Infrared fiber optic imaging of degenerative cartilage

描述(申请人提供)：骨性关节炎是一种高度流行的、渐进性致残的肌肉骨骼疾病，其特征是关节软骨退化。开发这种疾病治疗方法的一个重要障碍是难以评估旨在诱导软骨修复组织产生的治疗干预措施。我们建议使用傅里叶变换红外(FTIR)光谱分析来实现这个目标。到目前为止，我们的实验室已经证明，使用中红外光纤探头(MID-IFOP)从软骨表面获得的光谱与发生在宏观损伤之前的早期软骨退化的组织学迹象之间存在显著的相关性。我们建议在此基础上，将我们的方法扩展到软骨修复的环境中，我们设想使用IFOP中期作为关节镜诊断工具来评估修复组织。这将通过优化光谱采集和应用化学计量学方法(基于统计学的模式识别方法，用于根据光谱特征对材料进行识别或分类)来实现，以将光谱数据与组织的分子特征相关联。这将提供临床上有用的数据，用于评估软骨修复，同时增加关节镜手术的最短时间。我们的方法将首先在对兔修复过程的纵向研究中发展起来，然后应用于从患者的活检中获得的修复组织的分类。在后一项分析中的一个关键点将是建立红外光谱衍生的修复组织分类与临床结果之间的相关性。这些数据将为随后在体内研究正在进行的人类软骨修复奠定基础。总之，我们注意到，目前还没有非破坏性的方法来检测和分类软骨修复组织中的细微分子变化，并将这种变化与组织学分级和临床结果联系起来；因此，我们提出的分析可能代表着新兴的骨关节炎治疗领域的重要进展。 关节软骨的自我修复能力有限，软骨缺陷通常在没有干预的情况下进展为广泛的退化。中红外光纤探头应用的开发可以提供原位监测软骨修复组织分子特征的能力，从而允许在持续的基础上进行适当的干预。因此，通过提供这种能力，这项技术的发展可能会在极其重要的组织再生领域发挥真正的核心作用。

DESCRIPTION (provided by applicant): Osteoarthritis is a highly prevalent, progressively disabling musculoskeletal disease characterized by degeneration of articular cartilage. A significant barrier to the development of therapy for this disorder is the difficulty in assessing therapeutic interventions designed to induce the production of cartilage repair tissue. We propose the use of Fourier transform infrared (FTIR) spectroscopic analysis towards this goal. To date, our laboratory has demonstrated a significant correlation between spectra obtained from the cartilage surface using a mid-infrared fiber optic probe (mid-IFOP), and histological signs of early cartilage degradation which occur prior to macroscopic damage. We propose to build on this by extending our methodology to the setting of cartilage repair, where we envision use of the mid-IFOP as an arthroscopic diagnostic tool to evaluate repair tissue. This will be accomplished by optimization of spectral acquisition and application of chemometric methods (statistically based pattern-recognition methods used to identify or classify materials based on their spectral characteristics) to correlate spectral data with molecular characteristics of the tissue. This will provide data which is clinically useful in assessing cartilage repair while adding minimal time to arthroscopic procedures. Our methodology will first be developed in a longitudinal study of the repair process in the rabbit, and then applied to classification of repair tissue obtained by biopsy from patients. A key point in the latter analysis will be to establish the correlation between infrared spectroscopy-derived repair tissue classification and clinical outcomes. These data will lay the foundation for subsequent in vivo investigation of ongoing cartilage repair in humans. In summary, we note that there are currently no non-destructive methods available for detection and classification of subtle molecular changes in cartilage repair tissue, and for relating such changes to histologic grade and clinical outcome; therefore, the analyses we propose may represent an important advance in the emergent field of OA therapeutics. PUBLIC HEALTH RELEVANCE Articular cartilage exhibits limited capacity for self-repair, and chondral defects typically progress to widespread degradation without intervention. The development of the mid infrared fiber optic probe application could offer the ability to monitor cartilage repair tissue molecular characteristics in situ, and thus permit appropriate interventions to be undertaken on an ongoing basis. Therefore, the development of this technique may play a truly central role in the exceedingly important field of tissue regeneration by offering this capability.