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Variability in hair gadolinium concentrations among decedents who received gadolinium-based contrast agents

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Abstract

This study utilized laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify gadolinium in the hair of autopsy cases that had received gadolinium-based contrast agents (GBCAs) before death. Consecutive autopsy cases were reviewed for GBCA injections and subjects who received a single type of GBCA in the year before death were included. Hair samples were analyzed using LA-ICP-MS as a line scan technique and parameters were optimized to maximize instrument sensitivity, accuracy, and precision. Linear regression analyses between hair measures and gadolinium dose were executed. LA-ICP-MS analysis produced a time-resolved record of GCBA exposure, with the position of the gadolinium peak maxima along the hair shaft providing a good estimate for the day that GBCA injection occurred (R2 = 0.46; p = 0.0022); however, substantial within and between subject variation in the position of the GBCA peak was observed. Average area under the curve for gadolinium peaks in the hair samples was a better predictor of gadolinium dose (R2 = 0.41; p = 0.0046), compared to the average of peak maxima concentration. Correlation between area under the curve and dose suggests that LA-ICP-MS analysis of hair may be an effective method to evaluate gadolinium levels in subjects in vivo after exposure to GBCAs. This study demonstrates that analysis of human hair using techniques with high spatial resolution such as LA-ICP-MS has excellent potential to reveal time-dependent signatures of past exposures.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AAS:

Atomic absorbance spectroscopy

cps:

Counts per second

CV:

Coefficient of variation

eGFR:

Estimated glomerular filtration rate

EMA:

European Medicines Agency

ESI:

Elemental Scientific, Inc.

FDA:

US Food and Drug Administration

GBCA:

Gadolinium-based contrast agent

ICP-MS:

Inductively coupled plasma mass spectrometry

LA-ICP-MS:

Laser ablation inductively coupled plasma mass spectrometry

mm:

Millimeter

Nd:YAG:

Neodymium: yttrium aluminum garnet

NIST:

National Institute of Standards and Technology

NWR:

New Wave Research

SD:

Standard deviation

SRM:

Standard reference material

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Code availability

Data was analyzed using R for the current study and custom codes are available from the corresponding author on reasonable request.

Funding

This work was supported by the National Institute of Environmental Health Sciences (grant number P30ES007033) and in part by a grant from Guerbet, LLC. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Institute of Environmental Health Sciences or Guerbet, LLC.

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Authors and Affiliations

  1. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA

    Brianne R. Duncan, Michael Paulsen & Christopher D. Simpson

  2. Exponent, Inc., Bellevue, WA, 98007, USA

    Brianne R. Duncan

  3. Department of Radiology, University of Washington, Seattle, WA, 98195, USA

    Makoto Hasegawa & Masahiro Kobayashi

  4. Department of Radiology, Toho University Ohashi Medical Center, Tokyo, 153-8515, Japan

    Makoto Hasegawa

  5. Department of Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA

    Desiree A. Marshall & Luis F. Gonzalez-Cuyar

  6. Radiology & Neurological Surgery, University of Washington, Seattle, WA, 98195, USA

    Kenneth R. Maravilla

  7. Magnetic Resonance Research Laboratory, University of Washington, Seattle, WA, 98195, USA

    Kenneth R. Maravilla

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  1. Brianne R. Duncan
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  2. Makoto Hasegawa
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  4. Luis F. Gonzalez-Cuyar
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  5. Michael Paulsen
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  6. Masahiro Kobayashi
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  7. Kenneth R. Maravilla
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  8. Christopher D. Simpson
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Contributions

B. Duncan obtained relevant information, analyzed samples and data, and drafted the manuscript. M. Hasegawa obtained relevant information, provided samples, and contributed to the manuscript. D. Marshall and L. Gonzalez-Cuyar collected samples. M. Paulsen analyzed samples. M. Kobayashi provided samples. K. Maravilla and C. Simpson contributed to the study design and to drafting and editing of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Brianne R. Duncan.

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This study was approved by the University of Washington Human Subjects Review Board for retrospective review of medical records and was Health Insurance Portability and Accountability Act compliant. Autopsy consent from each subject granted authorization for use of tissues for research purposes.

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Duncan, B.R., Hasegawa, M., Marshall, D.A. et al. Variability in hair gadolinium concentrations among decedents who received gadolinium-based contrast agents. Anal Bioanal Chem 413, 1571–1582 (2021). https://doi.org/10.1007/s00216-020-03116-3

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