Handheld Two-Photon Microscopy Imager

手持式双光子显微成像仪

• 批准号: 9408288
• 负责人: Youbo Zhao
• 金额: $ 22.5万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9408288
• 关键词: 3-Dimensional; Address; Area; Biological; Biopsy; Clinical; Clinical Investigator; Clinical Trials; Collagen; Complement; Cutaneous Melanoma; Development; Development Plans; Devices; Diagnosis; Dimensions; Disease; Engineering; Fiber; Fluorescence; Generations; Goals; Gold; Hand; Human Engineering; Illinois; Image; Imaging Techniques; Imaging technology; In Situ; Knowledge; Laboratories; Lasers; Lead; Malignant Neoplasms; Memorial Sloan-Kettering Cancer Center; Methods; Microscopy; Molecular; Morphology; NADH; Operative Surgical Procedures; Optical Biopsy; Optics; Oral cavity; Pathologic; Pathologist; Pathology; Performance; Phase; Physiologic pulse; Preparation; Process; Pump; Reporting; Research; Research Personnel; Resolution; Sampling; Signal Transduction; Site; Skin; Source; Specimen; Speed; System; Technology; Testing; Time; Tissue imaging; Translating; Universities; Work; base; clinical application; clinical investigation; clinical optical imaging; commercialization; cost; density; design; disease diagnosis; experience; flexibility; fluorophore; human disease; imaging probe; in vivo; innovative technologies; instrument; light weight; malignant mouth neoplasm; medical specialties; microscopic imaging; miniaturize; multidisciplinary; next generation; novel; optical fiber; optical imaging; physical science; preclinical study; product development; programs; prototype; research and development; research clinical testing; screening; second harmonic; second harmonic generation imaging; submicron; success; tissue phantom; two-photon

Project Summary/Abstract Physical Sciences Inc. (PSI) proposes to develop a handheld two-photon microscopy (TPM) probe that will enable in vivo diagnosis and screening of various diseases, including cancers. This novel, clinically usable TPM instrument will provide three-dimensional (3-D) sub-micron resolution images of tissue pathology in situ. The images generated based on the two-photon excitation signals of intrinsic bio-molecules, such as the two-photon excited fluorescence (TPEF) of endogenous fluorophores and the second-harmonic generation (SHG) of collagen, will render important morphological and molecular information specific to various pathologies. Noninvasive optical biopsy based on two-photon microscopy is considered as the next-generation technology for disease diagnosis and has already been investigated in many pre-clinical studies. However, a suitable clinical TPM instrument has not yet been demonstrated, which is largely due to the technical and cost barriers in developing such a sought-after system. These include difficulty in transmitting high-power broadband femtosecond pulses from the bulky laser to a hand-held probe through a flexible fiber cord; challenges in miniaturizing the imaging probe with no sacrifice of imaging performance; and the high cost of the ultrafast laser source needed for efficient excitation of the nonlinear optical processes. Therefore, this R&D program directly addresses these barriers to widespread clinical use of TPM for noninvasive pathology. A laboratory prototype will be developed in the Phase I to demonstrate feasibility, while further optimization, advanced engineering and clinical testing will be performed in Phase II. Innovative technologies, including the development of a specialty fiber module for delivery of high-power ultrashort pulses and generation of a coherent supercontinuum (SC) based on the fiber-delivered laser pulses, as well as novel technological approaches for building a compact light-weight imaging probe, are being proposed. This will be possible by leveraging the expertise of a multidisciplinary team of investigators from PSI, with a proven track record on developing the next generation clinical devices, a leading research group from University of Illinois at Urbana-Champaign, and experienced clinical researchers and pathologists from Memorial Sloan Kettering Cancer Center.

项目概要/摘要 物理科学公司 (PSI) 提议开发一种手持式双光子显微镜 (TPM) 探针，该探针将 能够对包括癌症在内的各种疾病进行体内诊断和筛查。这种新颖的、临床可用的 TPM 仪器将提供组织病理学的三维 (3-D) 亚微米分辨率图像 现场。基于内在生物分子的双光子激发信号生成的图像，例如 内源荧光团的双光子激发荧光 (TPEF) 和二次谐波 胶原蛋白的生成（SHG），将呈现特定于的重要形态和分子信息 各种病理。 基于双光子显微镜的无创光学活检被认为是下一代 疾病诊断技术，并已在许多临床前研究中进行了研究。然而， 合适的临床 TPM 仪器尚未得到证实，这很大程度上是由于技术和 开发这样一个受欢迎的系统的成本障碍。其中包括传输高功率的困难 通过柔性光纤线将宽带飞秒脉冲从庞大的激光器发送到手持式探头； 在不牺牲成像性能的情况下实现成像探头小型化的挑战；以及高昂的成本 有效激发非线性光学过程所需的超快激光源。所以， 该研发计划直接解决了 TPM 广泛临床应用的这些障碍 病理。第一阶段将开发实验室原型以证明可行性，同时进一步 第二阶段将进行优化、先进工程和临床测试。创新的 技术，包括开发用于传输高功率超短波的特种光纤模块 脉冲和基于光纤传输的激光脉冲生成相干超连续谱（SC），如 以及用于构建紧凑型轻型成像探头的新颖技术方法，正在研究中 建议的。这将通过利用多学科研究团队的专业知识来实现 PSI 在开发下一代临床设备方面拥有良好的记录，这是一项领先的研究 来自伊利诺伊大学厄巴纳-香槟分校的研究小组，以及经验丰富的临床研究人员和 纪念斯隆凯特琳癌症中心的病理学家。