Imaging of Inflammation and Treatment: Basic and Translational Potential

说明（申请人提供）：随着医学成像技术的发展，不仅可以监测分析探针或治疗剂的递送，而且可以全面客观地评价治疗效果，将大大改善细胞和分子水平上的疾病治疗和诊断。作为一种新兴的非侵入性、非电离光成像技术，光声层析成像（photoacoustic tomography，PAT）具有高对比度和高空间分辨率的特点，有望成为一种新型的、有前途的分子成像技术，在医学领域发挥重要作用。我们建议研究一种更先进的光谱PAT（SPAT）技术，使用炎症性关节炎疾病模型，模式后广为人知的，非常昂贵的，痛苦的，和禁用的疾病，演示的方法。SPAT在新开发的金纳米胶体造影剂的帮助下，可能会在各种生物医学应用中产生广泛影响的创新，不仅在活体实验动物中更有效地评估药物作用，而且在临床实践中优化治疗决策。用于人类/动物炎症性关节炎的SPAT系统将在一个独立的商业超声单元上开发，该单元在独家研究模式下允许同时采集64个独立通道的光诱导超声信号。该功能将首次实现近实时2D PAT和快速3D PAT。具有调谐到近红外区域的光学吸收峰的金纳米棒将与FDA批准的治疗类风湿性关节炎的药物依那西普（Enbrel（r））结合。由于金纳米棒的强光吸收，SPAT系统与设计的PVDF阵列换能器一起工作，有望在局部关节炎组织中成像药物摄取。除了药物递送监测外，还将通过与在相同动物上准同时进行的核成像和MRI进行比较来检查SPAT在评估治疗效果方面的独特能力。SPAT通过对滑膜炎的形态学和生理学特征（包括血管增生和缺氧）进行成像，可以实现对关节炎组织对药物治疗的早期反应的综合评价。这项研究预计将开发仪器和技术，可能显着有助于诊断成像和治疗监测各种疾病，包括炎症性疾病和癌症。

DESCRIPTION (provided by applicant): The therapy and diagnosis of diseases at the cellular and molecular levels will be improved greatly with the development of medical imaging technologies that can not only monitor the delivery of analytical probes or therapeutic agents but also enable comprehensive and objective evaluation of treatment effects. As an emerging noninvasive, nonionizing light-based technology presenting both high contrast and high spatial resolution, photoacoustic tomography (PAT) may be developed into a novel and promising molecular imaging modality which will generate innovations and play a critical role in medicine. We propose to investigate an even more advanced spectroscopic PAT (SPAT) technique using inflammatory arthritic disease models, patterned after widely known, very costly, painful, and disabling disorders, for demonstration of the method. SPAT, when aided by a newly developed gold nanocolloid contrast agent, may create innovations with an extensive impact in various biomedical applications, not only in more efficient evaluation of drug effects in living laboratory animals but also in optimized therapeutic decisions in clinical practice. The SPAT system for human/animal inflammatory arthritis will be developed on a stand-alone commercial ultrasound unit which, in an exclusive research mode allows acquisition of light-induced ultrasound signals with 64 independent channels simultaneously. This capability will for the first time enable near real-time 2D PAT and fast speed 3D PAT. Gold nanorods with the optical absorption peak tuned to the NIR region will be conjugated with Etanercept (Enbrel(r)), an FDA approved drug for rheumatoid arthritis. Due to the strong optical absorption by gold nanorods, the SPAT system working with a designed PVDF array transducer holds promise in imaging the drug uptake in regional arthritic tissues. Besides drug delivery monitoring, the unique ability of SPAT in evaluating treatment efficacy will also be examined through the comparison with nuclear imaging and MRI conducted on the same animals quasi-simultaneously. By imaging the morphological and physiological hallmarks of synovitis including hypervascularization and hypoxia, SPAT may realize comprehensive evaluation of the early responses of arthritic tissues to the pharmaceutical treatment. This research is anticipated to develop instrumentation and techniques that may significantly contribute to diagnostic imaging and therapeutic monitoring of various disorders including inflammatory diseases and cancer.