Gadolinium deposition in nephrogenic systemic fibrosis: An examination of tissue using synchrotron x-ray fluorescence spectroscopy
Accepted 23 July 2009. published online 09 November 2009.
Background
Nephrogenic systemic fibrosis is a fibrosing disorder associated with gadolinium (Gd)-based contrast agents dosed during renal insufficiency.
Objective
In two patients, Gd deposition in tissue affected by nephrogenic systemic fibrosis was quantified using inductively coupled plasma mass spectrometry. The presence of Gd was confirmed and mapped using synchrotron x-ray fluorescence spectroscopy.
Results
Affected skin and soft tissue from the lower extremity demonstrated 89 and 209 ppm (μg/g, dry weight, formalin fixed) in cases 1 and 2, respectively. In case 2, the same skin and soft tissue was retested after paraffin embedding, with the fat content removed by xylene washes, and this resulted in a measured value of 189 ppm (μg/g, dry weight, paraffin embedded). Synchrotron x-ray fluorescence spectroscopy confirmed Gd in the affected tissue of both cases, and provided high-sensitivity and high-resolution spatial mapping of Gd deposition. A gradient of Gd deposition in tissue correlated with fibrosis and cellularity. Gd deposited in periadnexal locations within the skin, including hair and eccrine ducts, where it colocalized to areas of high calcium and zinc content.
Limitations
Because of the difficulty in obtaining synchrotron x-ray fluorescence spectroscopy scans, tissue from only two patients were mapped. A single control with kidney disease and gadolinium-based contrast agent exposure did not contain Gd.
Conclusions
Gd content on a gravimetric basis was impacted by processing that removed fat and altered the dry weight of the specimens. Gradients of Gd deposition in tissue corresponded to fibrosis and cellularity. Adnexal deposition of Gd correlated with areas of high calcium and zinc content.
aDermatology, University of Colorado Health Sciences Center, Denver, Colorado
bPathology, University of Colorado Health Sciences Center, Denver, Colorado
cChemistry (Geochemistry), Colorado School of Mines, Golden, Colorado
dBiology, Dartmouth College, Hanover, New Hampshire
eChemistry and Earth Sciences, Dartmouth College, Hanover, New Hampshire
fCenter for Advanced Radiation Sources (CARS), University of Chicago, Chicago, Illinois
Correspondence to: Whitney A. High, MD, MEng, Department of Dermatology, University of Colorado School of Medicine, PO Box 6510, Mail Stop F703, Aurora, CO 80045-0510.
Funding for Dr Brown's participation and for materials used in the study was provided by a mentoring grant from the Women's Dermatology Society. Funding for Dr High's participation in the study was provided by a Career Development Award in Medical Dermatology from the Dermatology Foundation. The X26A beamline is supported by the United States Department of Energy (Geosciences, Grant DE-FG02-92ER14244). No additional funding was needed or accepted.
ABSTRACT