Increased Retention of Gadolinium in the Inflamed Brain After Repeated Administration of Gadopentetate Dimeglumine

Wang, Shuangqing; Hesse, Bernhard; Roman, Marco; Stier, Deborah; Castillo‐Michel, Hiram; Cotte, Marine; Suuronen, Jussi‐Petteri; Lagrange, Adrien; Radbruch, Helena; Paul, Friedemann; Taupitz, Matthias; Schellenberger, Eyk; Sack, Ingolf; Infante-Duarte, Carmen

doi:10.1097/rli.0000000000000571

Cited by 33 publications

(42 citation statements)

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“…[79] Low matrix components were assessed to be 0.5 g (carbon), 0.21 g (oxygen), 0.14 g (hydrogen), and 0.17 g (nitrogen) per cm 3 . [80,81] PyMca was used for descriptive statistics regarding RGB imaging, heat maps, and peak spectra. ImageJ was used for the thresholding of the Ca-maps and for reconstruction of the 3D two-photon excitation images.…”

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confidence: 99%

Metal‐Specific Biomaterial Accumulation in Human Peri‐Implant Bone and Bone Marrow

et al. 2020

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Metallic implants are frequently used in medicine to support and replace degenerated tissues. Implant loosening due to particle exposure remains a major cause for revision arthroplasty. The exact role of metal debris in sterile peri-implant inflammation is controversial, as it remains unclear whether and how metals chemically alter and potentially accumulate behind an insulating peri-implant membrane, in the adjacent bone and bone marrow (BM). An intensively focused and bright synchrotron X-ray beam allows for spatially resolving the multi-elemental composition of peri-implant tissues from patients undergoing revision surgery. In peri-implant BM, particulate cobalt (Co) is exclusively co-localized with chromium (Cr), non-particulate Cr accumulates in the BM matrix. Particles consisting of Co and Cr contain less Co than bulk alloy, which indicates a pronounced dissolution capacity. Particulate titanium (Ti) is abundant in the BM and analyzed Ti nanoparticles predominantly consist of titanium dioxide in the anatase crystal phase. Co and Cr but not Ti integrate into peri-implant bone trabeculae. The characteristic of Cr to accumulate in the intertrabecular matrix and trabecular bone is reproducible in a human 3D in vitro model. This study illustrates the importance of updating the view on long-term consequences of biomaterial usage and reveals toxicokinetics within highly sensitive organs.

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confidence: 99%

Metal‐Specific Biomaterial Accumulation in Human Peri‐Implant Bone and Bone Marrow

et al. 2020

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“…Increased signal intensity within the dentate nucleus and globus pallidus have been confirmed in patients with inflammatory states known to cause BBB breakdown, including radiation, metastasis, meningioma, and multiple sclerosis . Increased deposition of Gd following multiple injections of gadopentetic acid in rats with experimental autoimmune encephalitis was recently reported . Sepsis is a severe systemic inflammatory response to microbial toxins that may result in altered BBB permeability.…”

Section: Discussionmentioning

confidence: 89%

“…It should be stated that the Gd retention by the brain, although higher in LPS‐treated rats that control rats, is of a very low amount, but is the consequence of only a single injection of GBCA. Most animal studies in the literature that report Gd deposition after contrast have addressed cumulative effects of repeated injections . Whole brain tissue was analyzed as 1 volume.…”

Section: Discussionmentioning

confidence: 99%

Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium‐based contrast agent administration in rats with experimental sepsis

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Fernández

Wang

et al. 2019

Magnetic Resonance in Med

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Purpose It is important to identify populations that may be vulnerable to the brain deposition of gadolinium (Gd) from MRI contrast agents. At intervals from 24 hours to 6 weeks following injection of a linear Gd contrast agent, the brain, blood and bone content of Gd were compared between control rats and those with experimental endotoxin‐induced sepsis that results in neuroinflammation and blood–brain barrier disruption. Methods Male rats were injected intraperitoneally with 10 mg/kg lipopolysaccharide. Control animals received no injection. Twenty‐four hours later, 0.2 mmol/kg of gadobenate dimeglumine was injected intravenously. Brain, blood, and bone Gd levels were measured at 24 hours, 1 week, 3 weeks, and 6 weeks by inductively coupled plasma mass spectroscopy. Results Blood Gd decreased rapidly between 24 hours and 1 week, and thereafter was undetectable, with no significant difference between lipopolysaccharide and control rats. Brain levels of Gd were significantly higher (4.29‐2.36‐fold) and bone levels slightly higher (1.35‐1.11‐fold) in lipopolysaccharide than control rats at all time points with significant retention at 6 weeks. Conclusion Experimental sepsis results in significantly higher deposition of Gd in the brain and bone in rats. While blood Gd clears rapidly, brain and bone retained substantial Gd even at 6 weeks following contrast injection.

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“…[25] We assessed between 1.5 to 2.5 μg gadolinium/g tissue in the DCN of the research beagle dog, which would have caused a signal intensity change in MRI. Currently published case reports and research studies describe LA-ICP-MS as a useful tool to measure the quantities of retained gadolinium in human [19,58,59] and rodent tissues [47,60]. Potential risk factors with effect on Gd retention described are ongoing neuroinflammation [60] or primary gliomas [59].…”

Section: Discussionmentioning

confidence: 99%

“…Currently published case reports and research studies describe LA-ICP-MS as a useful tool to measure the quantities of retained gadolinium in human [19,58,59] and rodent tissues [47,60]. Potential risk factors with effect on Gd retention described are ongoing neuroinflammation [60] or primary gliomas [59]. Additionally, any type of inflammation can negatively influence the blood brain barrier permeability [61] and therefore could be potential risk factor for gadolinium retention.…”

Section: Discussionmentioning

confidence: 99%

Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents

et al. 2020

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Objective To determine the effect of a linear gadolinium-based contrast agent (GBCA) on the signal intensity (SI) of the deep cerebellar nuclei (DCN) in a retrospective clinical study on dogs after multiple magnetic resonance (MR) examinations with intravenous injections of gadodiamide and LA-ICP-MS analysis of a canine cerebellum after gadodiamide administration. Animals 15 client-owned dogs of different breeds and additionally 1 research beagle dog cadaver. Procedures In the retrospective study part, 15 dogs who underwent multiple consecutive MR imaging examinations with intravenous injection of linear GBCA gadodiamide were analyzed. SI ratio differences on unenhanced T1-weighted MR images before and after gadodiamide injections was calculated by subtracting SI ratios between DCN and pons of the first examination from the ratio of the last examination. Additionally, 1 research beagle dog cadaver was used for LA-ICP-MS (Laser ablation inductively coupled plasma mass spectrometry) analysis of gadolinium in the cerebellum as an add-on to another animal study. Descriptive and non-parametrical statistical analysis was performed and a p-value of < 0.05 was considered significant. Results No statistically significant differences of SI ratios, between DCN and pons, were detectable based on unenhanced T1-weighted MR images. LA-ICP-MS analyses showed between 1.5 to 2.5 μg gadolinium/g tissue in the cerebellum of the examined dog, 35 months after the last of 3 MRI examination with gadodiamide (two examinations at a dose of 1 x 0.1mmol/kg, last examination at a dose of 3 x 0.05mmol/kg).

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Increased Retention of Gadolinium in the Inflamed Brain After Repeated Administration of Gadopentetate Dimeglumine

Cited by 33 publications

References 100 publications

Metal‐Specific Biomaterial Accumulation in Human Peri‐Implant Bone and Bone Marrow

Metal‐Specific Biomaterial Accumulation in Human Peri‐Implant Bone and Bone Marrow

Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium‐based contrast agent administration in rats with experimental sepsis

Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents

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