The staging of solid cancers is critical to the planning of both primary treatment with surgery and adjuvant therapies like chemotherapy; however, staging is not always possible with preoperative information and may require intraoperative evaluation of sentinel lymph nodes to confirm or disaffirm the presence of metastasis. Challenges are presented by standard-of-care sentinel lymph node dissection which must be quick and accurate enough to guide the surgical strategy despite a workflow that stretches from the operating room to the pathology lab; however, a solution is posed by fluorescence-assisted sentinel lymph node dissection which uses fluorescent probes to communicate the location and/or status of sentinel lymph nodes, reducing the complexity of the surgery and/or eliminating the need for rapid pathology. In support of this emerging modality, we have constructed a snapshot hyperspectral imaging system with sensitivity from the far-red to the near-infrared that enables sentinel lymph node dissection with multiple near-infrared fluorophores. We have also developed a spectral unmixing routine for in vivo quantification of the readily available fluorophores indocyanine green and methylene blue that can be extended to emerging fluorophores that actively target tumor cells. Both the imaging system and the unmixing routine have been tested in a clinical setting where they have successfully discriminated two dyes exhibiting different distributions.
Multi-spectral and polarization imaging have enabled and exploited a wide range of applications, from remote sensing to biomedical applications such as early cancer detection for image-guided surgery. However, state-of-the-art multispectral and polarization cameras are still based on conventional advances in optics and integrated circuits, yielding bulky form factors and poor signal reconstruction. Thus, these technologies have failed to be adopted as research or clinical imaging tools. Nature is full of examples of animals that take advantage of multi-spectral and polarization phenomena to gain an evolutionary advantage. For example, elegant low-power and compact biological visual systems, capable of multispectral and polarization imaging surpassing any man-made imaging system, can be found in the compound eyes of many arthropods. Here, we demonstrate radically novel, multi-spectral and polarization imaging sensors that function on the same fundamental principles as do the ommatidia of the mantis shrimp. Our bio-inspired imaging systems combine vertically stacked photodiodes, for single-pixel trichromatic vision, with an array of pixelated polarization filters, resulting in compact and low-power architectures. Our single-chip imager comprises of 1280-by-720 pixels, yielding a 62 dB and 48 dB dynamic range and signal-to-noise ratio, respectively, and operates at a maximum frame rate of 24 fps. This topology inherently co-registers in time and space the different spectral and polarization channels. This novel and ergonomic technology is enabling real-time in situ underwater polarization imaging as well as applications in biomedical fields.
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.
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