Enhanced Clinical Diagnosis of Early Osteoarthritis

描述（由申请人提供）：骨关节炎在美国已达到流行病的程度。目前的临床成像方式无法在不可逆变化发生之前可靠地诊断软骨退变[2-5]。这是开发和评估通过早期干预疾病修饰治疗延迟或预防致残性骨关节炎发病的新策略的主要障碍。光学相干断层扫描（OCT）是一种新型的无损光学成像技术，在早期软骨退变的临床诊断中的有效性在母提案“增强早期骨关节炎的临床诊断”中得到了评估。OCT能够以近乎实时的显微分辨率对关节软骨进行成像，以检测大体正常的关节软骨的结构变化[6-9]。PI还表明，OCT可以在关节镜手术中用于临床检测软骨基质双折射变化，预测潜在可逆的早期代谢不全[10]。虽然这些发现支持了使用诊断成像早期识别软骨退行性变的可行性，以便进行潜在的疾病改善治疗，但OCT不能通过完整的皮肤观察软骨，并且只能评估关节软骨表面的1-2毫米。多参数磁共振成像（MRI）也可以提供关节软骨结构和生化完整性的信息[11-18]。MRI的优点包括无创成像和对软骨、骨和其他关节组织的全厚度成像的能力。作为一种无创技术，MRI可以更广泛地应用于筛查和需要定量监测和评估潜在疾病改善干预措施的纵向随访研究。然而，标准MRI的相对粗分辨率（<500 <m）无法达到OCT的高空间分辨率（<10 <m）。因此，通过MRI评估软骨微观结构细节仍然难以捉摸。我们将探索两种策略来提高MRI软骨评估的对比度和空间分辨率，使其更接近OCT:(1)使用新的软骨成像序列，(2)使用更高的磁场强度。建议与两名在这些领域具有创新专业知识的新研究人员合作，建立一个跨学科团队，解决软组织生物成像技术的科学领域。早期软骨退行性变的OCT测量与MRI的成功关联，将显著增加父母资助的范围和影响，将新的成像技术转化为临床应用，以改善早期关节软骨退行性变的诊断和分期。

DESCRIPTION (provided by applicant): Osteoarthritis is reaching epidemic proportions in the United States [1]. Current clinical imaging modalities are unable to reliably diagnose cartilage degeneration prior to the onset of irreversible changes [2-5]. This is a major obstacle to the development and assessment of new strategies to delay or prevent the onset of disabling osteoarthritis through early intervention disease modifying treatments. The effectiveness of optical coherence tomography (OCT), a novel nondestructive optical imaging technology, for clinical diagnosis of early cartilage degeneration is under evaluation in the parent proposal, "Enhanced Clinical Diagnosis of Early Osteoarthritis". OCT is capable of imaging articular cartilage at microscopic resolutions in near real time to detect structural changes within grossly normal appearing articular cartilage [6-9]. The PI has also shown that OCT can be used clinically during arthroscopic surgery to detect changes to cartilage matrix birefringence predictive of potentially reversible early metabolic incompetence [10]. While these findings support the feasibility of using diagnostic imaging to identify cartilage degeneration early enough for potential disease modifying treatment, OCT cannot visualize cartilage through intact skin and evaluates only the superficial 1-2 millimeters of articular cartilage. Multi-parametric magnetic resonance imaging (MRI) can also provide information about articular cartilage structure and biochemical integrity [11-18]. Advantages of MRI include noninvasive imaging and the ability to image the full thickness of the cartilage as well as bone and other joint tissues. As a noninvasive technology, MRI can be more broadly applied for screening and for longitudinal follow-up studies requiring quantitative monitoring and evaluation of potential disease modifying interventions. However, the relatively gross resolutions of standard MRI (<500 <m) do not approach the high spatial resolution of OCT (<10 <m). As such, evaluation of cartilage microstructural detail through MRI remains elusive. We will explore two strategies for improving the contrast and spatial resolution of MRI cartilage evaluation closer to that of OCT: (1) the use of novel cartilage imaging sequences and (2) the use of higher magnet field strengths. Collaborations with two new investigators who have innovative expertise in these areas are proposed to build an interdisciplinary team addressing the scientific areas of Soft Tissue Biology-Imaging Technologies. Successful correlation of OCT measures of early cartilage degeneration with MRI would significantly enhance the scope and impact of the parent grant towards translation of new imaging technologies into clinical use for improved diagnosis and staging of early articular cartilage degeneration.