A Novel, Compact, Wide Field of View, Multiphoton Microscope

描述（由申请人提供）：Laser Biopsy Inc，（LBI）的愿景是提高癌症诊断的速度和质量，同时降低患者风险和成本。LBI正在开发一种新的医学成像系统，该系统将使病理学家能够对手术过程中进行的活检进行实时诊断。大多数癌症诊断是通过在某种形式的图像引导下对可疑病变进行活检，然后对固定和染色的组织进行组织病理学分析来进行的。然而，通过更有效的筛查策略，疾病可以更早地被诊断出来，在这种情况下，癌症通常无法通过成像清楚地区分。在这些条件下，外科医生在活检过程中相对“盲目”地操作，从器官内的“代表性部位”移除一定数量的随机活检，而没有任何实时反馈的益处来靶向具有癌症的器官区域。为了解决目前最先进的癌症护理中的这一主要差距，Laser Biopsy Inc.正在开发一种紧凑型低成本多光子显微镜（MPM）系统，能够在获得活检标本后一分钟内对组织样本进行快速无损分析，而无需任何固定化学品、染料染色或切片机切片。基于多光子的成像技术允许组织的可视化，提供关于组织结构和细胞形态的信息。我们的总体假设是，组织活检的多光子组织病理学可以为外科医生提供实时反馈，从而提高靶向活检的准确性，改善患者的诊断和治疗。该项目旨在开发和演示一种新颖，紧凑的光学设计，用于低成本多光子显微镜，其性能参数达到高端商业系统。LBI设计具有在单次扫描中成像25倍于传统多光子显微镜系统的区域的能力，而不牺牲分辨率或将许多图像“平铺”在一起的需要。此外，该设计利用了最新的光学快速原型技术，并需要最少数量的组件，以降低成本和复杂性。根据目前的部件估计，整个仪器的售价低于10万美元是可以支持的，这相当于比目前的商业系统降低3-6倍的成本。将使用标准化荧光样本和动物组织，对该系统进行评估和测试。将通过直接比较每个等效切片的分辨率、信号强度、穿透深度和成像时间来量化性能。数据将由康奈尔大学兽医学院的外科医生和病理学家进行审查。这项工作将成为第二阶段计划的基础，其中的结果将用于开发一种“即时”病理学仪器，用于在时间紧迫的外科手术中新鲜切除的组织。 公共卫生相关性：一个紧凑的，具有成本效益的，高性能的多光子显微镜将使新切除的组织可视化亚微米分辨率，无需固定，切片或染色。这种成像模式将用于向执行活检的外科医生提供即时反馈，从而提高诊断质量、降低每部分成本、降低手术室成本、降低患者焦虑和固有的存档数字记录。

DESCRIPTION (provided by applicant): Laser Biopsy Inc, (LBI) has a vision of improving the speed and quality of cancer diagnosis with reduced patient risk and reduced cost. LBI is developing a new medical imaging system that will enable pathologists to perform real-time diagnosis of biopsies taken during surgical procedures. Most cancer diagnoses are made by biopsying the suspicious lesions under some form of image guidance, followed by histopathological analysis of the fixed and stained tissue. However, with more effective screening strategies, disease is being diagnosed earlier, and in such cases, cancer is often not clearly distinguishable by imaging. Under these conditions, the surgeon operates relatively "blind" during the biopsy procedure, removing a certain number of random biopsies from "representative sites" within the organ, without the benefit of any real-time feedback to target the areas of the organ with cancer. In order to address this major gap in current state-of-the-art cancer care, Laser Biopsy Inc. is developing a compact low-cost Multiphoton microscopy (MPM) system to enable rapid nondestructive analysis of tissue samples within a minute of obtaining a biopsy specimen, without the need for any fixation chemicals, dye stains, or microtome sectioning. Multiphoton-based imaging technology allows visualization of tissue, providing information both about tissue architecture and cellular morphology. It is our overarching hypothesis that multiphoton histopathology from tissue biopsies can provide real-time feedback to surgeons, thus improving the accuracy of targeted biopsies and improving patient diagnosis and treatment. This project is aimed toward the development and demonstration of a novel, compact optical design for a low cost multiphoton microscope with the performance parameters of a high end commercial system. The LBI design has the ability to image in a single scan an area 25 times that of a conventional multiphoton microscope system without sacrificing resolution or the need for "tiling" many images together. Furthermore, the design makes use of the latest optical rapid prototyping technology and requires a minimal number of components for reduced cost and complexity. Based on current parts estimates, a selling price of sub $100K for the entire instrument is supportable, which amounts to a 3-6 x reduction in cost over current commercial systems. The system will be evaluated and tested against a commercial multiphoton microscope using both standardized fluorescent samples and animal tissue. The performance will be quantified by directly comparing resolution, signal intensity, penetration depth, and imaging time per equivalent section. The data will be reviewed by a surgeon and pathologist from the Veterinary School at Cornell. The work will form the basis for a phase II program, in which the results will be used to develop an "instant" pathology instrument for freshly excised tissue in time-critical, surgical procedures. PUBLIC HEALTH RELEVANCE: A compact, cost-effective, high performance multiphoton microscope will enable the visualization of freshly excised tissue with sub micron resolution, without fixation, sectioning or staining. Such an imaging modality will be used to provide immediate feedback to surgeons performing biopsies with improved quality of diagnosis, reduced cost per section, reduced operating room costs, reduced patient anxiety, and intrinsic archival digital records.