Ultrashort TE MR Imaging of Femorotibial Cartilage

描述（由申请人提供）： 本研究的总体目的是开发和询问新的MR成像生物标志物与组织学和生物力学参考标准，检测软骨和半月板的结构改变，并应用这些技术表征退行性变的模式，有助于了解膝关节OA的发病机制。提出了四个具体目标（SA）：1）用组织学参考标准验证用于定性关节表征的新型MR脉冲序列，2）用组织学和生物力学参考标准验证检测关节胶原和蛋白聚糖改变的新型MR脉冲序列，3）探索尸体标本中软骨病变和关节病理学的关系，以及4）将MR技术应用于在尿道撕裂的情况下进行保守治疗和尿道切除术的患者群体。这是一项前瞻性研究，将使用尸体膝关节样本执行特定目标1至3。将使用X线片对膝关节样本进行筛选，根据X线片分级确定的重度OA患者将从研究中排除。在具体目标1中，将由3名亚专业肌肉骨骼放射科医生独立使用标准和新型MR脉冲序列进行MRI形态分级。将使用组织学参考标准来确定新序列是否对直肠病变的检测和分类更敏感。我们的零假设是，新的MR序列将更准确地揭示正常的血管基础结构和结构改变。在具体目标2中，我们将比较标准定量MR技术（T2标测、T1 rho评价）与新型定量MR技术（UTE T2* 技术、UTE T1 rho评价），以确定新型序列是否对分别检测椎间盘组织中的胶原蛋白和蛋白聚糖改变更敏感。这一目的将通过对尸体直肠组织进行受控的特异性酶消化来实现。我们将使用沐浴消化液的分析，以及消化组织的组织学和生物力学参考标准。后者将使我们能够确定定量MR数据是否有可能反映组织功能。我们的零假设是新型MR序列对半月板和软骨中胶原蛋白和蛋白聚糖降解的变化更敏感。在具体目标3中，我们将在尸体膝关节标本中建立正常和病理性膝关节炎的定量MR值。此外，我们将确定软骨病变的模式（形态学和定量MR数据）的特点，每种类型的关节病理。我们将实施组织学和生物力学参考标准。我们的零假设是定量MR特性将反映半月板和软骨的最早结构改变，并且软骨损伤的严重程度将与半月板撕裂的类型和严重程度相关。在具体目标4中，我们将在患有尿道撕裂的患者人群中实施新型MR成像序列。将描述尿道撕裂的模式，并对保守治疗和尿道切除术的队列进行纵向随访。将进行与功能临床和活动评分的相关性分析。该项目对临床应用具有令人兴奋的意义。所开发的新型脉冲序列允许用成像生物标志物非侵入性地询问最早的组织结构变化，所述成像生物标志物反映软骨和半月板中的蛋白聚糖和胶原蛋白以及钙化层软骨的完整性。潜在的应用是无限的。虽然目前的研究重点是OA，在全国残疾的主要原因，仅次于心血管疾病，这些技术可以应用于影响组织结构的任何过程（变性，创伤，风湿病），允许组织基础设施的非侵入性MR评价，指导临床治疗，确定结构改变的进展，以及对治疗的反应。

DESCRIPTION (provided by applicant): The general purpose of the study is to develop and interrogate novel MR imaging biomarkers with histologic and biomechanical reference standards that detect structural alteration in cartilage and meniscus and to apply these techniques for characterization of patterns of degeneration that aid in understanding pathogenesis of knee OA. Four specific aims (SA) are proposed: 1) validation of novel MR pulse sequences for qualitative meniscal characterization with a histologic reference standard, 2) validation of novel MR pulse sequences that detect meniscal collagen and proteoglycan alteration with histologic, and biomechanical reference standards, 3) exploration of the relationship of cartilage lesions and meniscal pathology in cadaveric specimens, and 4) translation of MR techniques to a patient population with both conservative treatment and meniscectomy in the setting of meniscal tear. This is a prospective study that will use cadaveric knee specimens to carry out specific aims 1 through 3. Knee specimens will be screened with radiographs and those with severe OA as determined by radiographic grading will be excluded from the study. In specific aim 1, morphologic MR grading of menisci will be performed with standard and novel MR pulse sequences, independently by 3 subspecialized musculoskeletal radiologists. A histologic reference standard will be used to determine whether novel sequences are more sensitive to detection and classification of meniscal lesions. Our null hypothesis will be that novel MR sequences will be more accurate at unmasking normal meniscal infrastructure and structural alteration. In specific aim 2, we will compare standard quantitative MR techniques (T2 mapping, T1 rho evaluation) to novel quantitative MR techniques (UTE T2* techniques, UTE T1 rho evaluation) to determine whether novel sequences are more sensitive for the detection of altered collagen and proteoglycan respectively, in meniscal tissue. This aim will be carried out through controlled specific enzymatic digestion of cadaveric meniscal tissue. We will use analysis of bathing digestion fluid, as well as histologic and biomechanical reference standards for the digested tissue. The latter will allow us to determine whether there is the potential for quantitative MR data to reflect tissue function. Our null hypothesis will be that novel MR sequences will be more sensitive to changes in collagen and proteoglycan degradation in meniscus and cartilage. In specific aim 3, we will establish quantitative MR values for normal and pathologic menisci in cadaveric knee specimens. Further, we will identify patterns of cartilage lesions (morphologic and quantitative MR data) characteristic of each type of meniscal pathology. We will implement histologic and biomechanical reference standards. Our null hypothesis will be that quantitative MR properties will reflect the earliest structural alteration in meniscus and cartilage and that the severity of cartilage damage will correlate with type and severity of meniscal tear. In specific aim 4, we will implement novel MR imaging sequences in a patient population with meniscal tear. Patterns of meniscal tears will be characterized, and cohorts with conservative therapy and meniscectomy will be followed longitudinally. Correlation with functional clinical, and activity scores will be performed. This project has exciting implications for clinical use. The developed novel pulse sequences allow non- invasive interrogation of earliest tissue structural changes with imaging biomarkers reflecting integrity of proteoglycan and collagen in cartilage and meniscus, and calcified layer cartilage. The potential applications are limitless. While the current study focuses on OA, the leading cause of disability in the nation, second only to cardiovascular disease, these techniques could be applied to any process affecting tissue structure (degeneration, trauma, rheumatologic disease) allowing non-invasive MR evaluation of tissue infrastructure, guidance of clinical therapy, determination of progression of structural alteration, and response to therapy.