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MRI With Gadolinium-Based Contrast Agents: Practical Help to Ensure Patient Safety
LETTER TO THE EDITOR
MRI With GadoliniumBased Contrast Agents: Practical Help to Ensure Patient Safety Malayeri et al [1] write, “At present, there is no evidence suggesting that gadolinium deposition in the brain alters neurologic function.” Where is the evidence for this statement? Free gadolinium is highly toxic. Even though no clinical implications can be drawn from the reported hyperintensities in the dentate nucleus, globus pallidus, pons, and thalamus, the findings are worrisome. Primum non nocere. We must ensure that we do not confuse the lack of results with safety. The precautionary principle must be prevalent. High signal intensity in the globus pallidus and dentate nucleus may be present on unenhanced T1-weighted MR images of patients with multiple sclerosis (MS) who have undergone a relatively large number of previous gadoliniumbased contrast agent (GBCA) administrations. In the clinical progression of MS, what is the cause of the most serious problem: is it the result of the deposition of gadolinium or the “natural” course of MS? How should the radiology community react?
IMPLICATIONS FOR PATIENT CARE For the patients with MS, it is therefore essential to maintain an MRI log that documents each GBCA administration, with a risk-benefit assessment including clear documentation of date, dose, type of formulation (linear or macrocyclic GBCA), and magnetic field strength (eg, 3- or 1.5-T image acquisition). In addition, recommendations for patients with MS and for physicians
for the use of GBCA during pregnancy and nursing should be included in the log. MRI CD-ROMs with covers should be provided to patients to ensure comparability in follow-up examinations. Case report: 39-year-old female patient with attack-like course of MS for 12 years underwent 21 MRI examinations with GBCAs performed by five radiologists at university clinics, hospitals, MS centers, and practices. No report includes the exact details of the administered GBCAs. The detailed documentation should be obligatory because neural tissue deposition is detectable with as few as four lifetime doses of GBCAs. In the medical history, a patient’s imaging history at other hospitals may be missed, but the patient’s MRI log can be reviewed before GBCA administration. Murata et al [2] collected autopsy tissue samples from 9 patients who underwent contrast-enhanced MRI with only a single agent. Exposure included both macrocyclic and linear GBCAs (five with gadoteridol, two with gadobutrol, one with gadobenate, and one with gadoxetate). The result: gadolinium deposition in normal brain and bone tissue was observed with macrocyclic and linear GBCAs. Bone levels measured 23 times higher than brain levels; bone deposition was detected even in bone collected eight years after GBCA exposure. It is possible that bone matrix may rapidly take up a small fraction of intravenously administered GBCA and act as a reservoir, slowly releasing gadolinium, with subsequent uptake in other tissues. Gadolinium deposition from the macrocyclic GBCA gadobutrol may
ª 2016 American College of Radiology 1546-1440/16/$36.00 n http://dx.doi.org/10.1016/j.jacr.2016.05.007
occur within the human brain after multiple gadolinium contrast administrations [3]. Exposure to GBCAs in extremely high cumulative doses can lead to significant gadolinium deposition in the skin [4]. Rogosnitzky and Branch [5] examined in a review the potential biochemical and molecular basis of gadolinium toxicity. Gadolinium deposition is occurring, and exact documentation of GBCA use can improve care for our patients. Hans-Klaus Goischke, Dr. med Hochwaldstraße 2 D-97769 Bad Brückenau Germany e-mail: [email protected] The author has no conflicts of interest related to the material discussed in this article.
REFERENCES 1. Malayeri AA, Brooks KM, Bryant LH, et al. National Institutes of Health perspective on reports of gadolinium deposition in the brain. J Am Coll Radiol 2016;13:237-41. 2. Murata N, Gonzalez-Cuyar LF, Murata K, 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. In press. 3. Stojanov DA, Aracki-Trenkic A, Vojinovic S, et al. 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;26:807-15. 4. Roberts DR, Lindhorst SM, Welsh CT, et al. High levels of gadolinium deposition in the skin of a patient with normal renal function. Invest Radiol 2016;51:280-9. 5. Rogosnitzky M, Branch S. Gadoliniumbased contrast agent toxicity: a review of know and proposed mechanisms. Biometals. In press. http://dx.doi.org/10.1016/j.jacr.2016.05.007 S1546-1440(16)30315-5
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MRI With GadoliniumBased Contrast Agents: Practical Help to Ensure Patient Safety Malayeri et al [1] write, “At present, there is no evidence suggesting that gadolinium deposition in the brain alters neurologic function.” Where is the evidence for this statement? Free gadolinium is highly toxic. Even though no clinical implications can be drawn from the reported hyperintensities in the dentate nucleus, globus pallidus, pons, and thalamus, the findings are worrisome. Primum non nocere. We must ensure that we do not confuse the lack of results with safety. The precautionary principle must be prevalent. High signal intensity in the globus pallidus and dentate nucleus may be present on unenhanced T1-weighted MR images of patients with multiple sclerosis (MS) who have undergone a relatively large number of previous gadoliniumbased contrast agent (GBCA) administrations. In the clinical progression of MS, what is the cause of the most serious problem: is it the result of the deposition of gadolinium or the “natural” course of MS? How should the radiology community react?
IMPLICATIONS FOR PATIENT CARE For the patients with MS, it is therefore essential to maintain an MRI log that documents each GBCA administration, with a risk-benefit assessment including clear documentation of date, dose, type of formulation (linear or macrocyclic GBCA), and magnetic field strength (eg, 3- or 1.5-T image acquisition). In addition, recommendations for patients with MS and for physicians
for the use of GBCA during pregnancy and nursing should be included in the log. MRI CD-ROMs with covers should be provided to patients to ensure comparability in follow-up examinations. Case report: 39-year-old female patient with attack-like course of MS for 12 years underwent 21 MRI examinations with GBCAs performed by five radiologists at university clinics, hospitals, MS centers, and practices. No report includes the exact details of the administered GBCAs. The detailed documentation should be obligatory because neural tissue deposition is detectable with as few as four lifetime doses of GBCAs. In the medical history, a patient’s imaging history at other hospitals may be missed, but the patient’s MRI log can be reviewed before GBCA administration. Murata et al [2] collected autopsy tissue samples from 9 patients who underwent contrast-enhanced MRI with only a single agent. Exposure included both macrocyclic and linear GBCAs (five with gadoteridol, two with gadobutrol, one with gadobenate, and one with gadoxetate). The result: gadolinium deposition in normal brain and bone tissue was observed with macrocyclic and linear GBCAs. Bone levels measured 23 times higher than brain levels; bone deposition was detected even in bone collected eight years after GBCA exposure. It is possible that bone matrix may rapidly take up a small fraction of intravenously administered GBCA and act as a reservoir, slowly releasing gadolinium, with subsequent uptake in other tissues. Gadolinium deposition from the macrocyclic GBCA gadobutrol may
ª 2016 American College of Radiology 1546-1440/16/$36.00 n http://dx.doi.org/10.1016/j.jacr.2016.05.007
occur within the human brain after multiple gadolinium contrast administrations [3]. Exposure to GBCAs in extremely high cumulative doses can lead to significant gadolinium deposition in the skin [4]. Rogosnitzky and Branch [5] examined in a review the potential biochemical and molecular basis of gadolinium toxicity. Gadolinium deposition is occurring, and exact documentation of GBCA use can improve care for our patients. Hans-Klaus Goischke, Dr. med Hochwaldstraße 2 D-97769 Bad Brückenau Germany e-mail: [email protected] The author has no conflicts of interest related to the material discussed in this article.
REFERENCES 1. Malayeri AA, Brooks KM, Bryant LH, et al. National Institutes of Health perspective on reports of gadolinium deposition in the brain. J Am Coll Radiol 2016;13:237-41. 2. Murata N, Gonzalez-Cuyar LF, Murata K, 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. In press. 3. Stojanov DA, Aracki-Trenkic A, Vojinovic S, et al. 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;26:807-15. 4. Roberts DR, Lindhorst SM, Welsh CT, et al. High levels of gadolinium deposition in the skin of a patient with normal renal function. Invest Radiol 2016;51:280-9. 5. Rogosnitzky M, Branch S. Gadoliniumbased contrast agent toxicity: a review of know and proposed mechanisms. Biometals. In press. http://dx.doi.org/10.1016/j.jacr.2016.05.007 S1546-1440(16)30315-5
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1