We have designed, fabricated, and tested a hexachromatic imager for near-infrared fluorescence image-guided surgery capable of simultaneously imaging three visible and near-infrared spectral channels. The sensor is comprised of 1280 by 720 pixels yielding a 48 dB signal-to-noise-ratio and achieving a minimum indocyanine green concentration detectability of 5 nM. The imaging sensor combines the vertically stacked photodiode technology and an array of pixelated spectral interference filters in a single-chip single-snapshot architecture yielding high sensitivity and clinical translation.
We have created a six-channel multispectral imager for the simultaneous space- and time-detection of color and multiple near-infrared fluorescent molecular markers by integrating the vertically stacked photodetector technology with pixelated spectral interference filters.
Cancer affects one in three people worldwide. Surgery remains the primary curative option for localized cancers, but good prognoses require complete removal of primary tumors and timely recognition of metastases. To expand surgical capabilities and enhance patient outcomes, we developed a six-channel color/near-infrared image sensor inspired by the mantis shrimp visual system that enabled near-infrared fluorescence image guidance during surgery. The mantis shrimp's unique eye, which maximizes the number of photons contributing to and the amount of information contained in each glimpse of its surroundings, is recapitulated in our single-chip imaging system that integrates arrays of vertically stacked silicon photodetectors and pixelated spectral filters. To provide information about tumor location unavailable from a single instrument, we tuned three color channels to permit an intuitive perspective of the surgical procedure and three near-infrared channels to permit multifunctional imaging of optical probes highlighting cancerous tissue. In nude athymic mice bearing human prostate tumors, our image sensor enabled simultaneous detection of two tumor-targeted fluorophores, distinguishing diseased from healthy tissue in an estimated 92% of cases. It also permitted extraction of near-infrared structured illumination enabling the mapping of the three-dimensional topography of tumors and surgical sites to within 1.2-mm error. In the operating room, during surgical resection in 18 patients with breast cancer, our image sensor further enabled sentinel lymph node mapping using clinically approved near-infrared fluorophores. The flexibility and performance afforded by this simple and compact architecture highlights the benefits of biologically inspired sensors in image-guided surgery.
Image-guided surgery (IGS) can improve the patient's outcome by providing meaningful real-time information about the location of cancerous tumors and surrounding tissue, aiding in the elimination of positive tumor margins and reducing iatrogenic damage. However, the clinical need for imaging systems that can provide real-time feedback under real operating room settings remains unmet. State-of-the-art imaging systems for near-infrared fluorescence IGS rely on a series of complex optics and several imaging sensors. As a result, these systems are bulky and expensive, and their architecture lacks the versatility to simultaneously image multiple fluorophores, effectively making them cumbersome when merged into the current surgical workflow. To address these shortcomings, we have designed a multi-spectral imager capable of spatially co-registered hexachromatic vision: three spectral channels in the visible spectrum for the identification of anatomical features in color and three spectral channels in the near-infrared spectrum for the simultaneous identification of multiple near-infrared fluorescence dyes used in IGS. Our single-chip imaging sensor combines the vertically stacked photodetectors technology with pixelated interference filters to create a multi-spectral imager that can help surgeons make clinically relevant decisions in real time, with an effective resolution of 1280x720x3 photodiodes and a frame rate of 24 FPS. Our imager has the ability to identify different shades of near-infrared fluorescent light, allowing the surgeon to use and differentiate multiple fluorophores as molecular probes with high sensitivity. Pre-clinical data is shown where simultaneous imaging of anatomical features in color, and identification of nerves and cancerous tumors, are achieved using multiple near-infrared fluorescent agents.
We have designed, fabricated, and tested a hexachromatic imager for near-infrared fluorescence image-guided surgery capable of simultaneously imaging three visible and near-infrared spectral channels. The sensor is comprised of 1280 by 720 pixels yielding a 48 dB signal-to-noise-ratio and achieving a minimum indocyanine green concentration detectability of 5 nM. The imaging sensor combines the vertically stacked photodiode technology and an array of pixelated spectral interference filters in a single-chip single-snapshot architecture yielding high sensitivity and clinical translation.
