MRI evaluation of cartilage protein content with multi-component T1rho/T2 at 7T

描述(申请人提供)：我们建议开发一种新的7特斯拉的UTE-T1Rho磁共振成像(MRI)序列，该序列将提供软骨浅层、深层和钙化层的T1Rho和T2的多指数测量。T1松弛值与软骨中蛋白多糖浓度相关，而T2松弛与胶原纤维结构有关。使用7特斯拉成像将允许更高的信噪比和可能更高的分辨率，潜在地提高T1Rho测量的准确性。此外，T1Rho敏感度将在7特斯拉时增加，潜在地允许检测到较小的变化。目标1将专注于开发3特斯拉和7特斯拉的UTE-T1Rho组合序列。最初的工作将集中在将单独的UTE和T1Rho序列从3特斯拉转换到7特斯拉。然后，这些序列将在3特斯拉进行组合，以在挑战较小的应用程序中吸取经验教训。最后，在3特斯拉学到的经验将被用来结合7特斯拉的序列。在目标2中，目标1中开发的序列将在幻影、牛软骨和人软骨实验中得到验证。最初的实验将在具有不同浓度琼脂糖凝胶的模体中进行，以验证序列的T1Rho和UTE测量。对6-18个月的牛膝关节软骨标本的实验将使用组合序列进行成像，并将检查多指数T1RHO/T2值。将进行酶治疗，以帮助将胶原和蛋白多糖的作用分离出来。最后，来自全膝关节置换术患者的人软骨样本将用组合序列进行成像，以确定人体组织中的多指数T1rho/T2值。在目标3中，将对20名志愿者进行可行性研究，以在体内测试和优化组合序列，并为未来的研究提供初步数据。志愿者将被平均分成四组。第一组由20-35岁的健康对照组组成，第二组由Kellgren-Lawrence(KL)评分为0的志愿者(35-60岁)组成，第三组由KL=1-2(轻度骨性关节炎)的志愿者组成，第四组由KL=3-4(重度骨性关节炎)的志愿者组成。第一组的志愿者将在3特斯拉和7特斯拉的组合序列下进行成像，而其他组的志愿者将仅在7特斯拉下进行成像。将检查所有志愿者的多指数T1RHO/T2值。目前，在3特斯拉的T1rho成像被用来作为骨关节炎早期软骨蛋白多糖丢失的标志。这项工作将提高这些测量的灵敏度，并允许在T2较短的软骨区域进行T1Rho测量，例如深层和钙化层。此外，开发的序列将允许对T1RH0和T2值进行多指数拟合，潜在地为软骨退变提供新的标记。所有这些改进也将潜在地允许更好地检测由于骨性关节炎的发病对软骨的生化变化。 与公众健康相关：这项工作将提高测量膝关节软骨T1Rho的灵敏度，并允许在T2较短的软骨区域进行这些测量，例如深层和钙化层。此外，开发的序列将允许对T1RH0和T2值进行多指数拟合，潜在地为软骨退变提供新的标记。所有这些改进也将潜在地允许更好地检测由于骨性关节炎的发病对软骨的生化变化。

DESCRIPTION (provided by applicant): We propose to develop a novel UTE-T1rho magnetic resonance imaging (MRI) sequence at 7 Tesla that will provide multiexponential measures of T1rho and T2 in the superficial, deep, and calcified layers of cartilage. T1rho relaxation values have been correlated with proteoglycan concentration in cartilage, while T2 relaxation has been shown to relate to the collagen fiber structure. The use of 7 Tesla imaging will allow for higher signal to noise ratio and possibly higher resolution, potentially improving the accuracy of T1rho measurement. Additionally, T1rho sensitivity will increase at 7 Tesla, potentially allowing for detection of smaller changes. Aim 1 will focus on development of the combined UTE-T1rho sequence at 3 Tesla and 7 Tesla. Initial work will focus on conversion of individual UTE and T1rho sequences from 3 Tesla to 7 Tesla. The sequences will then be combined at 3 Tesla to learn lessons on a less challenging application. Lastly, the lessons learned at 3 Tesla will be used to combine the sequences at 7 Tesla. In Aim 2, the sequences developed in Aim 1 will be validated in experiments with phantoms, bovine cartilage, and human cartilage. Initial experiments will be performed in phantoms with varying concentrations of agarose to validate the T1rho and UTE measures of the sequences. Experiments in excised cartilage samples from 6-18 month bovine knees will be imaged with the combined sequence and the multiexponential T1rho/T2 values will be examined. Enzyme treatments will be performed to help separate the contributions from collagen and proteoglycans. Lastly, human cartilage samples from patients undergoing total knee replacement will be imaged with the combined sequence to determine multiexponential T1rho/T2 values in human tissue. In Aim 3, a feasibility study of twenty volunteers will be conducted to test and optimize the combined sequences in vivo and provide preliminary data for future studies. The volunteers will be split evenly between four groups. Group 1 will consist of healthy controls between the age of 20-35, Group 2 will consist of volunteers (age 35-60) with a Kellgren-Lawrence (KL) score of 0, Group 3 will consist of volunteers with KL=1-2 (mild OA), and Group 4 will consist of volunteers with KL=3-4 (severe OA). Volunteers in Group 1 will be imaged with the combined sequence at 3 Tesla and 7 Tesla, while the other groups will be imaged only at 7 Tesla. Multiexponential T1rho/T2 values will be examined for all volunteers. Relevance Currently, T1rho imaging at 3 Tesla is used as a marker for proteoglycan loss in cartilage during the early stages of OA. This work will improve the sensitivity of these measurements and allow for T1rho measurements in areas of cartilage with short T2, such as the deep and calcified layers. Additionally, the sequences developed will allow for multiexponential fitting of the T1rho and T2 values, potentially providing new markers for cartilage degeneration. All of these improvements will also potentially allow for improved detection of biochemical changes to cartilage due to the onset of OA. PUBLIC HEALTH RELEVANCE: This work will improve the sensitivity of T1rho measurements of knee cartilage and allow for these measurements in areas of cartilage with short T2, such as the deep and calcified layers. Additionally, the sequences developed will allow for multiexponential fitting of the T1rho and T2 values, potentially providing new markers for cartilage degeneration. All of these improvements will also potentially allow for improved detection of biochemical changes to cartilage due to the onset of OA.