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

描述（由申请人提供）：23 Na MRI：订购钠作为软骨素降解骨关节炎的报告物，影响超过一半的65岁以上人群，并对其生活质量产生显著的负面影响。这也给保健系统带来了相当大的开支。由于软骨是一种由血管、神经和淋巴系统供应不足的组织类型，因此当受损时，它的修复能力非常有限。因此，存在对允许早期检测软骨退化的非侵入性诊断方法的巨大需求。目前的诊断技术依赖于通过常规MRI对比机制（如T1、T2、T1技术（dGEMRIC））检测退行性变化。后一种方法在体内成功应用，但它需要IV注射和显著的延迟和关节运动，以使药剂扩散到软骨组织中。Na 23 MRI为这些研究提供了有希望的补充。已知钠离子与蛋白聚糖结构相关，因此可用作骨关节炎的生化标志物。除了是完全内源性的之外，预计该方法对比简单的蛋白聚糖消耗更复杂的结构变化高度敏感。初步数据已经表明，软骨组织中钠的残余四极偶联在酶耗尽后显示出相当大的增加。为了研究相关钠池在最受控环境中的行为，计划测量（i）蛋白聚糖/胶原蛋白/琼脂糖混合物，（ii）新鲜牛和人软骨样品，以及（iii）蛋白聚糖和胶原蛋白耗尽的软骨样品中的Na NMR参数。本项目的最后一部分旨在将23 Na NMR技术转化为7 T下的23 Na MRI方法。结合先进的23 Na NMR技术，用于确定蛋白多糖和胶原蛋白消耗水平的生化测定，T1将使我们能够建立有序的钠作为软骨组织早期退行性变化的敏感报告。该项目的举措将为创新的四极MRI对比技术奠定基础，该技术可用于诊断早期退行性关节疾病，并可能在早期阶段预测风险人群。 项目总结23 Na MRI：骨关节炎影响超过一半的65岁以上的人口，并对他们的生活质量有显着的负面影响。这也给保健系统带来了相当大的开支。由于软骨是一种由血管、神经和淋巴系统供应不足的组织类型，因此当受损时，它的修复能力非常有限。因此，存在对允许早期检测软骨退化的非侵入性诊断方法的巨大需求。该项目的倡议将形成创新的四极MRI对比技术的基础，可用于诊断早期退行性关节疾病。

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.