title: Diagnosis of nephrogenic systemic fibrosis by means of elemental bioimaging and speciation analysis.
abstract: The combined use of elemental bioimaging and speciation analysis is presented as a novel means for the diagnosis of nephrogenic systemic fibrosis (NSF), a rare disease occurring after administration of gadolinium-based contrast agents (GBCA) for magnetic resonance imaging (MRI), in skin samples of patients suffering from renal insufficiency. As the pathogenesis of NSF is still largely unknown particularly with regard to the distribution and potential retention of gadolinium in the human organism, a skin biopsy sample from a suspected NSF patient was investigated. The combination of inductively coupled plasma mass spectrometry (ICP-MS), laser ablation (LA) ICP-MS for quantitative elemental bioimaging, and hydrophilic interaction liquid chromatography (HILIC) ICP-MS for speciation analysis allowed one to unambiguously diagnose the patient as a case of NSF. By means of ICP-MS, a total gadolinium concentration from 3.02 to 4.58 mg/kg was determined in the biopsy sample, indicating a considerable deposition of gadolinium in the patient's skin. LA-ICP-MS revealed a distinctly inhomogeneous distribution of gadolinium as well as concentrations of up to 400 mg/kg in individual sections of the skin biopsy. Furthermore, the correlation between the distributions of phosphorus and gadolinium suggests the presence of GdPO4 deposits in the tissue section. Speciation analysis by means of HILIC-ICP-MS showed the presence of the intact GBCA Gd-HP-DO3A eight years after the administration to the patient. The concentration of the contrast agent in the aqueous extract of the skin biopsy was found to be 1.76 nmol/L. Moreover, evidence for the presence of further highly polar gadolinium species in low concentrations was found.
authors.affiliation: †University of Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Birka
authors.affiliation: †University of Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany.
authors.forename: Kristina S
authors.initials: KS
authors.lastname: Wentker
authors.affiliation: §Johannes Wesling Klinikum Minden, Hautklinik, Hans-Nolte Straße 1, 32429 Minden, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Lusmöller
authors.affiliation: §Johannes Wesling Klinikum Minden, Hautklinik, Hans-Nolte Straße 1, 32429 Minden, Germany.
authors.forename: Brigit
authors.initials: B
authors.lastname: Arheilger
authors.affiliation: †University of Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Wehe
authors.affiliation: †University of Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany.|‡European Virtual Institute for Speciation Analysis (EVISA), Mendelstraße 11, 48149 Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sperling
authors.affiliation: §Johannes Wesling Klinikum Minden, Hautklinik, Hans-Nolte Straße 1, 32429 Minden, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stadler
authors.affiliation: †University of Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D003287:Contrast Media / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry; D005260:Female; D019786:Gadolinium DTPA / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry; D057054:Molecular Imaging; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010758:Phosphorus / Q000378:metabolism; D012867:Skin / Q000473:pathology; D012995:Solubility; D014867:Water / Q000032:analysis
chemical_list: D003287:Contrast Media; D014867:Water; D010758:Phosphorus; D019786:Gadolinium DTPA; D002118:Calcium