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

描述（由申请人提供）：骨关节炎（OA）使数百万人衰弱，是全球医疗保健系统的巨大负担。OA是一种以关节软骨和软骨下骨的完整性变化为特征的病症。关节软骨具有分层结构，其可分为四个区，即浅表区、过渡区、放射区和钙化软骨区（ZCC）。传统的磁共振成像主要集中在软骨的三个浅表区域，由于技术原因，通常忽略了ZCC。ZCC是关节软骨的高度修饰的矿化区域，其形成软骨和骨之间的重要界面。这是一个可能在OA中发生巨大变化的区域。ZCC可能是反应性的，并且逐渐钙化邻近的未矿化软骨，并且这可能通过增加跨未钙化软骨的力梯度而导致随后的软骨变薄，从而导致对软骨的进一步损伤。 因此，研究ZCC的早期和晚期改变可能对阐明OA的结构和功能发病机制至关重要。除了少数例外，我们几乎所有关于OA中ZCC的形成、发育成熟、老化和变化的知识都来自显微技术的应用。ZCC的非侵入性成像和定量将是一个非常理想的补充。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）脉冲序列不能对具有非常短的横向弛豫时间（T2）的ZCC成像。因此，ZCC的MR特性，例如其反映胶原结构中分子水平变化的T2和已显示与软骨浅表区中蛋白聚糖（PG）耗竭（OA的早期体征）相关的T1，实际上是未知的。 在该提议中，我们希望开发2D和3D双绝热反转恢复（Dual Advertisement Inversion Recovery，DAI）制备的超短回波时间（UTE）脉冲序列，TE短至8 s，比传统临床序列短100-1000倍，以选择性地可视化ZCC。采用两个长绝热反转脉冲来分别均匀地反转和消除长T2水（诸如软骨的更浅表区域中的水）和脂肪，以便产生ZCC的高对比度可视化。其次，我们希望开发定量技术来评估ZCC的MR特性，包括T1，T2*，T2和T1，通过结合适当的制备和测量脉冲的CNOUTE。最后，我们希望使用定量组织学作为金标准，定性和定量评估CANUTE序列用于描述40例人类尸体髌骨样本（5例正常髌骨，35例轻度至中度OA髌骨）中ZCC的病变。磁共振序列可以无创性地评估以前MR“不可见”的ZCC在OA中的参与，提供关于ZCC在疾病的不同阶段中的作用的定量MR信息，并且可以允许OA的早期诊断。 公共卫生相关性：本研究的目的是利用2D和3D MRI序列对正常人髌骨标本（n=5）和轻度至中度OA髌骨标本（n=35）的钙化软骨区进行定性和定量评价，并将MRI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.