Multiparametric MRI of Cartilage

描述（由申请人提供）： 骨关节炎和类风湿性关节炎的特征在于关节软骨的进行性破坏。用于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史以及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MRI技术来评估关节软骨的成分和功能完整性，有效地建立目前使用的生物化学和组织学技术的无损替代品。基于我们在该奖项的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了三个参数，这些参数证明了最实用和分子特异性的MR测量：延迟钆增强MRI的Carbohydrate（dGEMRIC），T2和扩散，dGEMRIC已经证明了对GAG的敏感性和特异性;软骨的T2成像是基于T2对水化、胶原分子结构和通过魔角效应的胶原建筑组织的敏感性;已经显示扩散证明了胶原基质对软骨中的水的限制，并且具有证明胶原原纤维取向的潜力。在即将到来的周期中，我们建议进一步开发多参数方法，以提高对胶原蛋白组分各方面的特异性，并提高临床应用的潜力。具体目标是：（1）使用切除的牛和人软骨/骨样品进一步开发扩散成像作为胶原定向结构的度量，（2）在GdDTPA存在下实现T2和扩散成像（对于dGEMRIC研究）通过比较有和没有GdDTPA的测量，（3）通过开发三维和3 T成像解决临床dGEMRIC成像中的限制因素，（4）在早期骨关节炎和ACL损伤后两种临床情况下启动dGEMRIC和T2的临床研究。我们的总体研究目标保持不变：开发NMR/MRI技术来测量软骨的组成和功能特性。在这个周期中，我们计划继续实现我们的目标，重点关注那些最有希望获得有关软骨健康，疾病和修复的特定和敏感信息的参数，并进一步应用于临床研究。

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.