MULTIPARAMETRIC MRI OF CARTILAGE

准确评估软骨结构和功能完整性的非破坏性技术对于定义关节炎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磁共振成像（MRI）技术来评估关节软骨的组成和功能完整性。在该奖项的第一个周期中，我们使用MR光谱研究来证明和表征几个MR可测量参数的灵敏度，这些参数旨在测量重要的软骨特性。我们证明水的扩散系数对软骨结构敏感;磁化传递（MT）对胶原含量和结构敏感，钠浓度可用于定量GAG浓度。此外，白细胞介素-1和胰蛋白酶降解的比较研究揭示了多参数方法对个体测量的影响。然后，我们专注于在成像模式中应用MR。鉴于通过MR对钠进行成像的困难，我们首先专注于开发用于测量GAG浓度的基于质子的MR方法。由此产生的技术得到了广泛的验证。软骨GAG技术的空间和时间变化的高分辨率图像被广泛验证。软骨GAG的空间和时间变化的高分辨率图像突出了当可以获得组织成分的空间分布时可用的增加的信息。最后，证明了该技术检测人软骨中GAG变化的体内（临床）可行性和有效性。下一个周期的总体目标是探索成像模式下的其他MR参数，并将其联合收割机用于多参数MRI研究。本研究的具体目的是：（1）比较培养牛软骨诱导降解和再生过程中MRI参数的时空分布。(2)目的：将多参数MRI方法应用于自然疾病不同阶段的人体组织。(3)使用已开发的MR测量方法识别存在和不存在已识别胶原和/或GAG异常的人软骨区域，并监测培养物中的这些样本。(4)建立组织工程化软骨的多参数MRI成像技术。因此，这些研究的长期结果将产生前所未有的机会，以非破坏性地监测活组织中关键软骨成分的空间分布和时间演变，在分离的软骨中以接近组织学的分辨率和在临床相关的分辨率在体内，这些研究以前是不可行的。

Non-destructive techniques for accurately assessing the structural and functional integrity of cartilage are essential for defining the natural history of arthritis and for evaluating the effects of prevention and therapeutic interventions. Our long term goal is to establish magnetic resonance imaging (MRI) techniques for evaluating the compositi0nal and functional integrity of articular cartilage. In the first cycle of this award, we used MR spectroscopy studies to demonstrate and characterize the sensitivity of several MR measurable parameters designed to measure important cartilage properties. We demonstrated that diffusivity of water was sensitive to cartilage structure; magnetization transfer (MT) was sensitive to collagen content and structure, and sodium concentrat6ion could be used to quantify GAG concentration. Furthermore, comparative studies of interleukin-1 and trypsin degradation revealed the power of a multiparametric approach over individual measurements We then focused on applying MR in an imaging mode. Given the difficulties in imaging sodium by MR, we first focused on developing a proton based MR method for measuring GAG concentration. The resulting technique was extensively validated. High resolution images of spatial and temporal variations in cartilage GAG technique was extensively validated. High resolution images of spatial and temporal variations in cartilage GAG highlighted the increased information available when the spatial distribution of tissue constituents can be obtained. Finally, the in vivo (clinical) feasibility and validity of this technique to detect variations in GAG in human cartilage was demonstrated. The overall aim of this next cycle is to explore the other MR parameters in an imaging mode and combine them for a multiparametric MRI study. The specific aims of this proposal are: (1) To compare the spatial and temporal distribution of the set of MRI parameters during induced degradation and regeneration of bovine cartilage in culture. (2) To apply the multi multiparametric MRI approach to human tissue in different stages of natural disease. (3) To use the developed MR measures to identify areas of human cartilage with and without identified collagen and/or GAG abnormalities, and monitor these samples in culture. (4) To develop and apply the multiparametric MRI approach to tissue engineered cartilage constructs. The long term results of these studies should therefore yield the unprecedented opportunity to non-destructively monitor the spatial distribution and temporal evolution of critical cartilage constituents in living tissue at near-histologic resolution in isolated cartilage and at clinically relevant resolutions in vivo, studies which were previously not feasible.