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

描述(由申请人提供)：激光活组织检查公司(LBI)的愿景是提高癌症诊断的速度和质量，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的活检进行实时诊断。大多数癌症的诊断是通过在某种形式的图像引导下对可疑的病变进行活组织检查，然后对固定的和染色的组织进行组织病理学分析。然而，随着更有效的筛查策略，疾病被更早地诊断出来，在这种情况下，癌症通常不能通过成像清楚地区分开来。在这种情况下，外科医生在活组织检查过程中进行相对“盲目”的操作，从器官内的“代表性部位”移除一定数量的随机活组织检查，而没有任何实时反馈的好处，以针对患有癌症的器官区域进行定位。为了解决当前最先进的癌症护理中的这一重大缺口，激光活检公司正在开发一种紧凑、低成本的多光子显微镜(MPM)系统，能够在获得活检样本后一分钟内对组织样本进行快速非破坏性分析，而不需要任何固定剂、染料或切片切片。基于多光子的成像技术可以对组织进行可视化，提供有关组织结构和细胞形态的信息。我们的首要假设是，来自组织活检的多光子组织病理学可以向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型的、紧凑的光学设计，用于低成本的多光子显微镜，其性能参数达到高端商业系统的性能参数。LBI的设计能够在一次扫描中成像25倍于传统多光子显微镜系统的区域，而不会牺牲分辨率，也不需要将许多图像“拼接”在一起。此外，该设计利用了最新的光学快速成型技术，并需要最少的组件数量，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了3-6倍的成本。该系统将使用标准荧光样本和动物组织在商用多光子显微镜上进行评估和测试。性能将通过直接比较分辨率、信号强度、穿透深度和每个等效截面的成像时间来量化。康奈尔大学兽医学院的外科医生和病理学家将审查这些数据。这项工作将形成第二阶段计划的基础，在该计划中，结果将用于开发一种用于在时间关键的外科手术中对新鲜切除组织进行“即时”病理检查的仪器。 与公共健康相关：紧凑、经济实惠、高性能的多光子显微镜将能够以亚微米的分辨率可视化新切除的组织，而不需要固定、切片或染色。这种成像方式将被用来向进行活检的外科医生提供即时反馈，提高诊断质量，降低每一节的成本，降低手术室成本，减少患者焦虑，以及内在的档案数字记录。

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.