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

描述(申请人提供)：23Na核磁共振成像：作为软骨退化报告的有序钠骨关节炎影响65岁以上人口的一半以上，并对他们的生活质量产生重大负面影响。它还给医疗保健系统带来了相当大的开支。由于软骨是一种组织类型，缺乏血管、神经和淋巴系统的供应，因此当软骨受损时，其修复能力非常有限。因此，对能够及早发现软骨退化的非侵入性诊断方法有巨大的需求。目前的诊断技术依赖于通过传统的MRI对比剂，如T1、T2、T1技术(DGEMRIC)来检测退行性改变。后一种方法在体内得到了成功的应用，但它需要静脉注射，并需要很长时间的延迟和关节锻炼，才能使制剂扩散到软骨组织中。NA23MRI为这些研究提供了一个有希望的补充.已知钠离子与蛋白多糖结构有关，因此可用作骨关节炎的生化标记物。除了完全内源性外，这种方法预计对比简单的蛋白多糖耗尽更复杂的结构变化高度敏感。初步数据已经表明，由于酶的消耗，软骨组织中残留的钠的四极偶联显示出相当大的增加。为了研究相关钠池在最受控制的环境中的行为，计划测量(I)蛋白多糖/胶原/琼脂糖混合物，(Ii)新鲜牛和人软骨样本，以及(Iii)蛋白多糖和胶原缺失软骨样本的Na核磁共振参数。该项目的最后部分旨在将23Na核磁共振技术转化为7T下的23Na MRI方法。结合先进的23Na核磁共振技术、测定蛋白多糖和胶原耗竭水平的生化分析，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灵敏报告。该项目的倡议将形成创新的四极磁共振成像对比技术的基础，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危险人群。 项目摘要23Na MRI：作为软骨退化报告的有序钠骨关节炎影响了超过一半的65岁以上人口，并对他们的生活质量产生了重大的负面影响。它还给医疗保健系统带来了相当大的开支。由于软骨是一种组织类型，缺乏血管、神经和淋巴系统的供应，因此当软骨受损时，其修复能力非常有限。因此，对能够及早发现软骨退化的非侵入性诊断方法有巨大的需求。该项目的倡议将形成创新的四极磁共振成像对比技术的基础，该技术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.