Distribution and chemical forms of gadolinium in the brain: a review

Kanda, Tomonori; Nakai, Yudai; Hagiwara, Akifumi; Oba, Hiroshi; Toyoda, Keiko; Furui, Shigeru

doi:10.1259/bjr.20170115

Cited by 53 publications

(35 citation statements)

References 52 publications

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“…Gadolinium accumulation in the brain after multiple intravenous administrations has been a major concern since it was first reported in 2014 (61). However, there have been no reports demonstrating brain toxicity (62); the US Food and Drug Administration and American College of Radiology have declared that there is no evidence to date that gadolinium accumulation in the brain is harmful and that there is no need to restrict its intravenous usage. In the present study, where intrathecal administration of an MRI contrast agent was utilized, no serious adverse events were noted among our study subjects, and at the 4-week MRI follow-up, no evidence of remaining gadobutrol within brain parenchyma or CSF was found (Supplemental Table 5).…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, where intrathecal administration of an MRI contrast agent was utilized, no serious adverse events were noted among our study subjects, and at the 4-week MRI follow-up, no evidence of remaining gadobutrol within brain parenchyma or CSF was found (Supplemental Table 5). Interestingly, gadolinium deposits in brain tissue have recently been attributed to leakage from blood into CSF through the choroid plexus and entrance into the brain from the surface along perivascular spaces (62). In rats, gadolinium concentration has been shown to be higher in CSF than blood 4.5 hours after intravenous distribution and highest in brain after 24 hours (63).…”

Section: Discussionmentioning

confidence: 99%

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Brain-wide glymphatic enhancement and clearance in humans assessed with MRI

Ringstad¹,

Valnes²,

Dale³

et al. 2018

JCI Insight

345

403

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To what extent does the subarachnoid cerebrospinal fluid (CSF) compartment communicate directly with the extravascular compartment of human brain tissue? Interconnection between the subarachnoid CSF compartment and brain perivascular spaces is reported in some animal studies, but with controversy, and in vivo CSF tracer studies in humans are lacking. In the present work, we examined the distribution of a CSF tracer in the human brain by MRI over a prolonged time span. For this, we included a reference cohort, representing close to healthy individuals, and a cohort of patients with dementia and anticipated compromise of CSF circulation (idiopathic normal pressure hydrocephalus). The MRI contrast agent gadobutrol, which is confined to the extravascular brain compartment by the intact blood-brain barrier, was used as a CSF tracer. Standardized T1-weighted MRI scans were performed before and after intrathecal gadobutrol at defined time points, including at 24 hours, 48 hours, and 4 weeks. All MRI scans were aligned and brain regions were segmented using FreeSurfer, and changes in normalized T1 signals over time were quantified as percentage change from baseline. The study provides in vivo evidence of access to all human brain subregions of a substance administered intrathecally. Clearance of the tracer substance was delayed in the dementia cohort. These observations translate previous findings in animal studies into humans and open new prospects concerning intrathecal treatment regimens, extravascular contrast-enhanced MRI, and assessment of brain clearance function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Brain-wide glymphatic enhancement and clearance in humans assessed with MRI

Ringstad¹,

Valnes²,

Dale³

et al. 2018

JCI Insight

345

403

View full text Add to dashboard Cite

show abstract

“…In the past few years, some concern has been raised on the use of intravenous contrast (gadolinium-chelates) given the potential accumulation in basal ganglia of the brain. [28][29][30] However, the use of gadolinium contrast products is part of the routine practice in most institutions and currently recommended in clinical guidelines. 31 The MARIAs can be obtained without the use of gadolinium contrast agents, as the degree of enhancement is not part of the new simplified index.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn’s Disease

et al. 2019

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“…Autopsy studies have shown that gadolinium deposition in the posterior fossa and basal ganglia is not limited to patients with intracranial abnormalities but can also be detected in patients with normal brains at the time of autopsy [17,18]. Several mechanisms of this gadolinium transit and retention in brain regions without impaired BBB have been suggested including active metal transporters [19,20], passage from the cerebrospinal fluid [21][22][23], and brain glymphatic system [24]. The exact mechanism behind the retention, however, remains unsolved.…”

Section: Discussionmentioning

confidence: 99%

Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents

Kiviniemi

Gardberg

et al. 2019

Neuroradiology

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Purpose To quantitate gadolinium deposits in gliomas and adjacent normal brain specimens, and to evaluate their association with tumor contrast enhancement and the type of gadolinium-based contrast agent (GBCA) used. Methods A total of 69 patients with primary glioma who underwent contrast-enhanced magnetic resonance imaging (MRI) prior to surgery were included in this retrospective study. Gadolinium was measured from histologically viable tumor, normal brain, and necrosis within the sample, when available, using inductively coupled plasma mass spectrometry (ICP-MS). Tumor contrast enhancement was categorized as none, minimal, or noticeable. Differences in gadolinium deposits by contrast enhancement and GBCA type were assessed. Results Seven patients received linear GBCA and 62 macrocyclic, respectively. At the time of surgery, gadolinium deposits were detected in 39 out of 69 (57%) tumor samples, 8 out of 13 (62%) normal brain, and 12 out of 14 (86%) necrotic specimens. Gadolinium was detected in both enhancing and non-enhancing tumors, but was greatest in gliomas with noticeable enhancement (p = 0.02). Administration of linear agents gadodiamide and gadopentetate dimeglumine resulted in significantly higher tumor gadolinium relative to macrocyclic gadoterate meglumine (p < 0.01 and p < 0.05, respectively). Normal brain and necrosis also showed higher gadolinium after exposure to linear gadodiamide (both p < 0.05). In multivariate regression, GBCA type (linear/ macrocyclic) was the most powerful predictor of tumor gadolinium retention (p < 0.001). Conclusion Gadolinium can be detected in both enhancing and non-enhancing gliomas, neighboring normal brain, and necrosis. Gadolinium retention is higher after exposure to linear GBCAs compared with the macrocyclic gadoterate meglumine.

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Distribution and chemical forms of gadolinium in the brain: a review

Cited by 53 publications

References 52 publications

Brain-wide glymphatic enhancement and clearance in humans assessed with MRI

Brain-wide glymphatic enhancement and clearance in humans assessed with MRI

Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn’s Disease

Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents

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