Monitoring of Autologous Chondrocyte Implantation by 3T-MR

Articular cartilage injury is the most frequent result of traumas. During the last years, surgical therapy of articular cartilage defects has been continuously developed. Nowadays, autologous transplantation of cartilage using biomaterials is accepted as a very promising method. This development, together with increasing number of cartilage repair surgery, require a reliable, objective and possibly non-invasive technique for post-operative follow up. MR imaging was shown to be a reliable technique for morphological evaluation of cartilage defects and cartilage- repair tissue. Together with the high resolution morphologic visualization of a cartilage repair tissue, analysis of the cartilage matrix is also necessary as it reflects mechanical load-bearing capacity of cartilage. For high resolution imaging, optimized protocols and high-field (3.0T) MR scanners are necessary. Contrast-enhanced techniques as well as sodium MR imaging have been proven to be useful in in vitro and in vivo examinations for selective visualization of proteoglycans, which represent one of the basic components of the cartilage matrix. These techniques were developed in our working group within two Jubiläum fund projects (funded by Austrian National Bank). The structure of the collagen fibres seems to be selectively monitored by T2-Mapping and diffusion-weighted MR imaging. As we have shown in another Jubiläum fund project, the measurement of T1rho relaxation times in surgically untreated cartilage will bring no significant difference compared to T2 mapping. However, this technique may provide advantages in studies of cartilage transplants. In the near future, the described biochemically selective MR methods should be used in practice for examining transplants of cartilage cells (chondrocytes) on various carriers (collagen membranes, collagen gel, derivatives of hyaluronic acid), both in vitro in cultures and in vivo in patients. Such examinations enable high resolution follow up studies and quantification of morphological as well as biochemical development of cartilage transplants. This MR follow up of the maturation progress should replace arthroscopically biopsy used so far. Moreover, it could be useful in evaluating newly developed cartilage transplants and in optimizing rehabilitation programmes in general and also individually for each subject.

In addition to morphological-anatomical analysis of repair tissue after cartilage defect treatment by different techniques from simple drilling of the bone to fill the cartilage defect by a blood clot, which then develops into fibrous tissue to more sophisticated cell-based transplantation techniques we could develop a so called biochemical Magnetic Resonance Imaging (MRI) of repair tissue after cartilage repair surgery. For this biochemical MR either existing methods in MR were optimized or further developed for clinical use or new MR methods were developed. These MR techniques comprised as `biochemical MR` allows to follow-up and monitor the maturation of repair tissue in patients after cartilage repair surgeries over several years. We have termed it `biochemical MR imaging` which should define the change from conventional morphological-anatomical MR imaging to MR imaging and quantification of the ultra structural composition of tissues such as cartilage and cartilage repair tissue. Using biochemical MR of cartilage we were able to monitor the development of the components of cartilage and their organization over time, such as the collagen fiber network, which is part of the cartilage integrity and we could define a marker which allows us to define if an organization of this collagen fiber network could be achieved. This was possible by MR techniques such as T2 mapping, T2* mapping and Magnetization Transfer Contrast which are relatively specific for collagen fiber content and organization. In addition we could visualize and quantify another component of cartilage, the content of glycosaminoglycan in cartilage repair tissue compared to normal cartilage over time. We know that after cell-based cartilage transplantation techniques the implanted cells produce components of the matrix of cartilage. Since glycosaminoglycans are responsible for the biomechanical properties of cartilage their amount in repair tissue is critical for the mechanical properties of the repair tissue. This component could be visualized by techniques such as dGEMRIC, sodium imaging and CEST. Based on these developments we were able to evaluate the quality of repair tissue after different cartilage repair surgeries and could move from pure morphological anatomical analysis to noninvasive quality control of the efficacy of cartilage repair surgeries. This information could only be gained so far from biopsies. Therefore our MR techniques will significantly reduce the number of invasive arthroscopies and biopsies Based on the promising results of biochemical MR in cartilage repair tissue, we have transferred these techniques to other diseases such as osteoarthritis and rheumatoid arthritis. In osteoarthritis cartilage degeneration and in particular a focal loss of glycosaminoglycans represents the earliest stage of disease and provides the chance to detect degeneration at a stage where disease-modifying drugs may stop or even reverse the course of the disease. Furthermore, we have now shifted the application of biochemical MR to other structures of the joint such as the menisci, the tendons, and most recently the cruciate ligaments. We have moved forward from the joints to the spine, where the intervertebral discs (IVD) are well suited for biochemical MR, since the IVD is very similar to the composition of articular cartilage and shows very similar biochemical and biomechanical properties.