Imaging of the Zone of Calcified Cartilage Using 2D and 3D DIR UTE Sequences

描述(申请人提供)：骨关节炎(OA)使数百万人虚弱，是全球医疗保健系统的巨大负担。骨性关节炎是一种以关节软骨和软骨下骨的完整性改变为特征的疾病。关节软骨具有层状结构，可分为四个区，即浅表区、过渡区、放射区和钙化软骨区。传统的磁共振成像主要集中在软骨的三个表面区，通常由于技术原因而忽略了ZCC。ZCC是一个高度修饰的关节软骨矿化区域，形成了软骨和骨之间的重要界面。这是一个在办公自动化领域可能会发生巨大变化的地区。ZCC可能是反应性的，并逐渐钙化邻近的未矿化的软骨，这可能通过增加未钙化的软骨上的力梯度而导致随后的软骨变薄，导致对软骨的进一步破坏。因此，对ZCC早期和晚期改变的研究对于阐明骨关节炎的结构和功能发病机制可能是至关重要的。除了少数例外，我们几乎所有关于骨性关节炎中ZCC的形成、发育成熟、老化和变化的知识都来自于显微技术的应用。ZCC的无创性成像和量化将是非常可取的补充。CT在软骨成像中的作用有限，没有显示ZCC的证据。传统的磁共振(MR)脉冲序列不能对横向弛豫时间(T2)很短的ZCC进行成像。因此，ZCC的MR特性，如反映胶原结构分子水平变化的T2和已被证明与软骨浅层蛋白多糖(PG)耗竭(OA的早期迹象)相关的T1，实际上是未知的。在这项计划中，我们希望开发2D和3D双重绝热反转恢复(DIR)准备的超短回波时间(UTE)脉冲序列，其TES短至8 S，比常规临床序列短100-1000倍，以选择性地显示ZCC。使用两个长的绝热反转脉冲，分别将长T2水(如软骨较浅区域的水)和脂肪均匀地反转和置零，以便产生ZCC的高对比度可视化。其次，我们希望通过将DIR UTE与适当的制备和测量脉冲相结合来开发定量技术来评估ZCC的MR特性，包括T1、T2*、T2和T1。最后，我们希望以定量组织学为金标准，从定性和定量两个方面评价DIR UTE序列在显示ZCC病变方面的作用。40例身体标本中，5例正常，35例轻、中度OA。DIR UTE序列可以非侵入性地评估以前“看不见”的ZCC在OA中的参与，提供有关ZCC在疾病不同阶段中所扮演角色的定量MR信息，并可能实现对OA的早期诊断。 公共卫生相关性：本项目的目标是使用2D和3D DIR UTE序列定性和定量评估正常人体身体标本(n=5)和轻至中度骨关节炎(n=35)的软骨钙化区域，并将DIR UTE MR结果与定量组织学分析相关联。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) debilitates millions of people and is a tremendous burden on health care system worldwide. OA is a condition characterized by changes to the integrity of articular cartilage and subchondral bone. Articular cartilage has a layered structure which can be divided into four zones namely the superficial zone, the transitional zone, the radial zone and the zone of calcified cartilage (ZCC). Conventional MR imaging focuses on the three superficial zones of cartilage, and generally disregards the ZCC for technical reasons. The ZCC is a highly modified mineralized region of articular cartilage that forms an important interface between cartilage and bone. It is a region that may change dramatically in OA. The ZCC may be reactive and progressively calcify adjacent unmineralized cartilage, and this may contribute to subsequent cartilage thinning by increasing the gradient of force across the uncalcified cartilage, leading to further damage to the cartilage. Thus study of early and late alterations to the ZCC may be of critical importance in elucidating the structural and functional pathogenesis of OA. With minor exceptions, almost all of our knowledge about the formation, development maturation, aging, and changes in the ZCC in the setting of OA has come from the application of microscopic techniques. Noninvasive imaging and quantification of the ZCC would be a highly desirable supplement to this. CT has limited role in the imaging of cartilage and shows no evidence of the ZCC. Conventional magnetic resonance (MR) pulse sequences are unable to image the ZCC which has a very short transverse relaxation time (T2). As a consequence, the MR properties of the ZCC, such as its T2 which reflect molecular level changes in collagen structure, and T1 which has been shown to correlate with proteoglycan (PG) depletion (an early sign of OA) in the superficial zones of cartilage, are virtually unknown. In this proposal, we wish to develop both 2D and 3D dual adiabatic inversion recovery (DIR) prepared ultrashort echo time (UTE) pulse sequences with TEs as short as 8 s, which is 100-1000 times shorter than those available with conventional clinical sequences, to selectively visualize the ZCC. Two long adiabatic inversion pulses are employed to uniformly invert and null long T2 water (such as these in the more superficial zones of cartilage) and fat, respectively, in order to produce high contrast visualization of the ZCC. Secondly, we wish to develop quantitative techniques to evaluate the MR properties of the ZCC, including T1, T2*, T2 and T1 by combining DIR UTE with appropriate preparation and measurement pulses. Finally, we wish to evaluate the DIR UTE sequences both qualitatively and quantitatively for depicting lesions in the ZCC in 40 human cadaveric patella samples (5 normal patellae, 35 patellae with mild to moderate OA) using quantitative histology as a gold standard. The DIR UTE sequences may make it possible to non-invasively assess the involvement of the previously MR "invisible" ZCC in OA, provide the quantitative MR information about the role of ZCC in different phases of the disease and may allow early diagnosis of OA. PUBLIC HEALTH RELEVANCE: The goal of this project is to qualitatively and quantitatively evaluate the zone of calcified cartilage of normal human cadaveric patella specimens (n=5) and patellae with mild to moderate OA (n=35) using 2D and 3D DIR UTE sequences, and correlate the DIR UTE MR findings with quantitative histological analysis.