Two-Photo Optical Biopsy Probe

双光光学活检探头

• 批准号: 6439150
• 负责人: Peter T. So
• 金额: $ 48.11万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6439150
• 关键词: bioengineering /biomedical engineering; bioimaging /biomedical imaging; biomedical equipment development; biopsy; clinical research; cytology; extracellular matrix; fluorescence; human tissue; image processing; imaging /visualization /scanning; lasers; microscopy; miniature biomedical equipment; neoplasm /cancer diagnosis; optics; portable biomedical equipment

DESCRIPTION (provided by applicant): Two-photon microscope is a powerful tool for in vivo imaging of cellular and extracellular matrix structures with sub-micron resolution. Two-photon based non-invasive optical biopsy methods have the potential of being used as an adjunct to excisional biopsy and histopathology. While the utility of two-photon microscopy for biological studies has been clearly demonstrated in areas such as neurobiology and embryology, its clinical potential remains unrealized. The operational complexity, size, imaging speed and cost stand in the way of testing this new technology in a clinical setting. This proposal addresses these difficulties by engineering a compact two-photon optical biopsy probe. A hand-held device will be built to image tissue cellular structures at video rate (> 10 frames/sec) with sub-cellular resolution down to a depth of 150-200 -1. A number of preliminary studies have been completed to demonstrate the feasibility of this project. (1) The use of two- photon excitation to image tissue cellular structures and metabolism based on its autofluorescence was demonstrated, Preliminary data indicating this technique's potential to distinguish normal and malignant tissues are included. (2) A prototype video-rate two-photon microscope was constructed. (3) A confocal reflected-light imaging sub-system was incorporated into a two-photon microscope. (4) The distribution of tissue biochemical constituents has been resolved based on their two-photon spectra. (5) The key two-photon photodamage mechanisms were identified, The aim of this proposal is to develop a hand-held two-photon biopsy probe suitable for clinical research. We will study the engineering challenges associated with miniaturizing two-photon technology such as the delivep ultra-short light pulses. It is also critical to avoid tissue photodamage; the maximum perr&sibl.e laser power and dosage levels will be established. We will characterize the performance this device in tissue phantoms, animal models and excised human skin biopsy specimens. We hope that the successful completion of this project will result in a first generation device that will allow the evaluation of two-photon optical biopsy techniques in the clinics.

描述（由申请人提供）： 两光子显微镜是具有亚微米分辨率的细胞和细胞外基质结构的体内成像的强大工具。基于两光子的非侵入性光学活检方法具有被用作移动活检和组织病理学辅助的潜力。尽管两光子显微镜在生物学研究中的效用已在 神经生物学和胚胎学等领域，其临床潜力仍未实现。操作的复杂性，大小，成像速度和成本以在临床环境中测试这项新技术的方式。该建议通过工程设计紧凑的两光活检探针来解决这些困难。将建造手持设备，以视频速率（> 10帧/秒）对组织细胞结构进行成像，并以亚细胞分辨率降至150-200 -1的深度。已经完成了许多初步研究，以证明该项目的可行性。 （1）使用两个光子激发图像组织细胞 证明了基于自身荧光的结构和代谢，初步数据表明该技术可以区分正常组织和恶性组织。 （2）构建了原型视频速率两光子显微镜。 （3）将共聚焦反射光成像子系统纳入了两光子显微镜。 （4）组织生化成分的分布已根据其两光谱光谱解决。 （5）确定了关键的两光子光损伤机制，该建议的目的是开发适合临床研究的手持式两光活检探针。我们将研究与小型化两光子技术相关的工程挑战，例如Delivep Ultra-Short轻脉冲。避免组织光损伤也很重要。最大 将建立Perr＆Sibl.E激光功率和剂量水平。我们将在组织幻像，动物模型和切除的人类皮肤活检标本中表征该设备的性能。我们希望该项目的成功完成将导致第一代设备，该设备将允许评估诊所中的两光活检技术。