Development of Medical Multiphoton Microscopic Endoscopy

描述（由申请人提供）：这个生物工程研究伙伴关系的最终目标是通过实现体内组织内在诊断特性的实时、原位生物物理显微成像，在公共卫生保健的医学内窥镜功能有效性方面取得重大进展。多光子显微镜（MPM）在组织图像中产生的荧光和二次谐波，无需外部标记，有望有效地利用MPM内窥镜在体内检测和诊断识别疾病，如癌症、胶原结构损伤和纤维化疾病状态等。MPM内窥镜将利用生物物理实验室研究中发现和分析的MPM成像能力，包括活体制剂和显示各种疾病状态的转基因模型动物，并通过组织学验证。MPM是通过PI和康奈尔大学的主要人员的相关研究项目发明并继续发展的，现在是康奈尔大学的威尔医学院。第一个基本目标是开发用于人类医学的数据基础，将新鲜医学活检的MPM图像与合作病理学家的组织学和临床诊断进行评估和验证进行比较，从而在Weill医学实验室生产诊断性MPM图像地图集，以供最终传播。为了通过MPM内窥镜实现MPM组织成像能力从实验室到医疗应用的转变，康奈尔威尔医疗中心的一群具有代表性的内科医生和外科医生聚集在一起，在他们不同的专业中测试和评估这种能力。同时，一个重要的目标是开发超小型化，可靠的MPM内窥镜装置，与人体生理各器官所需的各种几何形状兼容，这可以与更容易获得的设计并行，以装备更大规模的内窥镜。尽管已经发表了一些先祖，但仪器仪表构成了该计划的主要发展挑战。为了实现这一目标，我们在超快光学和纳米结构制造方面建立了专业知识的关键人员进行创新研究，以设计，制造和测试潜在的系统。安装在内窥镜设备中的显微镜组件的生物医学工程需要进行测试，最终在人类MPM内窥镜应用中，最初由我们的合作MD进行。最后，需要向商业制造商转让技术，以提供医疗器械的可用性，以实现这一最终目标：新的医疗能力。

DESCRIPTION (provided by applicant): The ultimate objective of this Bioengineering Research Partnership is creation of significant advances in the functional effectiveness of medical endoscopy for public health care by enabling the real-time, in situ incorporation of the biophysical micro-imaging of the intrinsic diagnostic properties of tissue in vivo. The fluorescence and second harmonic generation in tissue images by multiphoton microscopy (MPM) without the need for extrinsic labeling are expected to enable effective medical utilization of the capabilities of MPM for in vivo detection and diagnostic recognition of maladies such as cancers, collagen structure damage, and fibrotic disease states, etc., by MPM Endoscopy. MPM Endoscopy will utilize the MPM imaging capabilities discovered and analyzed in biophysical laboratory research, including living preparations, and transgenic model animals displaying various disease states - with validation by histology. MPM was invented and continues to be advanced through associated research programs of the PI and key personnel at Cornell University, and now with Weill Medical College of Cornell University. The first essential aim is development of the data foundation for use in human medicine with MPM images of fresh medical biopsies compared to their appraisal and validation by collaborating pathologists' histology and clinical diagnoses, leading to production of atlases of diagnostic MPM images at Weill Medical's laboratory for eventual dissemination. To accomplish this transition of the MPM tissue imaging capabilities from the laboratory to medical application via MPM endoscopy, a representative cadre of physicians and surgeons at Cornell Weill Medical have assembled to partner in testing and evaluating this capability in their diverse specialties. Simultaneously, an essential aim is development of hyper-miniaturized, reliable MPM endoscopic apparati compatible with the diverse geometries required for various organs of human physiology, which can progress in parallel with more accessible designs for equipping of larger scale endoscopies. Despite published progenitors, instrumentation comprises the major developmental challenge of the program. To accomplish this objective, innovative research by our key personnel with established expertise in ultrafast optics and nanostructure fabrication is invoked to design, fabricate and test potential systems. Biomedical engineering of microscopy components installed in endoscopy apparati is required for testing, ultimately in human MPM Endoscopy applications initially by our collaborating MD's. Finally, technology transfer to commercial manufacturers to provide medical instrument availability is required to achieve the ultimate objective of this: new medical capability.