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

7T 多成分 T1rho/T2 软骨蛋白含量的 MRI 评估

• 批准号: 8546680
• 负责人: Cory R. Wyatt
• 金额: $ 5.39万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546680
• 关键词: Acceleration; Adult; Age; American; Area; Binding; Biochemical; Bovine Cartilage; Calcified; Cartilage; Cattle; Chemicals; Clinical; Collagen; Collagen Fiber; Creatine; Data; Data Quality; Data Set; Degenerative polyarthritis; Detection; Development; Early Diagnosis; Enzymes; Feasibility Studies; Future; Generations; Glutamates; Human; Image; Image Analysis; Individual; Knee; Knee Osteoarthritis; Learning; Life Expectancy; Magnetic Resonance Imaging; Measurement; Measures; Medical; Meniscus structure of joint; Morphologic artifacts; Motion; Noise; Obesity; Occupations; Patients; Prevention; Proteins; Proteoglycan; Public Health; Radial; Relaxation; Reporting; Research; Resolution; Retirement; Sampling; Scanning; Sepharose; Signal Transduction; Site; Spatial Distribution; Staging; Structural Protein; Structure; Testing; Time; Tissues; Validation; Water; Work; absorption; articular cartilage; bone; cost; design; disability; human tissue; improved; in vivo; knee replacement arthroplasty; novel; novel diagnostics; novel marker; public health relevance; research study; tool; volunteer

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.

描述（由申请人提供）：我们建议开发一种新型 7 特斯拉 UTE-T1rho 磁共振成像（MRI）序列，它将提供软骨浅层、深层和钙化层中 T1rho 和 T2 的多指数测量。 T1rho 弛豫值与软骨中的蛋白多糖浓度相关，而 T2 弛豫已被证明与胶原纤维结构相关。使用 7 特斯拉成像将实现更高的信噪比和可能更高的分辨率，从而有可能提高 T1rho 测量的准确性。此外，T1rho 灵敏度将增加到 7 特斯拉，从而有可能检测更小的变化。目标 1 将重点开发 3 特斯拉和 7 特斯拉的组合 UTE-T1rho 序列。初步工作将集中于将各个 UTE 和 T1rho 序列从 3 特斯拉转换为 7 特斯拉。然后，这些序列将在 3 Tesla 下组合，以学习挑战性较小的应用的经验教训。最后，在 3 Tesla 中吸取的经验教训将用于结合 7 Tesla 中的序列。在目标 2 中，目标 1 中开发的序列将在模型、牛软骨和人类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 T1rho 和 UTE 测量。将使用组合序列对来自 6-18 个月牛膝盖的切除软骨样本进行成像，并检查多指数 T1rho/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，来自接受全膝关节置换术的患者的人类软骨样本将使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，将进行20名志愿者的可行性研究，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。志愿者将平均分为四组。第 1 组将由 20-35 岁之间的健康对照组成，第 2 组将由 Kellgren-Lawrence (KL) 评分为 0 的志愿者（35-60 岁）组成，第 3 组将由 KL=1- 的志愿者组成。第 2 组（轻度 OA），第 4 组将由 KL=3-4（重度 OA）的志愿者组成。第 1 组的志愿者将在 3 特斯拉和 7 特斯拉时使用组合序列进行成像，而其他组将仅在 7 特斯拉时进行成像。将检查所有志愿者的多指数 T1rho/T2 值。相关性 目前，3 特斯拉的 T1rho 成像被用作 OA 早期阶段软骨中蛋白多糖损失的标记。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（例如深层和钙化层）进行 T1rho 测量。此外，开发的序列将允许对 T1rho 和 T2 值进行多指数拟合，可能为软骨退化提供新的标记。所有这些改进也将有可能改进对由于骨关节炎发作而引起的软骨生化变化的检测。