Imaging multiple molecular markers under surgical light illumination

Conference Dates

June 2-6, 2019


Image-guided surgery (IGS) has proved to be an exceptional operational strategy for surgeons – aiding in performing far less invasive and much safer procedures. Among the optical imaging techniques available for IGS, near-infrared fluorescence (NIRF) imaging has been one of the main protagonists in research performed by both industrial and academic laboratories. The development of less toxic and far more specific molecular targeted probes constitutes a potential major improvement in the patient’s surgery outcome by giving the surgeon the ability to make real-time clinically relevant decisions based on molecular labels. NIRF imaging has multiple advantages over visible fluorescence imaging, such as low tissue auto-fluorescence and low tissue scattering and absorption which has enabled capturing fluorescence signals several millimeters deep in the tissue. In addition, the excitation and emission spectra are invisible to the unaided human eye and so do not hamper the clinical workflow.

In this paper, we will describe a novel, high-resolution hexachromatic imager for NIRF imaging suitable for IGS. Our imaging sensor combines an array of vertically stacked CMOS photodetectors with pixelated spectral interference filters. The three-dimensional photodetector array exploits the silicon wavelength-dependent depth absorption coefficient to resolve trichromatic information at each pixel location. The pixelated interference filters following a chessboard layout act as shortpass and longpass filters on half of the pixels, respectively. High optical density is achieved due to a specialized nano-fabrication process where material layers with high and low dielectric constants are stacked. The overall result is a monolithically integrated hexachromatic imager capable of color reconstruction in half of the pixels and NIR-shade sensitivity in the other half of the pixels for multiple NIR fluorophore imaging for IGS.

The image sensor is used in conjunction with two NIRF tumor targeted probes to image murine prostate cancer. We demonstrate that by combining information from both probes, the sensitivity and specificity for detecting cancerous tissue is improved. The imaging system was also translated in the operating room to simultaneously image indocyanine green and methylene blue markers for sentinel lymph node mapping in patients with breast cancer. Data from this clinical study will be presented.

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