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确定关节炎的自然历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，我们使用磁共振光谱研究来证明和表征用于测量重要软骨特性的几个磁共振可测量参数的灵敏度。我们证明了水的扩散系数对软骨结构很敏感；磁化转移（MT）对胶原蛋白含量和结构敏感，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比单个测量的力量，然后我们专注于在成像模式中应用MR。鉴于磁共振成像钠的困难，我们首先专注于开发一种基于质子的磁共振方法来测量GAG浓度。所得到的技术得到了广泛的验证。高分辨率图像的空间和时间变化软骨GAG技术被广泛验证。软骨GAG的空间和时间变化的高分辨率图像突出了当组织成分的空间分布可以获得时增加的可用信息。最后，证明了该技术在人体软骨中检测GAG变异的体内（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，并将它们结合起来进行多参数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参数集的时空分布。(2)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方法来识别有或没有胶原蛋白和/或GAG异常的人体软骨区域，并在培养中监测这些样本。(4)发展并应用多参数MRI方法研究组织工程化软骨结构。因此，这些研究的长期结果将提供前所未有的机会，在离体软骨和体内临床相关分辨率下，以非破坏性的方式监测活体组织中关键软骨成分的空间分布和时间演变，这些研究以前是不可实现的。

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.