This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Because of their paramagnetic properties, solutions of organic gadolinium complexes and gadolinium compounds are used as intravenous radiocontrast agents to enhance images in medical magnetic resonance imaging. Gadolinium has been used for years in adults and children in the United States, Europe and Japan, without any serious complications in thousands of patients. The FDA declared Gadolinium safe for use in MRI in 1988. However, a few side effects, such as mild headache, nausea and local burning can occur. Caravan and colleagues have recently found that patients with severe kidney dysfunction are susceptible to """"""""nephrogenic systemic fibrosis"""""""" if they get gadolinium based MR contrast. Their results indicate that in human subjects, Gd is particularly rich in the kidney and heart. A fundamental understanding of how Gd interacts with these tissues will be crucial in determining the molecular origin of Gd toxicity in these patients. We believe that surveying Gd in regions of heart and kidney tissue using XANES and EXAFS is the most appropriate first step in this unique experimental opportunity, which could potentially have a large impact on translational research. We wish to determine the local coordination environment of Gd in tissue from autopsy samples and compare these results to likely biological Gd models, such as Gd phosphate, Gd sulfate, and the organic Gd contrast agent. From these data, we will be able to clearly determine if and how the Gd contrast agent is chemically altered in kidney and heart tissue. Changes in Gd coordination and/or oxidation state could potentially lead to the adverse effects observed in the Caravan lab.
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