Quantitative UTE MR Imaging: Sensitive Biomarkers for Osteoarthritis

描述(由申请人提供)：骨关节炎(OA)的早期阶段与蛋白多糖(PG)的丢失、胶原基质的分解和水分含量的变化有关。磁共振成像(MRI)因其高空间分辨率和良好的软组织对比度而被常规用于OA的诊断。最近的研究集中在建立定量MRI测量(T1、T2、T1R和水分含量)和关节软骨生化特性之间的相关性。虽然人们一直强调软骨的变化，但骨性关节炎是一种涉及不同组织的多因素疾病，当一个关节组织恶化时，很可能会影响其他组织，并导致整个关节的失败。在MRI评估中出现了一个特别的问题，因为许多关节组织，如半月板、韧带和肌腱，T2只有几毫秒。因此，与常规的临床自旋回波(SE)或梯度回波(GE)序列相比，它们显示的信号很少或没有信号，这些序列的典型回波时间(TES)为几毫秒或更长。缺乏信号意味着很难或不可能准确地测量它们的T1、T2、T1r和水分含量。此外，水存在于关节组织内的结合和游离室中。结合水成分具有较短的T2，并且通常不能通过传统的临床脉冲序列访问。我们已经开发出标称TES为8°S的UTE序列，其TES比常规序列的TES短100-1000倍，并使我们能够检测到膝关节MR“看不见”的组织中的水信号。此外，我们还开发了自旋锁定准备的UTE序列来测量T1R，T2准备的UTE序列来测量T2，UTE PD序列来测量水分含量，以及UTE双组分分析来量化膝关节主要组织中结合水和自由水组分的比例。在这项建议中，我们将通过研究序贯酶治疗前后相对正常的膝盖骨(n=40)和半月板(n=40)，评估UTE和临床序列在评估PG耗竭以及胶原微结构和水分含量变化方面的敏感性(目标1)。然后，我们将比较UTE序列和临床序列对正常(n=20)的身体膝关节以及轻度(n=20)和中度(n=20)疾病的膝关节骨关节炎的定量诊断(目标2)。最后，我们将在四组人类受试者的横断面评估中描述膝关节退行性变的模式：正常对照组(n=20)、有膝关节疼痛风险但X线片正常的骨关节炎患者(n=20)、轻度骨关节炎患者(n=20)和中度骨关节炎患者(n=20)。我们将UTE和常规MR测量与Kellgren-Lawrence、WOMAC、Tegner-Lysholm和IKDC临床评分相关联(目标3)。拟议工作的成功完成将提供新的机会，以比传统临床脉冲序列更全面和更系统的方式表征骨性关节炎。这可能会对OA的早期发现、监测疾病进展和评估治疗反应产生重大影响。

DESCRIPTION (provided by applicant): The early stages of osteoarthritis (OA) are associated with loss of proteoglycans (PGs), breakdown of the collagen matrix, and change in water content. Magnetic resonance imaging (MRI) is routinely used in the diagnosis of OA because of its high spatial resolution and excellent soft tissue contrast. Recent research has focused on establishing correlations between quantitative MRI measurements (T1, T2, T1r, and water content) and the biochemical properties of articular cartilage. While emphasis has been placed on the changes seen in cartilage, OA is a multifactorial disease involving different tissues and when one joint tissue deteriorates, it is likely to affect others and contribute to failure of the oint as a whole. A particular problem arises in MRI assessment because many joint tissues such as menisci, ligaments and tendons have T2s of only a few milliseconds. As a result they show little or no signal with conventional clinical spin echo (SE) or gradient echo (GE) sequences, which have typical echo times (TEs) of several milliseconds or longer. The lack of signal means that it is difficult or impossible to accurately measure their T1, T2, T1r and water content. Furthermore, water is present in both bound and free compartments within joint tissues. The bound water components have shorter T2s and are usually inaccessible with conventional clinical pulse sequences. We have developed UTE sequences with nominal TEs of 8 ¿s which are 100-1000 times shorter than the TEs of conventional sequences, and allow us to detect water signals from MR "invisible" tissues in the knee joint. In addition we have developed a spin-lock prepared UTE sequence to measure T1r, a T2-prepared UTE sequence to measure T2, a UTE PD sequence to measure water content, and UTE bi-component analysis to quantify the fractions of bound and free water components in the principal tissues of the knee joint. In this proposal, we will evaluate the sensitivity of both UTE and clinical sequences for evaluating PG depletion as well as changes in collagen microstructure and water content by studying relatively normal cadaveric patellae (n=40) and menisci (n=40) before and after sequential enzymatic treatment (Aim 1). Then we will compare UTE and clinical sequences for quantitative diagnosis of OA in cadaveric knees with normal (n=20) appearance as well as mild (n=20) and moderate (n=20) disease (Aim 2). Finally we will characterize patterns of knee joint degeneration in a cross sectional assessment of four groups of human subjects: normal controls (n=20), patients at risk of OA with knee pain but normal radiographs (n=20), patients with mild OA (n=20), and patients with moderate OA (n=20). We will correlate the UTE and conventional MR measurements with Kellgren-Lawrence, WOMAC, Tegner-Lysholm and IKDC clinical scores (Aim 3). Successful completion of the proposed work will provide new opportunities to characterize OA in a much more comprehensive and systematic way than has been possible with conventional clinical pulse sequences. This is likely to have a major impact on early detection in OA, monitoring disease progression, and assessing response to therapy.