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Journal of Electron Microscopy Advance Access originally published online on October 19, 2007
Journal of Electron Microscopy 2007 56(5):181-187; doi:10.1093/jmicro/dfm020
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© The Author 2007. Published by Oxford University Press on behalf of Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Automated Scanning Electron Microscopy and X-Ray Microanalysis for in situ Quantification of Gadolinium Deposits in Skin

Charu Thakral and Jerrold L. Abraham*

Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA

* To whom correspondence should be addressed. E-mail: abrahamj{at}upstate.edu

Gadolinium (Gd) has been identified as a possible causative agent of an emerging cutaneous and systemic fibrosing disorder, nephrogenic systemic fibrosis (NSF), which can cause serious disability and even death. To date, there are only two known associations with this disorder – renal insufficiency and Gd enhanced magnetic resonance imaging (MRI). We developed an automated quantitative scanning electron microscopy (SEM) and Energy dispersive x-ray spectroscopy (EDS) method for Gd in tissue of NSF patients. Freshly cut paraffin block surfaces examined using the variable pressure mode under standardized conditions and random search of the tissue area allow in situ detection and semiquantitative morphometric (volumetric) analysis of insoluble higher atomic number features using backscattered electron imaging. We detected Gd ranging from 1 to 2270 cps/mm2 in 57 cutaneous biopsies of NSF. Gd was associated with P, Ca, and usually Na in tissue deposits. Our method reproducibly determines the elemental composition, relative concentration, and spatial distribution of detected features within the tissue. However, we cannot detect features below our spatial resolution, nor concentrations below the detection limit of our SEM/EDS system. The findings confirm transmetallation and release of toxic Gd ions in NSF and allow dose–response analysis at the histologic level.

Keywords     automated scanning electron microscopy, energy dispersive x-ray spectroscopy, Gadolinium, nephrogenic systemic fibrosis

Received     29 June 2007, accepted 17 July 2007


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