. Safety and diagnostic efficacy of gadobenate dimeglumine in MRI of the brain and spine of neonates and infants. AJNR Am J Neuroradiol 2019;40:2001–09
9. Mallio CA, Quattrocchi CC, Rovira À, et al. Gadolinium deposition safety: seeking the patient’s perspective. AJNR Am J Neuroradiol 2020;41:944–46
10. Mallio CA, Rovira À, Parizel PM, et al. Exposure to gadolinium and neurotoxicity: current status of preclinical and clinical studies. Neuroradiology 2020;62:925–34

Image from: Enterline DS, Martin KW, Parmar HA, et al. Safety and diagnostic efficacy of gadobenate dimeglumine in MRI of the brain and spine of neonates and infants.