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

描述（由申请人提供）：我们建议开发一种新型的7特斯拉UTE-T1 rho磁共振成像（MRI）序列，该序列将提供软骨浅表层、深层和钙化层中T1 rho和T2的多指数测量。T1 rho松弛值与软骨中的蛋白多糖浓度相关，而T2松弛已被证明与胶原纤维结构相关。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，可能提高T1 rho测量的准确性。此外，T1 rho灵敏度将在7特斯拉时增加，可能允许检测较小的变化。Aim 1将专注于开发3特斯拉和7特斯拉的UTE-T1 rho组合序列。最初的工作将集中在从3特斯拉到7特斯拉的个别UTE和T1 rho序列的转换。然后，这些序列将在3特斯拉下组合，以在挑战性较小的应用中学习经验教训。最后，3特斯拉的经验教训将用于联合收割机7特斯拉的序列。在目标2中，目标1中开发的序列将在体模、牛软骨和人软骨的实验中得到验证。初始实验将在具有不同浓度琼脂糖的模型中进行，以验证序列的T1 rho和UTE测量。将使用组合序列对来自6-18个月牛膝关节的切除软骨样本进行成像，并检查多指数T1 rho/T2值。将进行酶处理以帮助分离胶原蛋白和蛋白聚糖的贡献。最后，将使用组合序列对来自接受全膝关节置换术的患者的人类软骨样本进行成像，以确定人类组织中的多指数T1 rho/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1组将由20-35岁的健康对照组组成，第2组将由KL评分为0的志愿者（35-60岁）组成，第3组将由KL=1-2（轻度OA）的志愿者组成，第4组将由KL=3-4（重度OA）的志愿者组成。第1组中的志愿者将在3特斯拉和7特斯拉的组合序列下成像，而其他组将仅在7特斯拉下成像。将检查所有志愿者的多指数T1 rho/T2值。相关性目前，在3特斯拉的T1 rho成像被用作OA早期阶段软骨中蛋白聚糖损失的标志物。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（如深层和钙化层）进行T1 rho测量。此外，开发的序列将允许T1 rho和T2值的多指数拟合，可能为软骨退变提供新的标志物。所有这些改进也将潜在地允许改进由于OA发作而对软骨的生化变化的检测。 公共卫生相关性：这项工作将提高膝关节软骨T1 rho测量的灵敏度，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T1 rho和T2值的多指数拟合，可能为软骨退变提供新的标志物。所有这些改进也将潜在地允许改进由于OA发作而对软骨的生化变化的检测。

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.