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Evaluation of an imaging biomarker, Dixon quantitative chemical shift imaging, in Gaucher disease: lessons learned

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Gaucher disease (GD) is the first lysosomal storage disorder for which specific therapy became available. The infiltration of bone marrow by storage cells plays an important part in the pathophysiology of skeletal complications and can be quantified by measurements of bone marrow fat fraction (Ff). Ff measurements by Dixon quantitative chemical shift imaging (QCSI) are standard for the follow-up care of GD patients at the Academic Medical Center. Several criteria should be met in order for these measurements to qualify as an imaging biomarker. These include: 1) The presence of the imaging biomarker is closely coupled or linked to the presence of the target disease or condition; 2) The detection and/or quantitative measurement of the biomarker is accurate, reproducible, and feasible over time, and; 3) The changes measured over time in the imaging biomarker are closely coupled, or linked, to the success or failure of the therapeutic effect and the true end point for the medical therapy being evaluated. This review assesses the use of Ff measurements by QCSI as a biomarker for GD in light of these criteria. In addition potential pitfalls are discussed including: degenerative disc disease; vertebral collapse and infection; haematological malignancies; focal fatty deposits; age; menopause; phase and repositioning errors, and; fat surrounding the basivertebral vein.

QCSI measurements of Ff can be used as an imaging biomarker for GD taking these pitfalls into account. It is one of the first biomarkers, in particular imaging biomarkers, for GD that has been systematically evaluated and could be a valuable tool in clinical trials comparing different treatments or dosing regimens.

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Conflict of interest

Laura van Dussen has received travel reimbursements on two occasions (Genzyme, Protalix). Mario Maas and Carla EM Hollak received reimbursements of travel costs and honoraria for participation in symposia and speakers bureaus from Actelion, Protalix, Genzyme and Shire. All honoraria are donated to research funds at the AMC.

Aart J Nederveen and Erik M Akkerman have nothing to disclose.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal rights

This article does not contain any studies with animal subjects performed by the any of the authors.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, PO box 22660, 1100 DD, Amsterdam, The Netherlands

    L. van Dussen & C. E. M. Hollak

  2. Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    E. M. Akkerman, A. J. Nederveen & M. Maas

Authors
  1. L. van Dussen
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  2. E. M. Akkerman
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  3. C. E. M. Hollak
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  4. A. J. Nederveen
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  5. M. Maas
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Corresponding author

Correspondence to L. van Dussen.

Additional information

Communicated by: Robin Lachmann

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van Dussen, L., Akkerman, E.M., Hollak, C.E.M. et al. Evaluation of an imaging biomarker, Dixon quantitative chemical shift imaging, in Gaucher disease: lessons learned. J Inherit Metab Dis 37, 1003–1011 (2014). https://doi.org/10.1007/s10545-014-9726-3

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  • DOI: https://doi.org/10.1007/s10545-014-9726-3

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