Imaging of Inflammation and Treatment: Basic and Translational Potential

描述(申请人提供)：随着医学成像技术的发展，在细胞和分子水平上对疾病的治疗和诊断将得到极大的改善，医学成像技术不仅可以监测分析探针或治疗剂的输送，还可以对治疗效果进行全面和客观的评估。光声断层成像(PAT)作为一种新兴的非侵入性、非电离光基技术，具有高对比度和高空间分辨率的特点，有望发展成为一种新颖的、有前途的分子成像手段，将产生创新并在医学上发挥关键作用。我们建议使用炎症性关节炎模型来研究一种更先进的光谱PAT(SPAT)技术，该模型模仿众所周知的、非常昂贵的、痛苦的和致残的疾病，以演示该方法。SPAT在新开发的金纳米胶体造影剂的辅助下，可能会在各种生物医学应用中产生广泛影响的创新，不仅在活的实验室动物身上更有效地评估药物效果，而且在临床实践中也会优化治疗决策。人/动物炎症性关节炎的SPAT系统将在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具有独立通道的光诱导超声信号。该功能将首次实现近乎实时的2D PAT和快速3D PAT。光学吸收峰在近红外区域的金纳米棒将与Etanercept(Enbrel(R))结合，Etanercept是FDA批准的治疗类风湿性关节炎的药物。由于金纳米棒的强光吸收，SPAT系统与设计的PVDF阵列换能器配合使用，有望对局部关节炎组织中的药物摄取进行成像。除了药物输送监测外，SPAT在评估治疗效果方面的独特能力也将通过与在同一动物身上几乎同时进行的核成像和核磁共振的比较来检验。SPAT通过成像滑膜炎的形态和生理特征，包括血管增多和缺氧，可以实现对关节炎组织对药物治疗的早期反应的综合评估。这项研究预计将开发可显著有助于各种疾病的诊断、成像和治疗监测的仪器和技术，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.