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 对早期骨性关节炎的诊断敏感性较低。在早期评估方面有三个主要障碍 骨关节炎。首先，骨性关节炎是一种累及所有主要膝关节组织的“全身性疾病”。然而，许多纸巾 或深层软骨、半月板、韧带、肌腱和骨骼等组织成分较短 T2S，在常规临床序列中信号很少或没有信号。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。大分子质子在许多方面 膝关节组织，尤其是短T2区组织，尚未有临床序列的研究。 第三，在过去的二十年里，广泛的研究集中在两个特定的OA生物标志物上：T2和 T1，T2对胶原降解敏感，T1对蛋白多糖(PG)耗竭敏感。主 混杂因素是魔角效应，这可能导致T2和T1的增加几倍 组织纤维取向约54至B0场。这往往远远超过疾病带来的变化。 我们已经开发出3D超短回波时间(UTE)序列，其TES短至8微米，S为100-1000 时间短于临床序列的TES。这使我们能够直接成像“MR隐形”关节组织。 最近，绝热自旋锁定成像被提出用来测量T1。磁化传递(MT)成像 已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 对魔力角度不敏感。在这个方案中，我们将进一步开发3D绝热-UTE-T1序列，用于 魔角不敏感的T1测量，以及魔角不敏感的生物标志物的UTE-MT序列 MT比率(MTR)和大分子组分和交换率的MT模拟。我们将进一步评估 3D绝热-UTE-T1和UTE-MT技术用于评价大分子和水的组成 正常膝关节标本的短T2和长T2组织(目标1)。我们预计UTE-绝热-T1 生物标志物对PG耗竭敏感，而UTE MTR和MT模拟参数敏感 使膝关节组织中PG和胶原蛋白发生变化。然后我们将新的3DUTE与临床进行比较 正常(n=20)、轻度(n=20)身体膝关节标本的定量评价序列 中度(n=20)骨性关节炎(目标2)。我们预计UTE-绝热-T1和UTE-MT序列将更多 对主要膝关节组织的退行性变比常规临床序列敏感。最后，我们 将应用3D UTE-绝热-T1和UTE-MT技术评估健康人膝关节退行性变 志愿者(n=20)和患者(n=20)前交叉韧带(ACL)术后6个月、1年和2年 重建。我们将把磁共振测量与临床评分联系起来(目标3)。我们期待着UTE的措施 将比临床MRI措施更敏感地反映前交叉韧带重建术后患者膝关节的变化。 这项研究可能会对OA的早期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.