Advanced Cartilage Imaging: Clinical Applications
Michel Crema

Synopsis

Advanced MRI techniques enable evaluation of the biochemical composition of articular cartilage. Compositional MRI techniques have the potential to supplement clinical MRI sequences in identifying cartilage degeneration at an earlier stage than is possible today using morphologic sequences only. Although there is some evidence regarding the relationship with some compositional MRI techniques (mainly T2 mapping, T1rho, and dGEMRIC) with symptoms and progression of disease, additional work is needed to isolate the role of the different compositional MRI techniques in predicting structural and clinical outcomes taking into account feasibility of application, reliability and responsiveness of the different techniques available today.

Abstract

Insensitive imaging outcome measures utilized in osteoarthritis (OA) research may partly be responsible for the failure to develop effective treatments. Magnetic Resonance Imaging (MRI) has tremendously improved evaluation of the OA joint by providing direct visualization of tissue morphology, in particular in cartilage. In addition to the morphological evaluation, several advanced MRI based techniques have been developed to assess the biochemical composition of cartilage, exhibiting great potential to be applied in clinical practice and clinical research. These include relaxometry measurements (T2, T2* and T1rho mapping), sodium imaging, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glyscosaminoglycan specific chemical exchange saturation transfer (gagCEST), diffusion weighted imaging (DWI), the use of ultra-short echo times (TE), and diffusion tensor imaging (DTI). Information regarding the ultrastructure of cartilage gained using these techniques is enhancing our understanding of OA pathophysiology. Furthermore, compositional MRI techniques have the potential to serve both as imaging biomarkers for OA and as quantitative, reproducible, and objective endpoints for OA research.

Numerous clinical studies have utilized T2 mapping, however studies evaluating the association of cartilage T2 measurements with symptoms are sparse. Since cartilage itself is an aneural structure, further studies applying T2 mapping are needed to establish the role of early concomitant changes in the subchondral bone and in the synovium, contributing to pain. The association of cartilage T2 values with risk factors for OA (including age, gender, obesity, and malalignment) on the other hand has been extensively studied. The usefulness of T2 mapping in the detection of grade 1 chondromalacia in the knee assessed by arthroscopy (cartilage softening and swelling without morphologic surface changes) was recently demonstrated, showing a marked increase of sensitivity when adding T2 mapping to the routine MRI protocol. To date, there is moderate evidence that T2 mapping of cartilage predict cartilage loss over time. Clinical studies using T2* mapping to study osteoarthritis are currently scant.

T1rho imaging has been suggested to be more sensitive than T2 mapping for differentiating between normal cartilage and early-stages of OA. The association of cartilage T1rho values with risk factors for OA such as age and malalignment has been reported previously. T1rho demonstrated usefulness in differentiating subjects with patellofemoral pain from controls, and in increasing the diagnostic performance in the detection of early chondropathy using arthroscopy as the reference standard, when morphological assessment of cartilage using routine MRI was unremarkable. To date, there is no strong evidence that T1rho values longitudinally predict morphologic cartilage loss over time.

Although there is no strong evidence on the association of dGEMRIC indices and clinical symptoms, such technique demonstrated usefulness in discriminating the various degrees of OA involvement, in differentiating compartments with vs. without meniscal pathology, and in increasing the diagnostic performance in the detection of chondral lesions when added to routine MRI techniques. To date, there is no strong evidence that longitudinal changes in dGEMRIC over time predict progression of cartilage loss in OA.

Other advanced techniques for cartilage composition assessment are available, including sodium MRI, diffusion MRI, gagCEST, and ultra-short TE imaging. These techniques showed potential in demonstrating early cartilage pathology in some studies, but the clinical relevance of these techniques needs to be demonstrated as there is no strong evidence of associations with symptoms or progression of disease.

Biomechanical loading or physical stress applied to cartilage may alter quantitative composition measurements of cartilage in some techniques, such as T2 mapping, T1rho, and dGEMRIC. This factor needs to be taking into account when interpreting the values or indices in clinical practice. However, to date, there is no consensus on the preparation of subjects or patients regarding sports and physical activity (walking, climbing stairs, etc.) before these undergo compositional MRI.

Furthermore, compositional MR imaging measurements of cartilage may be applied for biochemical assessment after cartilage repair procedures, helping in the assessment of the repair tissue as it matures in comparison with the "native" cartilage. These techniques demostrated usefulness in assessing the quality of the repaired tissue when using different surgical techniques, cross-sectionaly and longitudinally. However, there is no strong evidence of associations with clinical outcomes when applying these advanced techniques in the follow-up of cartilage repair procedures.

In summary, compositional MRI techniques have the potential to supplement clinical MRI sequences in identifying cartilage degeneration at an earlier stage than is possible today using morphologic sequences only. Additional work is needed to define the potential of the different compositional MRI techniques in predicting structural and clinical outcomes taking into account feasibility of application, reliability and responsiveness of the different techniques available today.

Acknowledgements

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Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)