New Mexico Geological Society Annual Spring Meeting — Abstracts

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Gadolinium (Gd)-based contrast agents are routine intravenous drugs used for magnetic resonance imaging (MRI). Their widespread use allows for rapid clinical diagnosis and monitoring the progression of a disease. Nevertheless, it has been documented that Gd-based contrast agents remain in the body, forming nanoparticle like deposits that have been linked to nephrogenic systemic fibrosis (NSF), acute kidney injury and other adverse health conditions [1-4].

The presence of Gd-rich nanoparticles has been reported in both human and rodent tissues, exhibiting similar morphologies and aggregation patterns. Consequently, rodent models closely resemble human conditions for investigating the distribution, retention, and extent of accumulation of Gd-based contrast agents throughout the body.

In this work, we investigated the morphology and composition of Gd-rich particulates found in rodent tissue: kidney, heart, and olfactory bulb (brain), using probe-corrected transmission electron microscopy (STEM) and energy dispersive x-ray spectroscopy (EDXS). The use of STEM provides the opportunity to investigate nanoparticles at nearly the atomic level. The samples were collected after a washout period of five days from a mouse subject that received Gadodiamide (Omniscan) via intraperitoneal injection five days a week for four weeks (total of 20 doses of 2.5 mmol.kg^-1). The collected tissue samples were prepared following the protocol in [2] for STEM investigation.

Energy Dispersive X-ray Analysis (EDXS) reveals that all Gd-rich deposits share a similar composition, with Gd being consistently accompanied by O, P, Cl, Si, and Ca, with some variations in the amounts of O and N, depending on the organ observed.

The overall morphology of the deposits showed visible variations in size and degree of aggregation, as illustrated in Figure 1. The nanoparticles found in the kidney tissue exhibited a sea-urchin morphology, which has been previously reported by this group [2]. These aggregates appeared to form through the clumping of Gd-rich strands. Detailed analyses at higher magnifications showed that the strands consisted of clustered atoms. In contrast with deposits found in kidney tissue, the nanoparticles in the heart and olfactory bulb tissue displayed a less compact and fragmented structure. Interestingly, at higher magnifications, isolated and nearly spherical nanoparticulates were seen in the heart and olfactory bulb, which seem to be formed of clustered atoms similar to those observed in kidney tissue.

Although precise quantitative information about the composition of the Gd-clusters is lacking due to the challenges imposed by the samples, the chemical composition appears to be consistent. Additionally, it was observed that the Gd particles are stable. The morphological variations observed among the investigated tissues could be linked to the disintegration of Gd-rich nanoparticles into smaller clustered groups as they are mobilized to other organs. This process could hinder the detection of the retained nanoparticles using conventional imaging methods.

References:

1. 1. Cunningham A et al. Front. Toxicol. (2024) 6, 1-15. https://doi.org/10.3389/ftox.2024.1376587
2. 2. DeAguero J et al. Sci. Rep. (2023) 13, https://doi.org/10.1038/s41598-023-28666-13
3. 3. Aime S and Caravan P. J. Magn. Reson. Imaging (2009) 6,1259-67. https://doi:10.1002/jmri.21969
4. 4. Strzeminska I et al. Invest Radiol. (2022) 5, 283-292. https://doi.org/10.1097/rli.0000000000001054