Editorial comment: the future of compositional MRI for cartilage
Editorial comment: the future of compositional MRI for cartilage
Thomas M. Link 0 1
0 Department of Radiology of Biomedical Imaging, University of California , 400 Parnassus Ave, A-367, San Francisco, CA 94143 , USA
1 Thomas M. Link
This editorial comment refers to the article: BDetection of early cartilage damage: feasibility and potential of gagCEST imaging at 7T^ by Brinkhof et al, Eur Radiol 2018. MRI-based cartilage compositional biomarkers, where do we stand? Currently, one of the most promising new cartilage imaging biomarker candidates is gagCEST imaging, which allows mapping the glycosaminoglycan (GAG) concentration in cartilage. The first feasibility study was published in 2008 by Ling et al.  and showed that by exploiting the exchangeable protons of GAG it was possible to measure localized GAG concentrations in bovine patella samples. Subsequently, the technique has been used in a number of studies [7-9], mostly at 7T. Concerns were raised about using the technology at 3 T, and in their experimental study Singh et al. concluded that gagCEST is not expected to lead to accurate quantification of GAG content in healthy or degenerated cartilage at 3 T . However, the investigators conceded that the technique holds promise as a clinically viable technique at 7T.
In 1997, Dardzinski et al. published one of the first studies
quantifying cartilage T2 in young asymptomatic volunteers
], thus establishing the concept of compositional cartilage
imaging. Over the next 20 years, new MRI-based techniques
were developed, and the techniques were validated and
investigated in clinical research studies. To date, the best
established compositional imaging biomarkers are T2 and
T1rho relaxation time mappings. It has been shown that
compositional biomarkers can assess the mechanical properties of
], predict focal cartilage breakdown [
] and also
provide a risk assessment concerning the development of
radiographic OA [
In addition to T1rho and T2, other compositional biomarkers
have been developed, which include delayed
gadoliniumenhanced MRI of cartilage (dGEMRIC), T2* imaging,
sodium imaging, glycosaminoglycan chemical exchange
saturation transfer imaging (gagCEST), diffusion-weighted imaging
and diffusion tensor imaging. Some of these candidates,
however, are unlikely to be used clinically, such as dGEMRIC
(there was a recent Federal Food and Drug Administration
warning concerning gadolinium storage in the body and brain
for months to years) and sodium imaging (dedicated coils are
required, and there is a low signal-to-noise ratio).
What does the current study tell us
In this issue of European Radiology, Brinkhof et al. use
gagCEST at 7T in volunteers and patients before cartilage
repair surgery to show its clinical feasibility [
]. This study
is also a first step to establishing this technique as an imaging
biomarker. Required criteria for biomarkers include
reproducibility, validity and the ability to assess disease burden and
differentiate patients with and without disease, predict risk
for disease and monitor therapy. The investigators developed
a fast 3D gagCEST sequence and demonstrated its
reproducibility, scanning each volunteer two times. They found
excellent reproducibility with coefficients of variation ranging from
2.25% at the lateral condyle to 1.40% at the trochlea. They
also validated the measurements using findings during
cartilage repair surgery as a standard of reference and found a
significantly different GAG effect in damaged cartilage
compared with healthy cartilage at the contralateral condyle.
Where do we go from here?
gagCEST imaging is an exciting novel technique to better
characterize localized GAG concentrations in cartilage. This
study showed in a relatively small sample of subjects that the
3D gagCEST sequence developed by the investigators is
reproducible and can show differences in GAG content between
areas with advanced defects and healthy cartilage. While this
is a promising first step, we have to consider the challenges
and limitations: (1) Imaging at 7T is unlikely to become a
standard clinical tool in the near future, and if this technology
cannot eventually be developed for 3 T, it will likely not be
feasible for larger patient populations, (2) a cartilage
compositional biomarker needs to identify early changes of the
cartilage matrix before focal defects occur, and using advanced
International Cartilage Repair Society grades 3 and 4 lesions
for validation is not a suitable standard of reference, (3)
biomarkers need to be comparable between different machines
and vendors, and (4) we need information on whether it can
predict cartilage loss and monitor therapy. All these issuees
will have to be addressed step-by-step and painstakingly
before gagCEST has a future in compositional cartilage imaging.
While the technique is clearly promising and the presented
data are encouraging, the road ahead is steep and stony.
Funding The authors state that this work has not received any funding.
Compliance with ethical standards
Guarantor The scientific guarantor of this publication is Thomas M.
Conflict of interest The authors of this manuscript declare no
relationships with any companies, whose products or services may be related to
the subject matter of the article.
Statistics and biometry
for this paper.
No complex statistical methods were necessary
Informed consent Written informed consent was not required for this
study because this is an editorial without any study subjects.
Ethical approval Institutional Review Board approval was not required
because this is an editorial without any study subjects.
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