Ultrashort TE MR Imaging of Femorotibial Cartilage

股胫软骨超短 TE MR 成像

• 批准号: 8413387
• 负责人: CHRISTINE B CHUNG
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8413387
• 关键词: Affect; Anatomy; Bathing; Binding; Biochemical; Biological Assay; Biological Markers; Biological Models; Biomechanics; Calcified; Cardiovascular Diseases; Cartilage; Characteristics; Classification; Clinical; Collagen; Data; Degenerative polyarthritis; Detection; Development; Diagnosis; Digestion; Disease; Enrollment; Evaluation; Glycosaminoglycans; Histologic; Histopathology; Hydroxyproline; Image; Joints; Knee; Lesion; Liquid substance; Magnetic Resonance Imaging; Maps; Measures; Mechanics; Meniscus structure of joint; Monitor; Musculoskeletal; Normal Range; Operative Surgical Procedures; Osteoarthrosis Deformans; Pathogenesis; Pathologic; Pathology; Patients; Pattern; Physiologic pulse; Polarization Microscopy; Preparation; Process; Property; Prospective Studies; Proteoglycan; Radial; Reference Standards; Research Infrastructure; Sampling; Severities; Specimen; Staining method; Stains; Structure; Techniques; Testing; Tissues; Translations; Trauma; Treatment Efficacy; Trypsin; Validation; Water; Work; articular cartilage; base; cohort; collagenase; disability; in vitro Model; novel; patient population; radiologist; response; rho

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.

描述（由申请人提供）： 该研究的总体目的是开发和研究具有组织学和生物力学参考标准的新型 MR 成像生物标志物，以检测软骨和半月板的结构变化，并应用这些技术来表征退变模式，从而有助于了解膝关节 OA 的发病机制。提出了四个具体目标（SA）：1）利用组织学参考标准验证用于定性半月板表征的新型 MR 脉冲序列，2）利用组织学和生物力学参考标准验证检测半月板胶原和蛋白多糖变化的新型 MR 脉冲序列，3）探索尸体标本中软骨病变和半月板病理学的关系，以及 4）MR 技术的转化 半月板撕裂时接受保守治疗和半月板切除术的患者群体。这是一项前瞻性研究，将使用尸体膝关节标本来实现具体目标 1 至 3。膝关节标本将通过 X 光照片进行筛选，根据 X 光分级确定患有严重 OA 的患者将被排除在研究之外。在具体目标 1 中，半月板的形态学 MR 分级将由 3 名亚专业肌肉骨骼放射科医生独立使用标准和新颖的 MR 脉冲序列进行。将使用组织学参考标准来确定新序列是否对半月板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半月板基础设施和结构改变。在具体目标 2 中，我们将比较标准定量 MR 技术（T2 映射、T1 rho 评估）与新型定量 MR 技术（UTE T​​2* 技术、UTE T​​1 rho 评估），以确定新序列是否对于分别检测半月板组织中改变的胶原蛋白和蛋白多糖更敏感。这一目标将通过对尸体半月板组织进行受控的特定酶消化来实现。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，新的 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加敏感。在具体目标 3 中，我们将建立尸体膝关节标本中正常和病理半月板的定量 MR 值。此外，我们将确定每种半月板病理类型的软骨损伤模式（形态学和定量 MR 数据）特征。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变化，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，我们将在半月板撕裂患者群体中实施新颖的 MR 成像序列。将描述半月板撕裂的模式，并对保守治疗和半月板切除术的队列进行纵向随访。将进行与功能性临床和活动评分的关联。该项目对临床应用具有令人兴奋的影响。开发的新型脉冲序列允许利用反映软骨和半月板以及钙化层软骨中蛋白多糖和胶原蛋白完整性的成像生物标志物对最早的组织结构变化进行非侵入性询问。潜在的应用是无限的。虽然目前的研究重点是骨关节炎（OA），这是全国残疾的主要原因，仅次于心血管疾病，但这些技术可应用于影响组织结构的任何过程（变性、创伤、风湿病），从而允许对组织基础设施进行非侵入性 MR 评估、指导临床治疗、确定结构改变的进展以及对治疗的反应。