Three-dimensional Ultrashort Echo Time Magnetic Resonance Imaging of Entheses

7.摘要 附着点是肌腱、韧带和关节囊与骨连接的区域。他们是 弹性和刚性组织之间的过渡区，应力集中在这两者之间的交界处 由于其广泛不同的机械性能，附着点很常见 在许多疾病中，包括过度使用综合征、早期骨关节炎（OA）和银屑病 关节病（PsA）。尽管其重要性，附着点炎的评估是困难的。临床检查基于 直接触诊的压痛可能不敏感也不特异。超声波可以显示附着点异常 但取决于操作者。传统的磁共振成像在显示关键组织方面没有帮助 存在于T2*s较短的正常附着点中，显示很少或没有信号。因此，正常的附着点 临床MR成像无法识别。此外，临床MR成像生物标志物如T2（a 胶原的生物标志物）和T1 β（蛋白聚糖或PG的生物标志物）显示出强烈的魔角效应， 当组织纤维朝向B 0场约55 °时，可能导致T2和T1的数倍增加。 我们开发了TE为8 µs的3D超短回波时间（UTE）序列，其TE为100~1000倍 比临床序列的TE短，允许我们对附着点成像。最近的研究表明， 自旋锁定和磁化转移（MT）成像是魔角不敏感的。UTE的组合 和绝热T1 ε可以允许对终点PG变化的魔角不敏感的评估。相结合 UTE和MT可提供水和胶原质子分数的魔角不敏感评价， 汇率表中。UTE-adaptive-T1 MIMO和UTE-MT都需要T1补偿。UTE与实际 翻转角成像（AFI）允许短T2组织的精确T1标测。我们的中心假设是， 利用UTE序列直接成像和量化附着点的能力将为相关性提供新的选择， 是认识疾病变化的重要手段。我们的目标 是使用UTE对PsA患者的肌腱和附着点进行系统和全面的表征。在 目的1我们将开发UTE序列用于评估肌腱中的PG、胶原和水成分， 正常踝关节附着点（n=10）。在目标2中，我们将比较UTE和临床序列的定量 评价踝关节标本无异常（n=20），并建立良好的PsA（n=20）。我们将把 MRI结合组织病理学、PLM、生物化学和生物力学进行测量。在目标3中，我们将应用UTE 正常对照组（n=30），PsA患者无临床明显 附着点炎30例，活动性附着点炎30例。PsA患者将接受肿瘤坏死因子治疗 (TNF)抑制剂，并将在2个月，6个月和12个月再次扫描，以访问纵向变化。我们将 将MR测量与体格检查和患者报告的结局（PRO）相关联。我们预计 UTE MRI测量将与PRO、附着点炎症和亚临床附着点炎高度相关。

7. Abstract Entheses are regions where tendons, ligaments and joint capsules are connected to bone. They are transition zones between flexible and rigid tissues, and stress concentrates at the junction between these two types of tissue as a result of their widely different mechanical properties. Entheses are very commonly involved in many diseases including the overuse syndromes, the early stages of osteoarthritis (OA) and psoriatic arthropathy (PsA). Despite its importance, assessment of enthesitis is difficult. Clinical exam based on tenderness on direct palpation may not be sensitive nor specific. Ultrasound can show enthesial abnormalities, but is operator dependent. Conventional MR imaging has not been helpful in demonstrating the key tissues present in normal entheses which have short T2*s and show little or no signal. As a result normal entheses have not been identifiable with clinical MR imaging. Furthermore, clinical MR imaging biomarkers like T2 (a biomarker of collagen) and T1 (a biomarker of proteoglycan or PG) show strong magic angle effects, which may result in a several fold increase in T2 and T1 when the tissue fibers are oriented ~55 to the B0 field. We have developed 3D ultrashort echo time (UTE) sequences with TEs of 8 µs that are 100~1000 times shorter than the TEs of clinical sequences, allowing us to image entheses. Recent studies show that adiabatic spin-locking and magnetization transfer (MT) imaging are magic angle insensitive. The combination of UTE and adiabatic T1 may allow magic angle insensitive assessment of PG changes in entheses. The combination of UTE and MT may provide magic angle insensitive evaluation of water and collagen proton fractions and exchange rates in entheses. Both UTE-adiabatic-T1 and UTE-MT require T1 compensation. UTE with actual flip angle imaging (AFI) allows accurate T1 mapping of short T2 tissues. Our central hypothesis is that the ability to directly image and quantify the entheses with UTE sequences will provide a new option for correlating structure with mechanical function, and an important method for recognizing change in disease. Our objective is to use UTE for systematic and comprehensive characterization of tendons and entheses in PsA patients. In Aim 1 we will develop UTE sequences for assessment of PG, collagen and water components in tendons and entheses in normal ankles (n=10). In Aim 2 we will compare UTE and clinical sequences for quantitative evaluation of ankle specimens with no abnormality (n=20), and well established PsA (n=20). We will correlate MRI measures with histopathology, PLM, biochemistry and biomechanics. In Aim 3 we will apply UTE sequences to the Achilles tendon enthesis in normal controls (n=30), PsA patients with no clinically evident enthesitis (n=30) and with active enthesitis (n=30). The PsA patients will be treated with tumor necrosis factor (TNF) inhibitors, and will be scanned again at two, six and 12 months to access longitudinal changes. We will correlate the MR measures with physical examination and patient reported outcomes (PROs). We expect that UTE MRI measures will be highly correlated with PROs, enthesial inflammation and subclinical enthesitis.