23Na MRI: Ordered Sodium as a Reporter of Cartilage Degradation

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DESCRIPTION (provided by applicant): 23Na MRI: Ordered Sodium as a Reporter on Cartilage Degradation Osteoarthritis affects more than half of the population above the age of 65 and has a significant negative impact on their quality of life. It also imposes considerable expenses on the health care system. Since cartilage is a tissue type that is poorly supplied by blood vessels, nerves and the lymphatic system, it has a very limited capacity for repair when damaged. Consequently, there is an enormous demand for noninvasive diagnostic methods that allow the early detection of cartilage degradation. Current diagnostic techniques rely on the detection of degenerative changes either via conventional MRI contrast mechanisms, such as T1, T2, T1 technique (dGEMRIC). The latter method is applied successfully in vivo, but it requires IV injection and a significant delay and joint exercise to allow the agent to diffuse into the cartilage tissue. Na 23 MRI provides a promising complement to these studies. Sodium ions are known to associate with proteoglycan structures and can therefore be used as biochemical markers of osteoarthritis. In addition to being completely endogenous, this method is expected to be highly sensitive to more complex structural changes than simple proteoglycan depletion. Preliminary data have already shown that the residual quadrupolar couplings of sodium in cartilage tissue show a sizeable increase upon enzymatic depletion. In order to study the behavior of the associated sodium pool in the most controlled environment, it is planned to measure the Na NMR parameters in (i) proteoglycan/collagen/agarose mixtures, (ii) 23 in fresh bovine and human cartilage samples, and in (iii) proteoglycan and collagen depleted cartilage samples. The last part of the project is designed to translate the 23 Na NMR techniques into 23Na MRI methods at 7T. The combination of advanced 23 Na NMR techniques, biochemical assays for determining proteoglycan and collagen depletion levels, T1 will allow us to establish ordered sodium as a sensitive reporter of early degenerative changes in cartilage tissue. The initiatives of this project will form the basis for innovative quadrupolar MRI contrast techniques, which may be used to diagnose early degenerative joint disease and possibly to predict the risk population at an early stage. PROJECT SUMMARY 23Na MRI: Ordered Sodium as a Reporter on Cartilage Degradation Osteoarthritis affects more than half of the population above the age of 65 and has a significant negative impact on their quality of life. It also imposes considerable expenses on the health care system. Since cartilage is a tissue type that is poorly supplied by blood vessels, nerves and the lymphatic system, it has a very limited capacity for repair when damaged. Consequently, there is an enormous demand for noninvasive diagnostic methods that allow the early detection of cartilage degradation. The initiatives of this project will form the basis for innovative quadrupolar MRI contrast techniques, which may be used to diagnose early degenerative joint disease.