Automated Scanning Electron Microscopy and Energy Dispersive x‐ray Spectroscopy (SEM/EDS) for detection and quantification of Gadolinium (Gd) in tissues

Background: Gd, used in MRI contrast agents, is normally not found in biological tissues. It has been associated with an emerging serious dermal and systemic disease, Nephrogenic Systemic Fibrosis (NSF). Methods: We developed automated quantitative SEM/EDS methodology for determination of Gd in skin biopsies of NSF patients. Freshly cut surfaces of paraffin blocks were examined using the variable pressure mode. Standardized conditions and random search of the tissue area allow detection and analysis of higher atomic number features using backscattered electron imaging. Morphology and x‐ray counts per second (cps) for multiple elements, including Gd, were recorded for each feature. We calculated the cps/mm 2 tissue for each element. Results: Gd‐containing features (0.5 to 5 μm diameter) are not uniformly distributed. Their elemental composition (Gd associated with varying percent P, Ca, Na, Fe and Zn) confirms release of free Gd ions from chelated Gd (transmetallation) and its precipitation with PO 4 in tissue. The results were reproducible over a wide range of Gd concentrations from 31 to 4691 cps/mm 2 . Conclusion: This non‐destructive methodology is ideally suited for quantitative identification and distributional analysis of deposits of Gd and co‐precipitated elements in tissue. It supports the etiologic role of Gd in NSF and allows dose‐response analysis at the histologic level. Departmental support.