Protease chain reactions for molecular analysis of cancer markers

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 CTand 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 notbeing 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 andlarge 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. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The proposed compact, robust, and low cost chemical imaging system has the potential to replace the labor-intense and time consuming conventional methods to diagnose diseased tissue and would make the diagnosis more accurate, faster, and at lower cost.