Knee evaluation under mechanical loading by cones ultrashort echo time MR imaging

摘要： 杰班博士是一名具有多学科背景的博士后研究员，他正在提议一项名为 美国国立卫生研究院“圆锥超短波磁共振成像在机械负荷下评估膝关节功能” K01计划在Christine Chung博士、Samuel Ward博士和酱Du博士的指导下发展成为 独立调查员。应用磁共振技术提高骨关节炎的早期诊断水平 成像(MRI)技术受到三个主要障碍的限制。首先，目前的临床核磁共振技术不能 从短T2组织获取信号，如半月板和深层软骨。第二，最多 可从短T2组织获取信号的超短回声时间(UTE)MRI技术是定向的 很敏感。第三，膝关节核磁共振通常是在休息时对关节进行的，这不完全模拟实际情况 生理条件，特别是负荷方面。最近，我们开发了新的ute-mri技术。 (UTE-Ad-T1ρ和UTE-MT)，不区分方向，专为短扫描而设计 膝关节的T2组织。我们假设在机械载荷应用过程中扫描膝关节 使用这些方向不敏感的技术将揭示关节组织的机械特性，在 翻转有助于区分健康的、早期的和轻度的膝关节骨性关节炎。我们还假设了骨头 重建，以加强对软骨/半月板区域的支持，软骨缺陷，这 补充确认早期骨性关节炎的诊断。建议进行一项研究性研究，主要包括三个方面 具体目的：解剖标本研究、全膝关节身体研究、活体研究。一是加快推进 UTE-MRI技术，然后将研究其在健康和中度骨性关节炎患者中的变化规律 加载/卸载过程中的软骨/半月板标本。我们还将评估支撑骨 标本与载荷作用下软骨/半月板的UTE变化模式进行比较。第二，我们将建设和发展 验证用于身体全膝关节研究的气动加载设置，其目的是评估 在一组加载和卸载步骤下膝盖的变化。然后UTE-MRI在关节中的变异模式 将对装载/卸载过程中的健康、轻度和中度OA组进行调查。第三，我们 将设计和建造一个单独的加载装置来执行体内阶段的研究。我们将确定是否在 早期骨性关节炎患者体内UTE-MRI负荷变化模式明显，如果UTE-MRI/CT可以 检测早期和轻度膝骨关节炎患者的骨骼结构和性能的改善。的可行性。 加速我们的方向不敏感的UTE-MRI技术和我们的技术对 在机械加载应用期间膝关节组织的变化(使用加载装置的初始设计)已经被 我们的初步结果证明了这一点。杰班博士和他的导师钟博士、沃德博士和杜博士设计了 详细的培训计划并组建了一支强大的顾问团队来指导杰尔班博士的职业生涯 发展计划，成为一名独立的调查员。

ABSTRACT: Dr. Jerban is postdoctoral researcher with a multidisciplinary background who is proposing a research entitled “Knee evaluation under mechanical loading by Cones Ultrashort Echo Time MR imaging” through NIH K01 program under the mentorship of Drs. Christine Chung, Samuel Ward, and Jiang Du to develop into an independent investigator. Improving the osteoarthritis (OA) diagnosis at early stage using Magnetic Resonance Imaging (MRI) techniques are limited by three main barriers. First, the current clinical MRI techniques do not acquire signal from short T2 tissues, such as the meniscus and the deep layer of cartilage. Second, most Ultrashort Echo Time (UTE) MRI techniques that can acquire signal from short T2 tissues are orientation sensitive. Third, knee MRI is routinely performed on joints at rest, which incompletely mimics the actual physiological condition, particularly, the loading aspects. Recently, we have developed new UTE-MRI techniques (UTE-Ad-T1ρ and UTE-MT) that are not orientation-sensitive and that are designed specifically for scanning short T2 tissues of the knee. We have hypothesized that scanning knee joints during mechanical load application using these orientation-insensitive techniques will reveal the mechanical properties of the joint tissues, which in turn will help to distinguish between healthy, early stage and mild OA knee joints. We also hypothesized bone remodels in order to enhance the support to cartilage/menisci regions with defected cartilage, which complementarily confirms the early stage OA diagnosis. A research study is proposed to cover three main specific aims: dissected specimens’ study, whole knee cadaveric study, and in vivo study. First, we will accelerate the UTE-MRI techniques and then will investigate their variation patterns in healthy and moderate OA human cartilage/menisci specimens during the loading/unloading process. We will also assess the supporting bone specimens to compare with UTE variation patterns in cartilages/menisci under loading. Second, we will build and verify a pneumatic loading setup for the cadaver whole knee study, which is meant to assess the temporal variation of knees under a set of loading and unloading steps. Then the UTE-MRI variation patterns in joints from healthy, mild OA, and moderate OA groups during the loading/unloading process will be investigated. Third, we will design and build a separate loading device to perform the in vivo phase of the study. We will determine if in vivo UTE-MRI variation pattern under loading are distinct for early stage OA patients, and if UTE-MRI/CT can detect an improved bone structure and properties for early stage and mild OA knees. The feasibility of accelerating our orientation-insensitive UTE-MRI techniques and the significant sensitivity of our techniques to changes in knee tissues during mechanical load application (using an initial design of loading device) have been demonstrated in our preliminary results. Dr. Jerban and his mentors, Drs. Chung, Ward, and Du, have designed a detailed training plan and assembled a strong team of advisors to guide Dr. Jerban through his career development plan towards becoming an independent investigator.