Innovative high throughput tunable filter for widefield biomedical Raman imaging

描述(申请人提供)：神经外科医生在治疗原发脑肿瘤(如胶质瘤)时使用术中成像技术，以实现最大限度地手术切除病理组织，同时保持必要区域的完整。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。MRI的体积、成本和图像采集时间、CT和X射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低等因素制约了它们的广泛应用。此外，所有这些技术都不足以识别保留在切除床上的最后残留细胞。安捷伦与韦恩州立大学合作，计划开发一种坚固、灵敏、选择性和低成本的拉曼成像设备，用于组织的分子诊断，并促进术中诊断和肿瘤边缘评估。拉曼成像是一种光学技术，它提供定量的和特定于键的结构信息，因此能够检测到细微的 组织样本之间的生化差异。它是非侵入性的，可以在体内进行，以提供实时诊断。该方法的关键创新之处在于研制了新型的波长可调近红外滤光片，它具有大的透明孔径、良好的连续调谐分辨率、良好的稳定性和高动态范围。这种先进的设计提供了多种属性，克服了与传统方法相关的缺陷。将这种高通量可调谐滤光片集成到广视场拉曼成像系统中，将使我们能够获得高信噪比、高光谱分辨率和高空间分辨率的拉曼图像，其采集时间比现有系统短一个数量级。此外，滤光片的大口径将使我们能够获得与手术中荧光摄像机相当的视场和工作距离的拉曼图像。与现有的基于荧光的系统相比，提出的拉曼成像系统有可能为术中勾画肿瘤边缘提供更好的解决方案，而不需要使用造影剂，也不受组织自动荧光的影响。第一阶段研究的具体目标是：1)设计、制造和测试集成可调谐滤波器。2)组装了一台工作距离远、成像面积大的广视场拉曼成像系统样机。3)获得高质量的体外正常脑组织和肿瘤的拉曼图像。4)证明该图像具有较高的灵敏度和特异度，可用于区分肿瘤和正常组织。

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.