Quantitative UTE MR Imaging: Sensitive Biomarkers for Osteoarthritis

7.摘要 磁共振成像（MRI）被广泛用于晚期骨关节炎（OA）的诊断，但 对早期OA的诊断不敏感。在早期评估方面有三个主要障碍， OA。首先，OA是一种“整体器官疾病”，涉及所有主要的膝关节组织。然而，许多组织 或组织成分如深层软骨、韧带、腱和骨具有短的 T2和常规临床序列显示很少或没有信号。第二，不同的质子群，即 水质子和大分子质子存在于大多数关节组织中。在许多高分子质子 膝关节组织，尤其是短T2组织尚未进行临床序列研究。 第三，过去二十年的广泛研究集中在OA的两种特定生物标志物：T2和T3。 T1对胶原降解敏感，T2对蛋白聚糖（PG）消耗敏感。主要 混杂因素是魔角效应，当使用本品时，可能导致T2和T1间期增加数倍。 组织纤维定向到B 0场的约54 °。这往往远远超过了疾病带来的变化。 我们开发了3D超短回波时间（UTE）序列，TE短至8 µs， 时间比临床序列的TE短。这些使我们能够直接对“MR不可见”关节组织进行成像。 最近，绝热自旋锁成像已被提出来测量T1 π。磁化传递（MT）成像 已经被引入来评估大分子质子。最重要的是，绝热T1和MT生物标志物 对魔角不敏感在该提议中，我们将进一步开发3D绝热-UTE-T1 cDNA序列，用于 魔角不敏感的T1间期测量，以及魔角不敏感的生物标志物的UTE-MT序列， MT比率（MTR）和MT建模的大分子馏分和交换率。我们将进一步评估 3D绝热-UTE-T1示踪和UTE-MT技术用于评估 正常膝关节标本的短T2和长T2组织（目的1）。我们期望UTE-绝热-T1 生物标志物将对PG消耗敏感，而UTE MTR和MT建模参数将敏感 PG和胶原蛋白的变化。然后，我们将比较新型3D UTE和临床 用于定量评价正常（n=20）、轻度（n=20） 中度（n=20）OA（Aim 2）。我们预计，UTE-adiabatic-T1 UWB和UTE-MT序列将更接近于 对主要膝关节组织的退化敏感。最后我们 将应用3D UTE-adiabatic-T1 MRI和UTE-MT技术评估健康人膝关节退行性变 前交叉韧带（ACL）术后6个月、1年和2年的志愿者（n = 20）和患者（n=20） 重建我们将MR测量与临床评分相关联（目标3）。我们希望UTE措施 对于ACL重建后患者膝关节的变化，将比临床MRI测量更敏感。 该研究可能对早期OA诊断和监测疾病进展产生重大影响。

7. Abstract Magnetic resonance imaging (MRI) is widely used for the diagnosis of advanced osteoarthritis (OA), but is less sensitive for the diagnosis of early OA. There are three major barriers to progress in evaluation of early OA. First, OA is a “whole organ disease” involving all the principal knee joint tissues. However, many tissues or tissue components such as the deep layers of cartilage, menisci, ligaments, tendons and bone have short T2s and show little or no signal with conventional clinical sequences. Second, distinct proton groups, namely water protons and macromolecular protons are present in most joint tissues. Macromolecular protons in many the knee joint tissues, especially the short T2 tissues have not been investigated with clinical sequences. Third, extensive research over the past two decades has focused on two particular biomarkers for OA: T2 and T1, with T2 sensitive to collagen degradation, and T1 sensitive to proteoglycan (PG) depletion. The main confounding factor is the magic angle effect, which may result in a several fold increase in T2 and T1 when the tissue fibers are oriented ~54 to the B0 field. This often far exceeds the change produced by disease. We have developed 3D ultrashort echo time (UTE) sequences with TEs as short as 8 µs that are 100-1000 times shorter than the TEs of clinical sequences. These allow us to directly image “MR invisible” joint tissues. Recently adiabatic spin-lock imaging has been proposed to measure T1. Magnetization transfer (MT) imaging has been introduced to assess macromolecular protons. Most importantly, the adiabatic T1 and MT biomarkers are magic angle insensitive. In this proposal, we will further develop a 3D adiabatic-UTE-T1 sequence for magic angle insensitive T1 measurement, and a UTE-MT sequence for magic angle insensitive biomarkers of MT ratio (MTR) and MT modeling of macromolecular fractions and exchange rates. We will further evaluate the 3D adiabatic-UTE-T1 and UTE-MT techniques for evaluation of macromolecules and water components in both short and long T2 tissues in normal knee joint specimens (Aim 1). We expect that the UTE-adiabatic-T1 biomarker will be sensitive to PG depletion, while the UTE MTR and MT modeling parameters will be sensitive to PG and collagen changes in the knee joint tissues. Then we will compare the novel 3D UTE and clinical sequences for quantitative evaluation of cadaveric human knee specimens with normal (n=20), mild (n=20) and moderate (n=20) OA (Aim 2). We expect that the UTE-adiabatic-T1 and UTE-MT sequences will be more sensitive to degeneration in the principal knee joint tissues than conventional clinical sequences. Finally, we will apply 3D UTE-adiabatic-T1 and UTE-MT techniques to evaluate knee joint degeneration in healthy volunteers (n=20) and patients (n=20) 6 months, 1 year, and 2 years after anterior cruciate ligament (ACL) reconstruction. We will correlate the MR measures with clinical scores (Aim 3). We expect the UTE measures will be more sensitive than clinical MRI measures to changes in the knee of patients after ACL reconstruction. The study is likely to have a major impact on making early OA diagnosis and monitoring disease progression.