This course part covers the applications of molecular dynamic imaging, or more precisely, MT/CEST, T2, T1rho, adiabatic T1rho and T2rho, and RAFF relaxation times in the musculoskeletal applications. The lectures will briefly cover possible musculoskeletal targets for the methods, focusing mostly on articular cartilage which is most frequently studied and affected in musculoskeletal disorders. Furthermore, the methods will be briefly overviewed with respect to the musculoskeletal application, followed by their potential uses.
Target Audience
Basic scientists and clinicians who desire an introduction to musculoskeletal applications of exchange-based and molecular dynamic imaging methods.Educational Objectives
Purpose
In musculoskeletal disorders, such as osteoarthritis (OA), various tissues including articular cartilage, subchondral bone, menisci, tendons, and ligaments are affected (1). OA primarily affects articular cartilage and the subchondral bone, inducing degeneration of the tissues. In degeneration, different tissue constituents, macromolecules, collagens, interstitial water etc., undergo changes in composition, integrity and content. Specific detection of such changes would enable correct diagnoses and thereby provide appropriate therapeutic indications. MRI methods sensitive and desirably specific to molecular dynamics or to changes in them, would be an obvious choice for assessing OA or other musculoskeletal disorders. To this end, various MRI methods sensitive to molecular dynamics have been proposed and investigated in the musculoskeletal system.Methods and results
Different molecular dynamic sensitive MRI contrasts, such as T2, T1rho, adiabatic T1rho and T2rho, and RAFF relaxation time constants have been proposed as markers for different constituents or properties of articular cartilage (2-14) and meniscus (15,16) and the intervertebral disc (17-19). The methods generally rely on imposing the desired contrast weighting in incremental fashion, which allows subsequent estimation of the respective quantitative parameter. Besides relaxation times, MT/CEST methods, specifically glycosaminoglycan CEST (gagCEST) has received significant interest for specific imaging of the proteoglycan content in cartilage and intervertebral disc (18,20-26). In skeletal muscle, both CEST imaging and relaxation time mapping have been utilized (27-32).
Relaxation time methods have demonstrated variable sensitivities to the properties of articular cartilage; for example, T2 relaxation time has been shown to be very sensitive to the integrity and orientation of the collagen fibers in cartilage, while T1rho relaxation time is sensitive to the collagen orientation, the proteoglycan content and degeneration of the tissue in general, depending on the experimental setup. The fully adiabatic version of T1rho relaxation time has demonstrated similar sensitivities as continuous wave T1rho, however providing improved robustness against B0 or B1 field inhomogeneities. RAFF in the second rotating frame has demonstrated similarity with T2 relaxation time. RAFF can be performed in higher rank rotating frames, but such experiments have not been carried out in cartilage. In the skeletal muscle, however, RAFF in the fourth rank rotating frame provided improved results over the second rank RAFF.
CEST, and more specifically gagCEST has been demonstrated to be very specific to the proteoglycan content in articular cartilage. GagCEST relies on selective saturation of the exchangeable -OH groups resonating at 1ppm from water and assessing the resulting CEST peak by various means of analysis. Via the very specific relation to a major tissue constituent, proteoglycans, gagCEST provides an excellent quantitative probe for assessing status of cartilaginous tissues.
Discussion
Different relaxation time mapping techniques provide relatively high signal-to-noise ratio quantitative imaging techniques for the musculoskeletal tissues. However, the specificity of the relaxation time mapping methods to tissue constituents or properties tends to be sub-optimal. Rotating frame relaxation methods provide sensitivities to biologically important regimes of slow molecular motion that are not directly probed by the laboratory frame relaxation methods T1 and T2. A potential problem especially with the T1rho and T2rho techniques is the increased RF deposition (SAR) to the imaging target due to the long pulses utilized. Adiabatic T1rho offers additional flexibility for SAR management. RAFF relaxation on the other hand relies on fast frequency sweep to generate the locking field and allows for significantly lower RF amplitudes to be used, providing another means of managing SAR.
MT and CEST methods, e.g. gagCEST, generally provide higher specificity to tissue constituents than the relaxation mapping -based methods, but they tend to require longer scan times and provide lower SNR. The methods require sufficient spectral separation and in the case of gagCEST, the -OH peak of interest is very close to water resonance, making the measurement challenging. Higher field strengths provide significant benefits for CEST imaging and the method has been typically applied for proteoglycans only at 7T and higher fields. Furthermore, the analysis of gagCEST peak requires careful calibration of the data, i.e. correction for any B0 shifts.
In conclusion, advanced molecular dynamic sensitive MRI methods are under active development and have a clear promise for the quantitative imaging and assessment of various musculoskeletal tissues. Specific sequences and analysis methods are required, but also the methods are becoming increasingly available.
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