Visualization of biomechanics of articular cartilage by MRI

MRI is widely accepted as a non-invasive technique for visualizing the morphology of healthy and damaged or degenerate articular cartilage. In order to visualize early pathological changes of in vivo cartilage, use of parameter selective MR imaging is combined with relaxation time and diffusion constant mapping makes it possible for the first time to perform a biochemical evaluation of cartilage in vivo. As well as assessing the biochemical properties, it is important to assess the biomechanical properties of cartilage, to make a full functional assessment of articular cartilage, this is particularly important in cartilage implants. The aim of this project is to further develop and validate individual MR parameters for evaluating biomechanical properties of cartilage, in particular cartilage stiffness. In order to fore fill the aims of this project we propose a 3 phase approach with in vitro, in situ and in vivo studies. MRI techniques including T1 and T2 relaxation time mapping; diffusion measurements; and sodium MRI will evaluate cartilage under controlled mechanical loading. The parameters measured in normal and degenerative cartilage using MRI and will be correlated to the results of biochemical, histological and biomechanical tests. In vivo MRI studies of the biochemical and biomechanical properties of articular cartilage and cartilage implants require the application of controlled reproducible loads throughout the range of movement; therefore, as part of the project we will develop an MRI compatible kinematic device. For the planned MR visualization of the biomechanical properties of cartilage, optimal 3D segmentation and 3D reconstruction techniques of the cartilage layers must be developed. Image analysis will allow dynamic visualization of joint motion as well as determination of quantitative parameters including thickness, volume, surface area and joint contact area under physiological loading. This 3D visualization approach ensures that the evaluation of biochemical and biomechanical properties of articular cartilage can be performed under realistic mechanical loading of the joint. So far, such information has only been available through arthroscopic surgery. Thus, along with the basic science research on the biomechanics of articular cartilage, this non-invasive MR method also offers improved diagnosis, follow-up and rehabilitation of patients with cartilage disorders or implants.

Within this project novel in vivo biomechanical MRI techniques with high (3 Tesla) field MR were developed and implemented, that simulate physiological loading in patients in the MR scanner. This was achieved by in vitro studies using a custom-built MR compatible compression device which allowed to perform compression studies of cartilage specimen in MR in comparison to mechanical loading parameters of the same specimen and histological analysis. Based on these results in vivo studies on volunteers and patients followed using a custom-built MR compatible compression device for the lower leg that allowed reproducible and quantitative loading conditions in vivo. Biomechanical MRI that means biochemical MR with and without loading conditions was made possible through the development of novel biochemical MR methods specific for the visualization and quantification of ultrastructural components of articular cartilage such as glycosaminoglycans collagen fibers and water in the knee joint. Besides this active loading, studies utilizing unloading over time, that means when the patient enters the magnet room for the MR exam, the knee joint is in the loaded condition. After about half an hour lying in the supine position unloading in the articular cartilage takes place which can be measured. The biochemical MR techniques used for biomechanical MR of articular cartilage comprised delayed Gadolinium enhanced MRI of cartilage (dGEMRIC), T2, T2* mapping, diffusion-weighted MRI (DWI) and sodium imaging of joints and could be correlated to the biomechanical properties. For these techniques new developments were made either to reduce scan time (dGEMRIC), increase coverage of the joint (dGEMRIC and T2, T2* mapping, or to increase the robustness of the technique such as DWI or sodium imaging. These techniques in particular T2 mapping and DWI provided the input for new finite element models to simulate the mechanical responses of cartilage under different load. Additionally kinematic studies of the knee joint using the above mentioned device allowed to evaluate cartilage-cartilage contact areas and their influence on biochemical MR parameters in different positions of the knee joint. The results will help in a better understanding of the role of different components of cartilage in the biomechanical effects of loading in vivo noninvasively 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. Furthermore it will help to detect biomechanical risk factors for patients after different cartilage repair surgeries.