Wide-Field Quantitative Fluorescence Imaging System

项目摘要 在此快速通道（第一阶段+第二阶段）SBIR应用中，我们将评估准确， 快速、低成本的仪器（qF-ImageTM）设计，用于对绝对浓度进行精确的宽视场成像 的荧光团PpIX（CPpIX）在手术领域的指导脑肿瘤切除术，并证明， 设计符合临床验收所需的定量最终用户规范。在第二阶段，我们将完成 在第一阶段确定的qF-ImageTM设计，采用完整的质量管理体系（QMS）进行设计控制 根据行业法规，生产多达5个功能齐全的qF-ImageTM单元，验证最终的 通过临床可用性和调查数据进行设计，并向FDA申请510 k监管许可。QF- ImageTM概念作为荧光引导手术中NIH基金（R 01 NS 052274 -10; PI：Roberts）的一部分而出现 涉及达特茅斯和多伦多的生物医学工程/光学和神经外科研究小组。洞察力 Surgical Technologies（IST）最近由该合作的高级成员成立，他们带来了 丰富的专业知识。（i）ALA-PpIX荧光引导的 手术已被FDA批准用于高级别胶质瘤，（ii）大量的公司行动已经发生， 荧光引导的手术表明了重要的全球市场（例如，斯特赖克购买NOVADAC， 2017年约7亿美元，并通过手术机器人市场领导者Intuitive整合荧光检测 外科手术），(iii)其他医疗技术公司的兴趣（例如，Medtronic、Zeiss）高，（iv）广泛的临床 结果表明，定量CPpIX的令人信服的优势，定性和主观的视觉 荧光成像，和（v）IST是唯一的风险追求商业化的定量宽领域 CPpIX图像（该技术受9项已授权/待批准专利保护）。事实上，我们的研究级 仪器已部署在>150例脑肿瘤患者中：结果表明PpIX水平 用商业系统不可见的荧光（例如，Zeiss Blue 400）可以用更大的 在白光切除术结束时检测残留病变的灵敏度和特异性， 完全切除肿瘤，包括低级别和高级别癌症。此外，qF-ImageTM还可以 可以被修改以检测（i）其他荧光团，（ii）在切除床下方的深度处的肿瘤，以及（iii）多个 荧光团在同一情况下-功能将在未来的产品中实现。InSight的商业计划 将qF-ImageTM定位为市场上第一款用于CPpIX宽视场成像的产品-绝对 脑肿瘤中PpIX的浓度。

PROJECT SUMMARY In this Fast Track (Phase I + Phase II) SBIR application, we will evaluate feasibility (in Phase I) of an accurate, fast and low-cost instrument (qF-ImageTM) design for accurate wide-field imaging of the absolute concentration of the fluorophore PpIX (CPpIX) in the surgical field for guiding brain tumor resection, and demonstrate that design meets quantitative end-user specifications required for clinical acceptance. In Phase II, we will finalize the qF-ImageTM design identified in Phase I under a full quality management system (QMS) for design-control and in compliance with industry regulations, produce up to 5 fully functional qF-ImageTM units, validate the final design through clinical usability and survey data, and apply to FDA for 510k regulatory clearance. The qF- ImageTM concept arose as part of NIH-funding (R01NS052274-10; PI: Roberts) in fluorescence-guided surgery involving biomedical engineering/optics and neurosurgical research teams at Dartmouth and Toronto. InSight Surgical Technologies (IST) was founded recently by the senior members of this collaboration who bring substantial domain expertise. Commercialization is particularly timely: (i) ALA-PpIX fluorescence-guided surgery has been FDA-approved for high-grade glioma, (ii) substantial corporate moves have occurred in fluorescence-guided surgery indicating a significant global market (e.g., Stryker purchase of NOVADAC for ~$700M in 2017, and incorporation of fluorescence detection by a market leader in surgical robotics, Intuitive Surgical.), (iii) interest from other MedTech companies (e.g., Medtronic, Zeiss) is high, (iv) extensive clinical results demonstrate compelling advantages of quantitative CPpIX over qualitative and subjective visual fluorescence imaging, and (v) IST is the only venture pursuing commercialization of quantitative wide-field CPpIX images (the technology is protected by 9 issued/pending patents). Indeed, our research-grade instrument has been deployed in >150 brain tumor patients: results demonstrate that levels of PpIX fluorescence not visible with commercial systems (e.g., Zeiss Blue 400) can be quantified with greater sensitivity and specificity for detection of residual disease at end of white-light resection, enabling more complete tumor removal, including in low-grade as well as high-grade cancers. Additionally, qF-ImageTM can be modified to detect (i) other fluorophores, (ii) tumor at depth below the resection bed, and (iii) multiple fluorophores in the same case – capabilities to be implemented in future products. InSight’s business plan positions qF-ImageTM as the first product on the market for wide-field imaging of CPpIX – the absolute concentration of PpIX in brain tumor.