Gadolinium Retention and Clearance in the Diabetic Brain after Administrations of Gadodiamide, Gadopentetate Dimeglumine, and Gadoterate Meglumine in a Rat Model

Wang, Shuting; Hua, Zhengxu; Fan, Dongxiao; Zhang, Xin; Kawaguchi, Ren

doi:10.1155/2019/3901907

Cited by 8 publications

(7 citation statements)

References 39 publications

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“…Perivascular, Gd-containing deposits were also reported in the olfactory bulb of rats treated with linear GBCAs (gadodiamide and gadopentetate) but not the macrocyclic agent gadoterate. 58 Colocation of Gd with P in the vicinity of vessels 35,42 is consistent with the precipitation of Gd in the form of GdPO 4 present in the sea urchin-shaped deposits found. 82 This phenomenon might result from transmetallation with calcium, a metal crucial for the tight regulation of cerebral blood flow at the level of the neurovascular unit.…”

Section: Blood Cerebrospinal Fluid Barrier Access Pathwaysupporting

confidence: 71%

“…1). 27,57,58 To our knowledge, no T 1 signal enhancement has been reported so far in olfactory bulbs in humans or rats. Of note is that the olfactory bulb is about 0.01% of the human brain by volume and 2% of the mouse brain by volume.…”

Section: Organ Levelmentioning

confidence: 86%

“…This suggests that the Gd retained in the brain is also likely to be derived from the blood. Perivascular, Gd‐containing deposits were also reported in the olfactory bulb of rats treated with linear GBCAs (gadodiamide and gadopentetate) but not the macrocyclic agent gadoterate 58 …”

Section: Cns Access Pathways For Gbcas: Certainties and Assumptionsmentioning

confidence: 97%

“…Cellular Level TEM studies associated with spectroscopy techniques for characterization showed the presence of electron-dense Gd deposits in the cerebellum of rats treated with linear GBCAs 11,42,58,60 and in patients. 21,61 Except for two, 42,58 these studies focused on the dentate nucleus or its equivalent in rats, the lateral nucleus. 62 Gd deposits had a spheroid and spiny shape resembling a "sea urchin,"~200-300 nm in diameter with 2-nm-wide spines, located in the interstitial space and close to vascular basement membranes (Fig.…”

Section: Organ Levelmentioning

confidence: 99%

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Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Rasschaert

Weller

Schroeder

et al. 2020

Magnetic Resonance Imaging

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The unexpected appearance of T1 hyperintensities, mostly in the dentate nucleus and the globus pallidus, during nonenhanced MRI was reported in 2014. This effect is associated with prior repeated administrations of gadolinium (Gd)‐based contrast agents (GBCAs) in patients with a functional blood–brain barrier (BBB). It is widely assumed that GBCAs do not cross the intact BBB, but the observation of these hypersignals raises questions regarding this assumption. This review critically discusses the mechanisms of Gd accumulation in the brain with regard to access pathways, Gd species, tissue distribution, and subcellular location. We propose the hypothesis that there is early access of Gd species to cerebrospinal fluid, followed by passive diffusion into the brain parenchyma close to the cerebral ventricles. When accessing areas rich in endogenous metals or phosphorus, the less kinetically stable GBCAs would dissociate, and Gd would bind to endogenous macromolecules, and/or precipitate within the brain tissue. It is also proposed that Gd species enter the brain parenchyma along penetrating cortical arteries in periarterial pial‐glial basement membranes and leave the brain along intramural peri‐arterial drainage (IPAD) pathways. Lastly, Gd/GBCAs may access the brain parenchyma directly from the blood through the BBB in the walls of capillaries. It is crucial to distinguish between the physiological distribution and drainage pathways for GBCAs and the possible dissociation of less thermodynamically/kinetically stable GBCAs that lead to long‐term Gd deposition in the brain. Level of Evidence 5. Technical Efficacy Stage 3.

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Section: Blood Cerebrospinal Fluid Barrier Access Pathwaysupporting

confidence: 71%

Section: Organ Levelmentioning

confidence: 86%

Section: Cns Access Pathways For Gbcas: Certainties and Assumptionsmentioning

confidence: 97%

Section: Organ Levelmentioning

confidence: 99%

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Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Rasschaert

Weller

Schroeder

et al. 2020

Magnetic Resonance Imaging

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“…Consistent with previous studies, our study showed that the amount of retained Gd in mice exposed to linear neutral GBCAs Gd was much higher than that in animals exposed to macrocyclic neutral GBCAs gadoteridol. [33][34][35][36][37] However, in all brain regions in mice treated with gadoterate meglumine, the amount of retained total Gd was significantly higher than that in the control group. After administration of gadoterate meglumine, the total amount of Gd in the brain corresponded entirely to the intact gadoteridol.…”

Section: Discussionmentioning

confidence: 89%

Gadolinium Retention in the Brain of Mother and Pup Mouse: Effect of Pregnancy and Repeated Administration of Gadolinium‐Based Contrast Agents

Yao

Zhang

Shi

et al. 2022

Magnetic Resonance Imaging

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Background: The association of repeated administration of gadolinium-based contrast agents (GBCAs) with the gadolinium (Gd) retention in the brains of mother and fetus remains unclear. Purpose: To investigate the effects of pregnancy and repeated administration of GBCAs on Gd retention in the brains of mother and pup mice. Study type: Cross-sectional cohort toxicity study. Animal Model: From gestational days 16-19, pregnant (n = 48) BALB/c mice. Field Strength: A 9.4 T and fast spin echo sequence. Assessment: Half of the mother mice (n = 24) were killed at postnatal day 1 (P1) for inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM). Besides the ICP-MS and TEM, four pups were randomly selected from each mother and killed at P1 for ultraperformance liquid chromatography mass spectrometry (UPLC-MS) and Nissl staining. Statistical Tests: One-way analysis of variance and unpaired t-test. Results: In the group of gadodiamide, retention of Gd in the brains of pregnant mice was significantly lower than that of nonpregnant mice in the area of the deep cerebellar nuclei (DCN) (10.35 AE 2.16 nmol/g vs. 18.74 AE 3.65 nmol/g). Retention of Gd in the DCN of pups whose mothers were administered gadoterate meglumine was significantly lower than that of pups whose mothers were administered gadodiamide (0.21 AE 0.09 nmol/g vs. 6.15 AE 3.21 nmol/g) at P1. In mice treated with gadodiamide, most of the retained Gd in the brain tissue was insoluble (19.5% AE 9.5% of the recovered amount corresponded to the intact complex in the DCN). Data Conclusion: In different brain areas of the mother and pup mice, the retention of Gd after gadoterate meglumine administration was lower than that of gadodiamide and gadopentetate dimeglumine administration, and almost all the detected Gd in pups' brains was intact soluble GBCAs.

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Ten years of gadolinium retention and deposition: ESMRMB-GREC looks backward and forward

van der Molen,

Quattrocchi,

Mallio

et al. 2023

Eur Radiol

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In 2014, for the first time, visible hyperintensities on unenhanced T1-weighted images in the nucleus dentatus and globus pallidus of the brain were associated with previous Gadolinium-based contrast agent (GBCA) injections and gadolinium deposition in patients with normal renal function. This led to a frenzy of retrospective studies with varying methodologies that the European Society of Magnetic Resonance in Medicine and Biology Gadolinium Research and Educational Committee (ESMRMB-GREC) summarised in 2019. Now, after 10 years, the members of the ESMRMB-GREC look backward and forward and review the current state of knowledge of gadolinium retention and deposition. Clinical relevance statement Gadolinium deposition is associated with the use of linear GBCA but no clinical symptoms have been associated with gadolinium deposition. Key Points • Traces of Gadolinium-based contrast agent-derived gadolinium can be retained in multiple organs for a prolonged time. • Gadolinium deposition is associated with the use of linear Gadolinium-based contrast agents. • No clinical symptoms have been associated with gadolinium deposition.

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Gadolinium Retention and Clearance in the Diabetic Brain after Administrations of Gadodiamide, Gadopentetate Dimeglumine, and Gadoterate Meglumine in a Rat Model

Cited by 8 publications

References 39 publications

Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Gadolinium Retention in the Brain of Mother and Pup Mouse: Effect of Pregnancy and Repeated Administration of Gadolinium‐Based Contrast Agents

Ten years of gadolinium retention and deposition: ESMRMB-GREC looks backward and forward

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