Multiparametric MRI of Cartilage

描述(由申请人提供)： 骨性关节炎和类风湿性关节炎的特征是关节软骨的进行性破坏。准确评估软骨结构和功能完整性的非破坏性技术，如磁共振成像(MRI)，对于确定这些关节疾病的自然历史和评估预防和治疗干预的效果至关重要。我们的长期目标是建立用于评估关节软骨成分和功能完整性的MRI技术，有效地建立非破坏性替代目前使用的生化和组织学技术。基于我们在该奖项前两个周期的进展以及其他小组的工作，我们最近将重点转向三个参数，它们展示了最实用和最具分子特异性的MR测量：延迟Gd增强软骨磁共振成像(DGEMRIC)，T2，以及扩散，dGEMRIC显示了对GAG的敏感性和特异性；T2软骨成像基于T2对水化的敏感性，胶原分子结构，以及通过魔角效应的胶原结构；扩散已被证明胶原基质对软骨中的水分的限制，并有可能显示胶原原纤维的取向。在接下来的周期中，我们建议进一步开发多参数方法，以提高胶原成分的某些方面的特异性，以及提高临床应用的潜力。具体目标是：(1)利用切除的牛和人软骨/骨样本，进一步开发扩散成像作为胶原定向结构的度量；(2)通过比较使用和不使用GdDTPA的测量结果，实现T2和在GdDTPA存在的情况下的扩散成像(用于dGEMRIC研究)；(3)通过开发三维和3T成像，解决临床dGEMRIC成像的限制因素；以及(4)启动dGEMRIC和T2的临床研究，用于早期骨关节炎和前交叉韧带损伤后的两种临床情况。我们的总体研究目标保持不变：开发核磁共振/核磁共振技术来测量软骨的成分和功能特性。在这个周期中，我们计划继续朝着我们的目标前进，专注于显示关于软骨健康、疾病和修复的特定和敏感信息的最有希望的参数，并进一步将其应用于临床研究。

DESCRIPTION (provided by applicant): Osteoarthritis and rheumatoid arthritis are characterized by progressive destruction of articular cartilage. Nondestructive techniques for accurately assessing the structural and functional integrity of cartilage, such as magnetic resonance imaging (MRI), are essential for defining the natural history of these joint diseases and for evaluating the effects of preventive and therapeutic interventions. Our long-term goal is to establish MRI techniques for evaluating the compositional and functional integrity of articular cartilage, effectively establishing nondestructive surrogates to currently utilized biochemical and histologic techniques. Based on our progress during the first two cycles of this award and on work by other groups, we have recently turned our focus to three parameters which have demonstrated the most practical and molecular-specific MR measurements: delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC), T2, and diffusion, dGEMRIC has demonstrated sensitivity and specificity to GAG; T2 imaging of cartilage is based on the sensitivity of T2 to hydration, collagen molecular structure, and collagen architectural organization through the magic angle effect; diffusion has been shown to demonstrate the restriction of water in cartilage by the collagen matrix, and has the potential to demonstrate the collagen fibril orientation. In this coming cycle, we propose to further develop the multiparametric approach to yield improved specificity for aspects of the collagen component, as well as improving the potential of clinical applications. The specific aims are: (1) Further develop diffusion imaging as a metric of collagen orientational structure using excised bovine and human cartilage/bone samples, (2) enable T2 and diffusion imaging in the presence of GdDTPA (for dGEMRIC studies) by comparing the measurements with and without GdDTPA, (3) address the limiting factors in clinical dGEMRIC imaging by developing three dimensional and 3T imaging, and (4) initiate clinical studies of dGEMRIC and T2 in two clinical situations of early osteoarthritis and patients post ACL injury. Our overall research goal has remained the same: developing NMR/MRI techniques to measure the compositional and functional properties of cartilage. In this cycle we plan to continue towards our goal by focusing in on the parameters that show the most promise for specific and sensitive information regarding cartilage health, disease, and repair, and furthering the application to clinical studies.