Synopsis

Quantitative techniques such T2/T2* imaging, sodium MRI and gagCEST help to analyze the composition of the connective tissues

Results from quantitative techniques provide additional information and predictive markers for MSK structures and have the potential for the development of imaging biomarkers.

Highlights

Quantitative MRI of musculoskeletal tissues provides additional compositional information in both clinical and research applications.

Sodium MRI and CEST are promising techniques to replace contrast media-dependent approach for glycosaminoglycan detection in cartilage and tendon.

Multi-component T2/T2* mapping provides deeper information about the collagen fibers organization in connective tissues.

Problem summary

Quantitative biochemical MSK MRI

Compositional (or biochemical) MRI enables detection of biochemical and micro-structural changes in the cartilage extracellular matrix (ECM). Biochemical MRI techniques can be either proteoglycan specific or collagen/water specific. Since the early stages of degeneration are usually accompanied by loss of proteoglycans and collagen matrix decomposition, there is a demand for sensitive non-invasive approaches allowing for analysis of the tissue composition. Further, the resent advances of quantitative MRI of musculoskeletal tissues are described.

T2/T2* mapping

The T2 values in cartilage, tendons, menisci and ligaments reflect water content, collagen content, and collagen fiber orientation in the ECM [1]. In cartilage, the two most widely used applications are predicting the impact of osteoarthritis (OA) [2] and monitoring the status and maturation of cartilage transplants [3]. Preliminary studies at 7 T demonstrate lower T2 values compared with 3 T as expected; however, the laminar variation is also less pronounced at this field strength [4]. Laminar variation (or zonal stratification) is given by cartilage structure with typical collagen orientation (superficial, transitional and deep zone) and was successfully used as a semi-quantitative marker for cartilage transplant monitoring. In tendons, ligaments and menisci, very short T2 limits the usage of T2 mapping for collagen matrix analysis; however, there are short TE techniques available which allow for T2* mapping with similar properties as T2 mapping. First signs of tendinopathy and meniscus degeneration are associated with the collagen fibers decomposition. This can be detected by either mono- or bi-component T2* analysis [5,6]. Furthermore, anatomical MRI of Achilles tendon benefits from ultra-high field due to high resolution which allows to depict the tendon microstructure. T2* mapping of fast-relaxing tissues provides more robust bi-component analysis thanks to high signal acquired at ultra-short TE's.

Sodium Imaging

Noninvasive sodium MR imaging can directly determine the cartilage GAG content, which plays a central role in cartilage homeostasis. New technical developments in the recent decade have helped to transfer this method from in vitro to pre-clinical in vivo studies. The sodium MR sensitivity is only 9% of the proton MR sensitivity, and the sodium in vivo concentration is several thousand times lower than the proton concentration (depending on the type of human tissue). As a consequence, the SNR of sodium MRI is 3000–20 000 times lower (depending on the organ) than the SNR of proton MRI. Moreover, sodium in biological tissues exhibits very short bi-exponential transverse relaxation times T2. Despite of challenging nature of sodium MRI for cartilage evaluation, there have been successfully performed several studies validating sodium MRI as a quantitative marker for cartilage degeneration [7] and monitoring the cartilage transplantation [8]. Also, sodium MRI has been used as a marker for Achilles tendinopathy [9] and treatment monitoring [10] .

gagCEST imaging

Chemical exchange saturation transfer (CEST) is an MRI technique that enables the quantification of chemical exchange processes between protons bound to solutes and surrounding bulk water molecules [11]. Since the introduction of the gagCEST method, studies have been performed on patient and volunteer subjects at field strengths of 3 T and 7 T, respectively, to explore the potential of the technique for clinical use. These studies clearly demonstrated the usefulness of the technique to assess the cartilage GAG content at 7 T [12]. To validate and evaluate the potential of the gagCEST technique as a biomarker for GAG content in cartilage, Schmitt and colleagues compared sodium imaging with gagCEST in five patients who had undergone microfractures (MFX) and seven who had undergone matrix-associated chondrocyte transplantation (MACT) [13]. A strong correlation between sodium and gagCEST values demonstrated the sensitivity of this method to GAG content in native cartilage and repair tissue.

Acknowledgements

References

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