Enhanced Clinical Diagnosis of Early Osteoarthritis

描述(申请人提供)：骨性关节炎在美国正达到流行的程度[1]。目前的临床影像方法不能在不可逆性改变开始前可靠地诊断软骨退变[2-5]。这是开发和评估新战略的主要障碍，新战略旨在通过早期干预和疾病修正治疗来延迟或预防致残性骨关节炎的发生。光学相干断层扫描(OCT)是一种新的无损光学成像技术，其在早期软骨退行性变的临床诊断中的有效性正在评估中，其父项提案《早期骨关节炎的增强临床诊断》正在进行评估。OCT能够以接近实时的微观分辨率对关节软骨成像，以检测大体正常的关节软骨内的结构变化[6-9]。PI还表明，OCT可用于临床关节镜手术，以检测软骨基质双折射的变化，预测潜在可逆的早期代谢功能不全[10]。虽然这些发现支持使用诊断成像来及早识别软骨退化的可行性，以便进行潜在的疾病改善治疗，但OCT无法通过完整的皮肤显示软骨，只能评估表层1-2毫米的关节软骨。多参数磁共振成像(MRI)还可以提供有关关节软骨结构和生化完整性的信息[11-18]。磁共振成像的优势包括非侵入性成像，以及能够成像软骨、骨和其他关节组织的全厚度。作为一种非侵入性技术，MRI可以更广泛地应用于筛查和需要对潜在的疾病修改干预措施进行定量监测和评估的纵向随访研究。然而，标准MRI(&lt；500&lt；m)的相对粗略分辨率并不接近OCT(&lt；10&lt；m)的高空间分辨率。因此，通过MRI评估软骨微结构细节仍然是难以捉摸的。我们将探索两种策略来提高MRI软骨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和(2)使用更高的磁场强度。建议与在这些领域具有创新专业知识的两名新研究人员合作，以建立一个跨学科团队，解决软组织生物学-成像技术的科学领域。成功地将早期软骨退变的OCT测量方法与MRI相关联，将显著提高母方拨款的范围和影响，以将新的成像技术转化为临床使用，以改进早期关节软骨退变的诊断和分期。

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.