Quantitative molecular imaging in articular cartilage

描述（由申请人提供）：由于缺乏检测软骨降解的非侵入性和分子特异性生物标志物，因此无法从根本上了解骨关节炎（OA）的发展以及OA的早期诊断和干预。与监测图像强度或面积/体积的常规磁共振成像（MRI）不同，显微MRI（uMRI）非常适合关节软骨的定量研究。MRI不仅可以生成水分布的2D和3D图像，还可以生成以显微分辨率反映组织中分子环境的独特参数的图像。在我们目前的软骨研究中，我们使用了组织学金标准，偏振光显微镜（PLM），以验证14微米分辨率的uMRI结果。我们证明，通过T2各向异性的魔角成像uMRI可以检查在软骨中的各个组织学区域的超微结构特性，具有高灵敏度和分子特异性。该提案有五个具体目标。目的1-3研究各向异性！软骨中三种主要分子组分（胶原纤维、蛋白聚糖、水）在显微镜分辨率下的分布/相互作用。目的4将组织块的显微镜研究扩展到中等分辨率下完整关节的研究。目的5使用全身MRI扫描仪将成像研究进一步扩展到临床应用中。结合起来，这五个目标将产生其他不可用的新信息，以非破坏性地阐明这种重要生物材料的各种生物物理，生物化学和生物学机制和特性。我们的建议是独特的结合定量和显微成像技术（uMRI，PLM，电子显微镜，傅立叶变换红外成像），空间分辨分子特异性标记物，和组织学的细节。由于骨关节炎和组织中的大分子所表现出的相互依赖的结构-功能关系的复杂的分子变化，我们的多学科的方法可以区分各种可能的生化和超微结构状态及其对组织的功能完整性的影响。我们的目标是（1）定量表征健康和病变组织的特性，以及（2）确定一组基线！指南T2各向异性成像的成功临床应用，从而提供关键信息的理解，并最终预防关节炎疾病。

DESCRIPTION (provided by applicant): A lack of non-invasive and molecular-specific biomarkers to detect cartilage degradation has prevented a fundamental understanding of the development of osteoarthritis (OA), as well as early diagnosis of and intervention in OA. Unlike conventional Magnetic Resonance Imaging (MRI) that monitors image intensity or area/volume, Microscopic MRI (uMRI) is well-suited for the quantitative study of articular cartilage. MRI can produce 2D and 3D images not only of water distribution, but also of unique parameters reflecting the molecular environment in the tissue at microscopic resolution. In our current studies of cartilage, we have used the histology gold-standard, polarized light microscopy (PLM), to validate the 14um-resolution uMRI results. We demonstrate that the magic-angle imaging via T2- anisotropy in uMRI can examine the ultrastructural properties in individual histological zones in cartilage with high sensitivity and molecular specificity. This proposal has five Specific Aims. Aims 1-3 study the anisotropy ! distribution / interactions of three major molecular components in cartilage (collagen fibrils, proteoglycans, water) at microscopic resolution. Aim 4 extends the microscopic study of tissue blocks to the study of intact whole joint at intermediate resolution. Aim 5 extends the imaging study further into the clinical application using a whole-body MRI scanner. In combination, these five aims will yield otherwise unavailable new information to elucidate nondestructively various biophysical, biochemical and biological mechanisms and properties in this important biomaterial. Our proposal is unique in combining quantitative and microscopic imaging techniques (uMRI, PLM, electron microscopy, Fourier-transform infrared imaging), spatially-resolved molecular-specific markers, and histological details. In view of complicated molecular changes due to osteoarthritis and the interdependent structure-function relationships exhibited by macromolecules in tissue, our multi-disciplinary approach can discriminate among the various possible biochemical and ultrastructural states and their influence on the functional integrity of the tissue. We aim (1) to characterize the properties of both healthy and lesioned tissues quantitatively, and (2) to determine a set of baselines ! guidelines for the successful clinical application of T2 anisotropy imaging, thus providing critical information towards the understanding, and ultimately, prevention of arthritic diseases.