Quantitative molecular imaging in articular cartilage

描述（由申请人提供）：缺乏检测软骨退化的非侵入性和分子特异性生物标志物，阻碍了对骨关节炎（OA）发展的基本理解，以及OA的早期诊断和干预。与监测图像强度或面积/体积的传统磁共振成像（MRI）不同，显微MRI （uMRI）非常适合关节软骨的定量研究。MRI不仅可以产生水分布的二维和三维图像，还可以在微观分辨率下产生反映组织中分子环境的独特参数。在我们目前对软骨的研究中，我们使用了组织学的金标准，偏振光显微镜（PLM），来验证14um分辨率的uMRI结果。我们证明了uMRI中通过T2-各向异性的魔角成像可以以高灵敏度和分子特异性检测软骨单个组织学区域的超微结构特性。这项建议有五个具体目标。目的1-3研究各向异性！软骨中三种主要分子成分（胶原原纤维、蛋白聚糖、水）在显微分辨率下的分布/相互作用Aim 4将组织块的显微研究扩展到中分辨率完整全关节的研究。目的5将成像研究进一步扩展到使用全身MRI扫描仪的临床应用。结合这五个目标，将产生其他无法获得的新信息，以非破坏性地阐明这种重要生物材料的各种生物物理，生化和生物学机制和特性。我们的建议在结合定量和显微成像技术（uMRI， PLM，电子显微镜，傅里叶变换红外成像），空间分辨分子特异性标记和组织学细节方面是独一无二的。鉴于骨关节炎引起的复杂分子变化以及组织中大分子所表现出的相互依赖的结构-功能关系，我们的多学科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功能完整性的影响。我们的目标是(1)定量地描述健康和病变组织的特性，(2)确定一组基线！为T2各向异性成像的成功临床应用提供指南，从而为理解并最终预防关节炎疾病提供关键信息。

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.