Next Generation Fluorescence Guided Surgery with the C-MOLECULES System

使用 C-MOLEECULES 系统的下一代荧光引导手术

• 批准号: 9908533
• 负责人: William Ware
• 金额: $ 29.62万
• 依托单位: DOSEOPTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908533
• 关键词: Adoption; Aminolevulinic Acid; Animals; Attention; Blood Vessels; Cell Surface Receptors; Clinical; Clinical Trials; Computer software; Custom; Detection; Development; Devices; Disease; Electronics; Epidermal Growth Factor Receptor; FDA approved; Fluorescence; Foundations; Generations; Genotype; Goals; Growth; Head and Neck Neoplasms; Housing; Human; Image; Image-Guided Surgery; Immunologics; Immunology; Indocyanine Green; Injections; Intuition; Isosulfan Blue; Legal patent; Light; Lighting; Marketing; Metabolism; Methylene blue; Modeling; Molecular Probes; Names; Normal tissue morphology; Operative Surgical Procedures; Optics; Perfusion; Phase; Photons; Proteins; Publishing; Radiation therapy; Recording of previous events; Research; Sampling; Signal Transduction; Sodium Fluorescein; Software Tools; Source; Surgeon; System; Systems Development; Technology; Testing; Time; Tissues; Tracer; Translating; Translations; Work; base; c new; comparative efficacy; cost; design; digital; dosimetry; first-in-human; fluorescence imaging; fluorescence-guided surgery; fluorophore; image processing; imaging system; improved; interest; metabolic imaging; millisecond; molecular imaging; molecular phenotype; neurosurgery; next generation; off-patent; perfusion imaging; preclinical trial; protoporphyrin IX; prototype; real-time images; software development; symposium; targeted imaging; technology development; tool; tumor; uptake; working group

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.

抽象的 荧光引导手术 (FGS) 是一个不断发展的领域，采用率不断提高，大约有十几家公司 与 FDA 批准的吲哚菁绿灌注成像系统以及领先的手术器械公司合作 现在购买此类系统用于营销。先进的分子探针正在数百个正在进行的测试中 FGS 的临床试验，结合了研究级和修改后的商业系统。然而，每个 FGS 系统面临低动态范围和来自各种来源的高背景信号的问题。 C- MOLECULES 相机经过系统设计，通过具有高 自适应增益、固有的高数字位转换以及对波长和时间采样的严格控制。 通过窄带最大限度地抑制组织自发荧光和室内光背景信号 使用两个相机中的每一个进行过滤，进一步处理图像以进行减色显示。独特的专利 利用超快时间选通强化相机工作技术进一步最大化荧光 环境背景，使用达到每像素单光子水平的特定检测。该系统将 最终确定硬件和软件，并使用时间选通 LED 灯激活荧光团。系统对比 背景抑制水平的测试将相对于其他市售产品完成 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 测试将利用正在研究的微剂量荧光蛋白亲和体，对 EGFR 表达进行成像 在人类头颈肿瘤中。确认皮摩尔荧光亲和体成像能力 将验证浓度以获得最大灵敏度。系统开发和测试是一个协作项目 DoseOptics 和 Dartmouth 之间的合作，双方在技术开发方面都拥有出色的专业知识 分别进行人体试验。该团队在发表其作品方面拥有悠久的历史，在该领域处于领先地位 FGS，并提供商业翻译的产品。