Gadolinium deposition in nephrogenic systemic fibrosis: An examination of tissue using synchrotron x-ray fluorescence spectroscopy

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.

Key words: adnexa, calcium, clincopathologic correlation, gadolinium, hypercellularity, mapping, nephrogenic systemic fibrosis, quantification, synchrotron x-ray fluorescence spectroscopy, zinc

Abbreviations used: GBCA, gadolinium-based contrast agent, Gd, gadolinium, ICP-MS, inductively coupled plasma mass spectrometry, MR, magnetic resonance, MRI, magnetic resonance imaging, NSF, nephrogenic systemic fibrosis, SEM/EDS, electron microscopy and energy dispersive spectroscopy, SXRFS, synchrotron x-ray fluorescence spectroscopy