Quantitative UTE MR Imaging: Sensitive Biomarkers for Osteoarthritis

描述（由申请人提供）：骨关节炎（OA）的早期阶段与蛋白聚糖（pg）的丢失、胶原基质的分解和含水量的变化有关。磁共振成像（MRI）因其高空间分辨率和优异的软组织对比度而被常规用于OA的诊断。最近的研究重点是建立定量MRI测量（T1、T2、T1r和水含量）与关节软骨生化特性之间的相关性。虽然重点放在软骨的变化上，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，它很可能影响其他组织，并导致整个关节的衰竭。在MRI评估中出现了一个特殊的问题，因为许多关节组织，如半月板、韧带和肌腱的T2s只有几毫秒。因此，与传统的临床自旋回波（SE）或梯度回波（GE）序列相比，它们显示出很少或没有信号，这两种序列的典型回波时间（te）为几毫秒或更长。信号的缺乏意味着很难或不可能准确测量它们的T1、T2、T1r和含水量。此外，水存在于关节组织内的束缚区和自由区室中。结合水组分的T2s较短，通常无法用常规的临床脉冲序列检测到。我们开发了标称te为8¿s的UTE序列，比传统序列的te短100-1000倍，并允许我们检测来自膝关节MR“不可见”组织的水信号。此外，我们还开发了一个自旋锁制备的UTE序列来测量T1r，一个T2制备的UTE序列来测量T2，一个UTE PD序列来测量含水量，以及一个UTE双组分分析来量化膝关节主要组织中束缚水和自由水成分的分数。在本提案中，我们将通过研究顺序酶处理（Aim 1）前后相对正常的尸体髌骨（n=40）和半月板（n=40），评估UTE和临床序列在评估PG消耗以及胶原微结构和含水量变化方面的敏感性。然后，我们将比较UTE和临床序列对外形正常（n=20）以及轻度（n=20）和中度（n=20）疾病的尸体膝关节OA的定量诊断（Aim 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变的模式：正常对照（n=20），有膝关节疼痛风险的OA患者（n=20），轻度OA患者（n=20）和中度OA患者（n=20）。我们将把UTE和常规MR测量与Kellgren-Lawrence、WOMAC、Tegner-Lysholm和IKDC临床评分相关联（Aim 3）。所提出的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系统的方式表征OA。这可能对OA的早期发现、监测疾病进展和评估对治疗的反应产生重大影响。

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.