NSF/FDA SIR: Techniques for Assessing the Performance of Optical Coherence Tomography Systems for Nanoparticle-based Detection of Gastrointestinal Cancers

这项NSF/FDA常驻学者(SIR)提案旨在通过开发基于体模的新测试方法来研究用于检测胃肠道(GI)癌症的纳米颗粒增强光学相干断层扫描(OCT)成像技术。传统的白光内窥镜和活检是目前胃肠道癌症筛查的金标准，但它们存在着高假阴性率导致未发现癌症的问题。OCT提供组织的实时成像，分辨率接近组织病理学。OCT检测胃肠道肿瘤的临床研究前景看好，但肿瘤组织与非肿瘤组织之间的对比度相对较低，限制了其诊断的准确性。最近等离子体纳米粒子的出现为增强胃肠道肿瘤的OCT对比度提供了新的机会。抗体偶联纳米颗粒与癌症生物标记物的分子特异性结合提高了通过OCT靶向内窥镜活检改进临床癌症检测的可能性。纳米颗粒增强OCT成像的发展已经取得了实质性的进展，然而，由于缺乏可靠的、被广泛接受的台式技术来表征图像质量和检测肿瘤病变的能力，创新受到了抑制。因此，OCT系统性能的定量相互比较是有问题的，理解设备、纳米颗粒和组织依赖效应的潜力被削弱。无法使用成熟的技术评估OCT系统也使监管过程复杂化，并增加了制造商提供临床研究以证明安全性和有效性的负担。因此，拟议项目的主要目标是开发和验证新的基于体模的测试方法，使快速和可靠的OCT系统性能评估成为可能，并利用OCT推进纳米颗粒增强的胃肠道癌症检测。代表正常组织和纳米颗粒标记的癌症组织的生物逼真组织模型将被开发出来。将开发基于OCT的样品光学性质测量和纳米颗粒对比度增强估计的技术。此外，还将开发理想化的“公制确定模体”来表征OCT的基本性能参数，如分辨率和灵敏度。将评估通过加入等离子体纳米粒子(例如，金纳米壳)来改善成像性能的潜力。

1135514ChenThis NSF/FDA Scholar-in-Residence (SIR) proposal aims to investigate nanoparticle-enhanced optical coherence tomography (OCT) imaging techniques for detection of gastrointestinal (GI) cancers through the development of novel phantom-based test methods. Conventional white-light endoscopy and biopsy are currently the gold standards for GI cancer screening, however, they suffer from high false-negative rates resulting in undetected cancers. OCT provides real-time imaging of tissues with resolution approaching that of histopathology. Clinical studies of OCT for GI cancer detection are promising, however, the relatively low contrast between neoplastic and non-neoplastic tissues limits its diagnostic accuracy. The recent advent of plasmonic nanoparticles has introduced a new opportunity to enhance OCT contrast for GI cancers. The molecular-specific binding of antibody-conjugated nanoparticles to cancer biomarkers raises the potential for improved clinical cancer detection through OCT-targeted endoscopic biopsy. Substantial progress has been made in the development of nanoparticle-enhanced OCT imaging, however, innovation has been inhibited by a lack of reliable, widely-accepted benchtop techniques for characterizing image quality and the ability to detect neoplastic lesions. As a result, quantitative intercomparison of OCT system performance is problematic and the potential for understanding device-, nanoparticle- and tissue-dependent effects is diminished. The inability to assess OCT systems with wellestablished techniques also complicates the regulatory process and increases the burden on manufacturers to provide clinical studies to demonstrate safety and effectiveness. Therefore, the primaryobjectives of the proposed project are to develop and validate novel phantom-based test methods that will enable rapid and reliable evaluation of OCT system performance and to advance nanoparticle-enhanced detection of GI cancer with OCT. Biologically-realistic tissue phantoms representing normal and nanoparticle-labeled cancerous tissues will be developed. Techniques for OCT-based measurement of sample optical properties and estimation of nanoparticle contrast enhancement will be developed. Additionally, idealized "metric determination phantoms" will be developed to characterize fundamental OCT performance parameters such as resolution and sensitivity. The potential for improving imaging performance by incorporating plasmonic nanoparticles (e.g., gold nanoshells) will be assessed.