Development of a Wearable Fluorescence Imaging Device for IntraoperativeIdentification of Brain Tumors

开发用于术中识别脑肿瘤的可穿戴荧光成像装置

• 批准号: 10697009
• 负责人: Guoqiang Yu
• 金额: $ 102.79万
• 依托单位: BIOPTICSTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-25 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697009
• 关键词: Agreement; Aminolevulinic Acid; Award; Biopsy Specimen; Blinded; Bluetooth; Brain Neoplasms; Calibration; Characteristics; Clinical; Clinical assessments; Color; Conventional Surgery; Data; Detection; Development; Devices; Diagnosis; Diffuse; Dyes; Ensure; Equilibrium; Equipment; Excision; Eye; Feedback; Fluorescein; Fluorescence; Fluorescent Dyes; Funding; Hand; Hospitals; Image; Imaging Device; Intracranial Neoplasms; Kentucky; Legal patent; Malignant Glioma; Malignant Neoplasms; Marketing; Mechanics; Methylene blue; Microscope; Movement; Neurosurgeon; Normal tissue morphology; Notification; Obstruction; Operative Surgical Procedures; Ophthalmologic Surgical Procedures; Outcome; Patient-Focused Outcomes; Patients; Performance; Persons; Phase; Price; Primary Brain Neoplasms; Raspberry Pi; Resected; Sales; Side; Site; Small Business Technology Transfer Research; Surgeon; Survival Rate; System; Techniques; Technology; Testing; Time; Tissues; Touch sensation; Tracer; United States; Visualization; Weight; brain tumor resection; cancer imaging; commercialization; cost; design; flexibility; fluorescence imaging; fluorescence microscope; fluorescence-guided surgery; imaging system; improved; innovation; manufacture; miniaturize; neoplastic cell; neurosurgery; operation; patient safety; portability; prototype; tumor; wearable device; wireless; wireless fidelity

ABSTRACT Approximately 700,000 people in the United States are diagnosed with a primary brain tumor. Of these, malignant gliomas (MGs) account for approximately 40% of all intracranial tumors, with an overall survival rate of only ~34%. Surgical resection remains the cornerstone of therapy and the extent of resection correlates with survival. Fluorescence imaging has emerged as an adjunctive technique, allowing for real-time cancer-specific detection. Surgeries guided by fluorescence imaging achieve gross-total-resection (GTR) rates of 75-100%, which are significantly higher than conventional surgeries with GTR rates of 30-55%. However, most clinical-grade imaging systems are hampered by high costs, limited portability, and lack of operation flexibility. Some neurosurgical fluorescence microscopes cost upwards of ~$500K and weigh ~800 pounds (PENTERO® 900 with fluorescence kits, Carl Zeiss). Many surgeons prefer, and continue to use wearable surgical eye loupes, which allow for convenient and fast operation, but are not capable of fluorescence visualization. Supported by the STTR Phase 1 Award (R41CA243600) and Kentucky State Matching Fund, Bioptics Technology (BOT) has developed a low- cost wearable FLoupe™ device (US Patent Application #62/530,613, 2017) attached to surgical eye loupes for intraoperative identification of fluorescent MGs. We have tested FLoupe™ prototypes to image fluorescent MGs during surgery in a small group of patients. Comparable results are observed against the PENTERO® 900 system. Based on neurosurgeons’ feedback in Phase 1, this Phase 2 project will further optimize the headlights (LEDs), video camera, emission filters, electrical control system, and mechanical design of the FLoupe™ device in terms of weight, size, imaging quality, and ease to wear/operate (Aim 1). The optimized FLoupe™ device will be calibrated and validated against the PENTERO® 900 system for equivalence to image fluorescent MGs in a large group of patients (Aim 2). We expect that fluorescence images taken at the surgical site and from biopsied samples by both devices will be equivalent and agree with the blinded histopathological analyses (the gold standard). Resulting data will be used for FDA clearance via the pre-market notification 510(k) submission with the PENTERO® 900 system as the primary predicate. Compared to the PENTERO® 900 system, the FLoupe™ device is significantly less expensive (<$10K unit sale price), more compact (wearable), and easier to operate (hand free with wireless control). This affordable and wearable device will significantly increase the ability of neurosurgeons to conduct fast and thorough operations, thus improving patient safety and outcomes. At the end of this Phase 2, a clinical-grade FLoupe™ device will be generated as a pre-manufactured product for intraoperative identification of MGs. Moreover, the FLoupe™ device with a modular design is easily modified with optimized excitation lights and emission filters to image a variety of visible dyes (e.g., fluorescein, 5-ALA, methylene blue). Thus, our product has the potential to be incorporated in other surgical settings beyond brain tumor resection based on the fluorescence characteristics of cancers, thereby expanding its market share.

抽象的 在美国，大约有 70 万人被诊断患有原发性脑肿瘤。 神经胶质瘤 (MG) 约占所有颅内肿瘤的 40%，总体生存率仅为 ~34%。手术切除仍然是治疗的基石，切除范围与生存率相关。 荧光成像已作为一种辅助技术出现，可以进行实时癌症特异性检测。 荧光成像引导的手术实现了 75-100% 的大体全切除 (GTR) 率， 显着高于传统手术，GTR 率为 30-55%，但大多数临床级成像。 一些神经外科系统受到成本高、便携性有限和缺乏操作灵活性的阻碍。 荧光显微镜的成本高达约 50 万美元，重量约 800 磅（带荧光的 PENTERO® 900） 套件，卡尔蔡司）许多外科医生更喜欢并继续使用可穿戴式手术眼放大镜，这样可以进行手术。 操作方便快捷，但不支持 STTR 相支持的荧光可视化。 1 奖 (R41CA243600) 和肯塔基州配套基金，Bioptics Technology (BOT) 开发了一种低 成本可穿戴式 FLoupe™ 设备（美国专利申请#62/530,613，2017）连接到手术眼科放大镜，用于 荧光 MG 的术中识别 我们已经测试了 FLoupe™ 原型来对荧光 MG 进行成像。 在一小群患者的手术过程中观察到与 PENTERO® 900 相当的结果。 根据第一阶段神经外科医生的反馈，第二阶段项目将进一步优化前灯。 (LED)、摄像机、发射滤光片、电气控制系统和 FLoupe™ 设备的机械设计 优化后的 FLoupe™ 设备将在重量、尺寸、成像质量和佩戴/操作方便性方面实现卓越的性能提升。 针对 PENTERO® 900 系统进行校准和验证，与荧光 MG 成像等效 我们期望在手术部位和活检中获取荧光图像。 两种设备的样本将是等效的，并且与盲法组织病理学分析一致（黄金 结果数据将通过上市前通知 510(k) 提交用于 FDA 审批。 PENTERO® 900 系统作为主要谓词 与 PENTERO® 900 系统相比，FLoupe™。 设备的价格明显便宜（单价<10K 美元）、更紧凑（可穿戴）且更易于操作 （解放双手，无线控制）。这种经济实惠的可穿戴设备将显着提高操作能力。 神经外科医生进行快速彻底的手术，从而最终提高患者的安全和结果。 在第二阶段中，将生成临床级 FLoupe™ 设备作为预制产品，用于 此外，FLoupe™ 装置采用模块化设计，易于修改。 具有优化的激发光和发射滤光片，可对各种可见染料（例如荧光素、5-ALA、 亚甲蓝）因此，我们的产品有潜力应用于脑以外的其他手术环境中。 根据癌症的荧光特征进行肿瘤切除，从而扩大其市场份额。