Innovative high throughput tunable filter for widefield biomedical Raman imaging

描述（由申请人提供）：术中成像技术被神经外科医生用于治疗原发性脑肿瘤，如胶质瘤，以实现最大程度的手术切除病理组织，同时保持基本区域完整。目前的成像技术包括磁共振成像（MRI）、计算机断层扫描（CT）、x射线透视和超声波。由于MRI的尺寸、成本和大量的图像采集时间、CT和x线透视的电离辐射风险、匹配介质接触的要求和超声分辨率差，限制了它们的广泛应用。此外，所有这些技术都不足以识别留在切除床上的最后残留细胞。Agiltron与美国韦恩州立大学（Wayne State University）合作，提出开发一种强大、敏感、选择性和低成本的拉曼图像设备，用于组织的分子诊断，促进术中诊断和肿瘤边缘评估。拉曼成像是一种光学技术，提供定量和特定键的结构信息，因此能够检测细微的

DESCRIPTION (provided by applicant): Intraoperative imaging techniques are used by neurosurgeons in the treatment for primary brain tumors such as gliomas to achieve maximal surgical resection of pathological tissue while leaving essential areas intact. Current imaging techniques include magnetic resonance imaging (MRI), computed tomography (CT), x-ray fluoroscopy, and ultrasound. Their wide use is inhibited by the size, cost, and significant image acquisition time of MRI, the ionizing radiation risk of CT and x-ray fluoroscopy, the requirement of matching medium contact and poor resolution of ultrasound. Furthermore, all of these techniques are inadequate to identify the last residual cells that remain in the resection bed. Agiltron, in collaboration with Wayne State University, proposes to develop a robust, sensitive, selective, and low cost Raman image device for molecular diagnostics of tissue and facilitate intraoperative diagnosis and tumor margin assessment. Raman imaging is an optical technique that offers quantitative and bond-specific structural information and is thus able to detect subtle biochemical differences between the tissue samples. It is non-invasive and can be performed in vivo to provide a real-time diagnosis. The key innovation of our approach is to develop novel wavelength-tunable near infrared filters that have large clear aperture, fine continuous tuning resolution, excellent stability and high dynamic range. This advanced design offers a multiplicity of attributes that overcome the deficiencies associated with conventional approaches. The integration of this high throughput tunable filter into a wide field Raman imaging system will enable us to acquire high signal-to-noise ratio, high spectral resolution, and high spatial resolution Raman images with acquisition times an order of magnitude shorter than existing systems. Furthermore, the large clear aperture of the filter will enable us to acquire Raman images with a field-of-view and working distance comparable to those of intraoperative surgical fluorescence cameras. The proposed Raman imaging system has the potential to offer a superior solution for intraoperative tumor margin delineation than existing fluorescence based systems without the need to administrate contrast agents and not being affected by the presence of tissue auto-fluorescence. The specific aims of the Phase I research are: 1) Design, fabricate and test the integrated tunable filters. 2) Assemble a prototype wide field Raman imaging system with long working distance and large imaging area. 3) Acquire high quality Raman images of in-vitro normal brain tissues and tumors. 4) Demonstrate that the images can be used to differentiate tumors from normal tissues with high sensitivity and high specificity.