Enhanced Clinical Diagnosis of Early Osteoarthritis

描述（由申请人提供）：骨关节炎是导致残疾的主要原因，也是一个主要的公共卫生问题。关节软骨因损伤和退行性变而逐渐丧失是骨关节炎发生的重要病因。虽然实验室研究表明，在关节表面破裂之前，有可能逆转关节软骨的病理变化，但这些发现的临床转化的主要障碍是缺乏可靠的临床方法来诊断和分期关节软骨损伤和退变。这项转化临床研究将继续验证一个中心假设，即新的横断面定量成像技术可以在临床上用于改善人类关节软骨损伤和关节表面破裂前退变的诊断和分期。在最初的资助期内，我们完成了两种新型成像技术的实验室到床边的临床转化研究：光学相干断层扫描（OCT）和MRI超短回波时间（UTE）增强T2*成像，用于识别损伤和退行性关节软骨的结构变化，在视觉检查中看起来没有损伤。拟议的目标建立在初始资助期间取得的临床数据和出版物的逻辑上。这些已发表的和正在进行的纵向研究表明，我们有潜力通过R01 - 3的延续来验证临床应用的新成像技术：(1)识别仍然完好的软骨“有风险”进行性退行性变的受试者；(2)在表面破坏之前提供人体软骨表面下损伤和退行性变的体内指标。为此，我们提出以下目标。目的1将检验假设术中OCT可检测到的显微结构变化，通过术后2年和5年3.0T MRI测量的软骨厚度变化来预测进行性软骨损失。目的2将验证ute增强T2* (UTE-T2*)图谱值预测常规关节镜评估的软骨损伤和退变的假设。目的3将验证这样的假设，即术后6个月MRI定量T2松弛时间的变化可以预测术后2年MRI形态学测量确定的软骨损失。提出的目标将使用同样的两个精心选择的人群来实现，这些人群尚未患有骨关节炎，但在之前的研究中具有进行性软骨变性的高风险：(1)“骨关节炎前”退行性半月板撕裂（DMT）队列和(2)“关节损伤后”前交叉韧带撕裂（ACLT）队列。实现这些目标将提供新的定量临床诊断工具，以支持软骨损伤和退变治疗的临床范式转变，比目前可能的早几年。早期治疗的潜在优势包括延缓或预防致残性骨关节炎发病的可能性。

DESCRIPTION (provided by applicant): Osteoarthritis is a leading cause of disability, and a major public health issue. Progressive loss of articular cartilage due to injury and degeneration are important etiological factors in the development of osteoarthritis. While laboratory studies show a potential to reverse pathological changes in articular cartilage prior to breakdown of the articular surface, a major barrier to clinical translation of these findings is the lack of reliable clinical methods to diagnose and stage subsurface articular cartilage injury and degeneration. This translational clinical study will continue to test the central hypothesis that novel cross-sectional quantitative imaging technologies can be used clinically to improve diagnosis and staging of human articular cartilage injury and degeneration prior to breakdown of the articular surface. During the initial funding period, we completed bench to bedside clinical translational studies of two novel imaging technologies: Optical Coherence Tomography (OCT) and MRI ultrashort echo time (UTE) enhanced T2* mapping in identifying structural changes to injured and degenerating articular cartilage appearing undamaged to visual inspection. The proposed aims build logically on the clinical data and publications achieved during the initial funding period. These published and ongoing longitudinal studies show that we have the potential to validate, through continuation of this R01, 3 new imaging technologies for clinical use to (1) identify subjects with still intact cartilage that is "at risk" for progressive degeneration, and (2) provide in vivo metrics of subsurface injury and degeneration in human cartilage prior to surface breakdown. To achieve this, we propose the following Aims. Aim 1 will test the hypothesis intra-operative OCT detectable microstructural changes predict progressive cartilage loss as determined by changes to cartilage thickness measured on 3.0T MRI 2 and 5 years after surgery. Aim 2 will test the hypothesis that UTE-enhanced T2* (UTE-T2*) map values predict cartilage injury and degeneration as assessed by conventional arthroscopy. Aim 3 will test the hypothesis that changes in quantitative MRI T2 relaxation times six months after surgery predict cartilage loss as determined by morphometric MRI measurements 2 years after surgery. The proposed Aims will be achieved using the same two carefully selected populations of individuals who do not yet have osteoarthritis but are at high risk for progressive cartilage degeneration studied previously: (1) the "pre- osteoarthritic" degenerative meniscus tear (DMT) cohort and (2) the "post-joint injury" anterior cruciate ligament tear (ACLT) cohort. Achieving the aims will provide new quantitative clinical diagnostic tools to support a clinical paradigm shift towards treatment of cartilage injury and degeneration years before what is currently possible. Potential advantages of earlier treatment include the possibility of delaying or preventing the onset of disabling osteoarthritis.