Next Generation Fluorescence Guided Surgery with the C-MOLECULES System

摘要 荧光引导手术（FGS）是一个不断发展的领域，越来越多的采用，有大约十几家公司 FDA批准的吲哚菁绿色灌注成像系统，以及领先的手术器械公司 现在购买这样的系统用于营销。先进的分子探针正在数百个正在进行的 FGS临床试验，结合研究级和改良的商业系统。但每个 FGS系统具有低动态范围和来自一系列源的高背景信号。C- MOLECULES相机系统地设计解决了这两个关键问题， 自适应增益、固有的高数字比特转换以及对波长和时间采样的严格控制。 通过窄带滤波器最大限度地抑制组织自发荧光和室内光背景信号 用两个摄像机中的每一个进行滤波，进一步处理图像以进行减法显示。独特的专利 利用超快时间选通增强照相机工作的技术来进一步使荧光最大化， 环境背景，使用达到每像素单个光子水平的特定检测。该系统将 在硬件和软件中完成，并使用时间门控LED灯进行荧光团激活。制度比较 将完成相对于其他市售产品的背景抑制水平测试。 系统，目标是通过增强背景抑制将对比度提高10倍。分子图像 检测将利用正在研究的荧光蛋白质微剂量抗体，对EGFR表达进行成像 在人类头部和颈部肿瘤中。在皮摩尔浓度下对荧光小体成像能力的确认 将验证浓度的最大灵敏度。系统开发和测试是一个合作项目 DoseOptics和达特茅斯之间的合作，这两家公司在技术开发方面都有杰出的专业知识 和人体试验。该团队拥有出版其工作的历史，领导该领域的研究。 FGS，并提供商业翻译的产品。

ABSTRACT Fluorescence guided surgery (FGS) is a growing field with increasing adoption, having about a dozen companies with FDA cleared systems for perfusion imaging with indocyanine green, and leading surgical device companies now acquiring such systems for marketing. Advanced molecular probes are being tested in hundreds of ongoing clinical trials in FGS, with a combination of research grade and modified commercial systems. However, each FGS system suffers from low dynamic range and high background signals from a range of sources. The C- MOLECULES camera has been systematically designed to solve these two key problems, by having high adaptive gain, inherently high digital bit conversion, and tight control over wavelength and temporal sampling. Suppression of tissue autofluorescence and room light background signals are maximized through narrow band filtering with each of two cameras, further processing the images for subtractive display. A unique patented technology for ultrafast time-gated intensified camera work is utilized to further maximize the fluorescence to ambient background, using specific detection that reaches the level of single photons per pixel. This system will be finalized in hardware and software with time-gated LED lamps for fluorophore activation. System comparison testing for the level of background suppression will be completed relative to other commercially available systems, with a goal of 10x increase in contrast through enhanced background suppression. Molecular image testing will utilize a fluorescent protein affibody that is being studied at microdoses, to image EGFR expression in human head and neck tumors. A confirmation of the ability to image fluorescent affibody at picomolar concentrations will be verified for maximal sensitivity. System development and testing is a collaborative project between DoseOptics and Dartmouth, each of which have outstanding expertise in development of the technology and pilot human trials, respectively. The team has a proven history of publishing their work, leading the field of FGS, and delivering products that are commercially translated.