Ultrahigh-field (7T) MR of early cartilage degeneration

Osteoarthritis, degenerative joint diseases and articular cartilage injuries are very common, affect a significant proportion of the population of all ages (one in six people in the USA are affected by some form of arthritis) and is reaching epidemic proportions. Following cardiovascular diseases, cartilage diseases are the second most frequent cause of illness however; when measured in days of illness, the cartilage diseases even exceed the cardiovascular diseases. As a result, articular cartilage research is a highly topical research field with very significant practical implications and applications for future patient management and care. Current clinical imaging modalities are unable to reliably diagnose cartilage degeneration prior to the onset of irreversible changes. This is a major obstacle to the development and assessment of new strategies to delay or prevent the onset of disabling osteoarthritis. Multi-parametric magnetic resonance imaging (MRI) can provide information about articular cartilage structure and biochemical integrity. However, conventional MRI techniques, as well as dedicated techniques such as magnetization transfer-weighted imaging have been shown to be inconclusive in detecting early changes in osteoarthritis. As such, evaluation of cartilage microstructural detail through MRI remains elusive. Earliest stages of cartilage degeneration comprise loss of glycosaminoglycans (GAG) and increase in water content. A loss of up to 20% of GAG has been reported to be potentially reversible, otherwise osteoarthritis will irreversible develop. We will explore two strategies for improving the sensitivity and specificity of MRI cartilage evaluation: (1) development and implementation of novel MR methods on high and ultrahigh magnetic field MR (3T and 7T), which are specific for the visualization and quantification of GAG loss (Sodium imaging, novel diffusion-sensitive techniques and GAG-sensitive chemical exchange techniques), and (2) adaptation and optimization of these new MRI technologies for potential clinical use in the diagnosis of early articular cartilage injury and degeneration. This multi-disciplinary translational work will require close collaboration between the University Hospital Basel, and the Medical University of Vienna. Achieving these goals will support to integrate novel imaging science with a clinician-scientist led translational clinical project focused on identification of cartilage injury and disease early enough for potential disease modifying treatment.

Within this project novel in vivo MRI techniques with ultrahigh (7 Tesla) field MR were developed and implemented, that have the potential to visualize and quantify early changes of cartilage degeneration. The loss of glycosaminoglycans (GAG) is considered the earliest stage of cartilage degeneration and thus the onset of osteoarthritis, therefore this stage offers the change of intervention by disease modifying drugs, which may stop or even reverse the degenerative process before irreversible OA occurs. The biochemical MR techniques used for evaluation of this early stage of OA in articular cartilage comprised sodium imaging and Chemical Exchange Saturation Transfer (CEST). For these GAG specific techniques new method developments were necessary to increase the robustness and reproducibility of the technique as well as its sensitivity and specificity for GAG in clinical applications. The modified and optimized MR protocols were validated by specimen studies using histochemical analysis of GAG as the standard of reference using knee as well as ankle joint cadavers. Based on this in vitro validation clinical studies with sodium and gagCEST were performed successfully which are among the first clinical studies in this field. Since GAG as an ultrastructural component of articular cartilage is important for the biomechanical properties of cartilage and other structures in the joint, the results will help in a better understanding of the role of different components of cartilage and help in the detection of the earliest stages of cartilage injury and degeneration and facilitate the development and evaluation of new strategies to delay or prevent the onset of disabling osteoarthritis through early intervention with disease modifying treatments. The success of GAG specific biochemical MR in cartilage has encouraged us to apply these techniques on other knee joint structures such as the menisci, the cruciate ligament and tendon with preliminary results in the detection of early degeneration in these joint structures, too.