Physiology of Inflammatory Arthritis in High Resolution

描述(由申请人提供)：开发和应用新的成像技术，以发现炎症性关节炎疾病发生、发展和治疗反应的生物标记物，引起了广泛的兴趣，也是医生、医学研究人员和NIH等科学实体的共同目标。创新的光谱光声断层成像(SPAT)在软组织中呈现高分辨率光学信息，成像深度可达几厘米，在诊断和治疗炎症性关节炎方面具有重大优势，特别是与更成熟的超声成像(US)相结合。SPAT除了捕获外周骨骼和软组织图像外，还具有量化组织血液动力学特性的独特能力，包括局部血氧和血容量，这两项在与炎症性关节炎相关的滑膜组织中都是异常的。因此，SPAT的发现将导致新的直接和敏感的组织特异性生物标记物的创建，并可能对关节炎的临床治疗产生革命性的影响。基于我们过去在动物和人类身体关节上的验证，在拟议的研究中，这种生理成像模式将首次适用于人类炎症性关节炎。通过与NIH超声换能器资源中心的合作，我们将利用最先进的超声成像和换能器开发技术开发专门设计的SPAT和美国双模系统。该系统将能够同时对人体周围关节进行SPAT和US实时成像。此外，它还可以为医生提供光学和超声对比以及组织生理信息。通过在正常志愿者和类风湿关节炎患者身上的实验，我们将检验SPAT和US在周围关节关节组织结构成像中的表现，以及它们显示类风湿关节炎形态生物标志物的能力。更有趣的是，我们将探索SPAT在评估包括充血和缺氧在内的滑膜炎新的生理生物标志物方面的潜力。我们预计，这种不使用造影剂但灵敏度和特异度与核磁共振相当的成像技术，可能会为关节炎提供独特的机会，包括预先诊断、识别最初的自然疾病后遗症和进展，以及监测非药物和基于药物的干预措施。

DESCRIPTION (provided by applicant): Development and application of new imaging technologies for the discovery of biomarkers of inflammatory arthritic disease onset, progression, and response to therapy are of broad interest and are common goals of physicians, medical researchers and scientific entities such as the NIH. Presenting high resolution optical information in soft tissues with imaging depth up to several centimeters, innovative spectroscopic photoacoustic tomography (SPAT) offers significant benefits to the diagnosis and treatment of inflammatory arthritis, particularly in combination with more established ultrasound imaging (US). SPAT, in addition to capturing peripheral bone and soft tissue images, has the unique capability to quantify tissue hemodynamic properties including regional blood oxygenation and blood volume, both abnormal in synovial tissue associated with inflammatory arthritis. Therefore, findings from SPAT should lead to creation of new direct and sensitive tissue-specific biomarkers, and may have revolutionary impact on clinical management of arthritis. Based on our past validation in animals and human cadaver joints, this physiological imaging modality will be adapted to human inflammatory arthritis for the first time in the proposed research. Through collaboration with the NIH Ultrasonic Transducer Resource Center, we will develop a specially designed SPAT and US dual-modality system employing the state-of-the-art ultrasonic imaging and transducer development technologies. This system will enable simultaneous SPAT and US imaging of human peripheral joints in real-time. Moreover, it can present physicians with both optical and ultrasonic contrast as well as tissue physiological information. Through the experiments on normal volunteers and rheumatoid arthritis patients, we will examine the performance of SPAT and US in imaging the articular tissue structures of peripheral joints and their ability in visualizing morphological biomarkers of rheumatoid arthritis. More interestingly, we will explore the potential of SPAT in assessing new physiological biomarkers of synovitis including hyperemia and hypoxia. We expect that, with sensitivity and specificity comparable to MRI but without using a contrast agent, this cost-effective imaging may provide unique opportunities for arthritis, including pre-diagnosis, identification of initial natural disease sequelae and progression, along with monitoring of non-pharmaceutical and pharmaceutical based interventions.