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，也是一个重大的公共卫生问题。关节软骨损伤和退变导致的进行性软骨丢失是骨关节炎发生发展的重要病因。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，但这些发现临床转化的一个主要障碍是缺乏可靠的临床方法来诊断和分期关节表下软骨损伤和退变。这项转化性临床研究将继续检验这一中心假设，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退变在关节表面破裂之前的诊断和分期。在最初的资助期间，我们完成了两项新成像技术的工作台到床边的临床翻译研究：光学相干断层扫描(OCT)和磁共振超短回波时间(UTE)增强T2*映射，用于识别目测未受损的受损和退变的关节软骨的结构变化。拟议的目标建立在最初筹资期间取得的临床数据和出版物的基础上。这些已发表的和正在进行的纵向研究表明，通过R01的延续，我们有可能验证3种临床使用的新成像技术，以(1)识别软骨仍完好的受试者，并“面临”进行性退化的风险，以及(2)提供人体软骨在表面破裂之前的表面下损伤和退化的活体测量指标。为了实现这一目标，我们提出了以下目标。目的1验证手术中OCT可检测到的微结构变化预测进行性软骨丢失的假说，根据术后2年和5年3.0TMRI测量的软骨厚度变化来确定。目的2将验证UTE增强T2*(UTE-T2*)MAP值预测软骨损伤和退变的假说，正如传统关节镜评估的那样。目的3将验证这样的假设，即术后6个月定量MRI T2松弛时间的变化预测术后2年形态测量MRI测量所确定的软骨丢失。建议的目标将使用之前研究过的两组精心挑选的尚未患上骨关节炎但具有进行性软骨退行性变高风险的人群来实现：(1)“骨关节炎前期”退行性半月板撕裂(DMT)队列和(2)“关节损伤后”前十字韧带撕裂(ACLT)队列。实现这些目标将提供新的量化临床诊断工具，以支持临床范式的转变，比目前可能的治疗软骨损伤和退变早几年。早期治疗的潜在优势包括有可能延迟或预防致残性骨关节炎的发生。

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.