Ultrathin and flexible 4-channel scope for guiding surgical resections using a near-infrared fluorescence molecular probe for cancer

摘要

Minimally-invasive optical imaging is being advanced by molecular probes that enhance contrast using fluorescence. The applications in cancer imaging are very broad, ranging from early diagnosis of cancer to the guiding of interventions, such as surgery. The high-sensitivity afforded by wide-field fluorescence imaging using scanning laser light is being developed for these broad applications. The platform technology being introduced for fluorescence-guided surgery is multimodal scanning fiber endoscope (mmSFE), which places a sub.1-mm optical fiber scanner at the tip of a highly flexible scope. Because several different laser wavelengths can be mixed and scanned together, full-color reflectance imaging can be combined with near infrared (NIR) fluorescence imaging in a new 4-channel multimodal SFE. Different imaging display modes are evaluated to provide surgeons fluorescence information with anatomical background preserved. These preliminary results provide a measure of mmSFE imaging performance in vitro and ex vivo, using a mouse model of brain cancer and BLZ.100 fluorescence tumor indicator. The mmSFE system generated wide-field 30 Hz video of concurrent reflectance and NIR fluorescence with sensitivity below 1 nM in vitro. Using the ex vivo mouse brain tumor model, the low-power 785-nm laser source does not produce any noticeable photobleaching of tumors with strong fluorescence signal over 30 minutes of continuous multimodal imaging. The wide-field NIR fluorescence images of the mouse brain surface produced a match to the conventional histology slices by processing the hematoxylin signal in a mean intensity projection to the outer surface and then registering with the mmSFE image. These results indicate the potential for the mmSFE and BLZ.100 tumor indicator for fluorescence guidance of keyhole neurosurgery.