MRI Biomarkers in Assessing Articular Cartilage Health

评估关节软骨健康的 MRI 生物标志物

• 批准号: 7347196
• 负责人: Douglas Ray Pedersen
• 金额: $ 23.44万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7347196
• 关键词: Acute; Benchmarking; Biochemical; Biochemistry; Biological Markers; Biomechanics; Biometry; Cartilage; Cartilage injury; Chondrocytes; Clinic; Clinical; Collagen; Competence; Condition; Contrast Media; Contusions; Cytoskeleton; Defect; Diagnostic; Elements; Environment; Evaluation; Event; Extracellular Matrix; Fluorescence; Gadolinium; Gold; Harvest; Health; Image; Imagery; Injury; Joints; Knee; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mechanics; Methods; Metric; Modeling; Monitor; Morphology; Operative Surgical Procedures; Outcome; Outcome Measure; Patients; Physiologic pulse; Physiological; Positioning Attribute; Preparation; Process; Property; Prospective Studies; Proteoglycan; Protocols documentation; Pulse taking; Randomized; Rehabilitation therapy; Relaxation; Research; Research Personnel; Series; Signal Transduction; Site; Specimen; Standards of Weights and Measures; Synovial Fluid; Techniques; Testing; Time; Tissues; Translations; Treatment Effectiveness; Water; articular cartilage; base; bone; day; improved; in vivo; indexing; injured; programs; reconstruction; treatment planning; uptake

Magnetic resonance imaging (MRI) maintains its position as the gold standard for visualization of cartilage defects and overall assessment of cartilage morphology. However, the earliest markers of cartilage degeneration occur at the tissue level and are therefore not detectable as changes in morphology. At present, there exists no effective way to objectively assess this element of cartilage health noninvasively. The lack of quantitative measures of cartilage condition hampers treatment planning and meaningful assessment of joint injuries. Numerous MR-based methods have been proposed to noninvasively display and quantitate changes in the composition and integrity of such elements of cartilage extracellular matrix (ECM) as proteoglycan (PG) and collagen content in vivo. Among techniques that have been applied in clinical subjects, T2 MRI is sensitive to several processes involved in cartilage degeneration. Delayed Gadolinium-enhanced MRI of cartilage (dGEMRIC) provides an index that is most directly correlated to PG content, but relies on the selective uptake of intravenously administered contrast agent. T1rho MRI utilizes magnetization preparation pulses without contrast administration, to yield parametric maps that also correlate strongly with PG content. Clinical interpretation of MRI biochemical metrics is still unproven, either by clinical or by benchtop MRI-biochemistry studies. No studies have directly compared MRI measurements in the clinic (in vivo) with MRI-biochemistry-biomechanics measurements on that same tissue in the research environment (ex vivo), to build a bridge for direct translation of research results to clinical interpretation. The research here proposed will test the hypothesis that noninvasive PG-sensitive MRI in combination with water/collagen-sensitive MRI provides an early diagnostic measure of cartilage condition after acute injury and at 2 years post-injury, as an objective evaluation of joint and articular health. We propose SA1) to directly quantify the concordance between PG-sensitive in vivo clinical MRI and ex vivo MRI biochemical metrics with histochemical, biochemical, and biomechanical measurements within articular cartilage sections; SA2) to demonstrate a combination of T1rho/T2 relaxation sequence metrics as a biomarkerto assess cartilage health and mechanical function, SA3); to apply T1rho/T2 MRI clinically at time of injury as a benchmark for acute post-injury treatment effectiveness, and as a rehabilitation and outcomes measure.

磁共振成像（MRI）保持其地位作为黄金标准可视化软骨 缺损和软骨形态的总体评估。然而，最早的软骨标记 变性发生在组织水平，因此不能检测到形态学的变化。在 目前还没有有效的方法来客观地非侵入性地评估软骨健康的这种因素。 缺乏软骨状况的定量测量阻碍了治疗计划和有意义的治疗。 评估关节损伤。已经提出了许多基于MR的方法来非侵入性地显示 并定量软骨细胞外基质的这些成分的组成和完整性的变化 (ECM)以体内蛋白多糖（PG）和胶原含量为指标。在已经应用于 在临床受试者中，T2 MRI对涉及软骨退变的几个过程敏感。延迟 软骨钆增强MRI（dGEMRIC）提供了与PG最直接相关的指标 内容物，但依赖于静脉内施用的造影剂的选择性摄取。T1 rho MRI利用 无需给予对比剂的磁化准备脉冲，以产生参数图，该参数图还 与PG含量密切相关。MRI生化指标的临床解释也尚未得到证实 通过临床或台式MRI-生物化学研究。没有研究直接比较MRI测量结果 在临床（体内）中，对研究中的相同组织进行MRI-生物化学-生物力学测量 环境（离体），以建立一个桥梁，直接翻译的研究结果，以临床解释。的 本文提出的研究将检验一种假设，即非侵入性PG敏感MRI结合 水/胶原敏感MRI提供了急性损伤后软骨状况的早期诊断措施 在损伤后2年，作为关节和关节健康的客观评价。我们建议SA 1）， 直接量化PG敏感的体内临床MRI和离体MRI生物化学之间的一致性 关节软骨内组织化学、生物化学和生物力学测量指标 部分; SA 2），以证明T1 rho/T2弛豫序列度量的组合作为生物标志物， 评估软骨健康和机械功能，SA 3）;在损伤时临床应用T1 rho/T2 MRI， 急性损伤后治疗有效性的基准，并作为康复和结果的衡量标准。