The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure

Abstract

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal–ligand complexes, especially with repeated use, should be studied further.

Iron-Catalyzed Parahydrogen Induced Polarization

“…Para hydrogen ( p -H 2 ), the singlet nuclear spin state of dihydrogen, is an attractive tool to address the problem of low sensitivity intrinsic to nuclear magnetic resonance spectroscopy and imaging techniques through magnetic hyperpolarization via the para hydrogen induced polarization (PHIP) effect . Broadly, PHIP is observed when the incorporation of p -H 2 into a substrate, commonly via ( para )­hydrogenation of an unsaturated carbon–carbon bond mediated by an appropriate catalyst, results in high nuclear spin magnetization and greatly enhanced NMR signals. − This is of particular interest to the development of new magnetic resonance imaging (MRI) contrast agents to circumvent the need for gadolinium-based ones that have come under recent scrutiny. − Additionally, PHIP methods offer an inexpensive and convenient alternative to the clinically established Dynamic Nuclear Polarization (DNP) that constitutes a minimum expenditure of several million USD and persistent consumption of cryogenics . Likewise, the application of PHIP in the study of transition metal complexes and their catalytic activity has enabled the detection of short-lived intermediates in low concentrations that would otherwise be undetectable through conventional NMR spectroscopy. − …”

“… 2 − 4 This is of particular interest to the development of new magnetic resonance imaging (MRI) contrast agents to circumvent the need for gadolinium-based ones that have come under recent scrutiny. 5 − 8 Additionally, PHIP methods offer an inexpensive and convenient alternative to the clinically established Dynamic Nuclear Polarization (DNP) that constitutes a minimum expenditure of several million USD and persistent consumption of cryogenics. 9 Likewise, the application of PHIP in the study of transition metal complexes and their catalytic activity has enabled the detection of short-lived intermediates in low concentrations that would otherwise be undetectable through conventional NMR spectroscopy.…”