Abstract
Image-guided surgery can enhance cancer treatment by decreasing, and ideally eliminating, positive tumor margins and iatrogenic damage to healthy tissue. Current state-of-the-art near-infrared fluorescence imaging systems are bulky and costly, lack sensitivity under surgical illumination, and lack co-registration accuracy between multimodal images. As a result, an overwhelming majority of physicians still rely on their unaided eyes and palpation as the primary sensing modalities for distinguishing cancerous from healthy tissue. Here we introduce an innovative design, comprising an artificial multispectral sensor inspired by the Morpho butterfly's compound eye, which can significantly improve image-guided surgery. By monolithically integrating spectral tapetal filters with photodetectors, we have realized a single-chip multispectral imager with 1000 × higher sensitivity and 7 × better spatial co-registration accuracy compared to clinical imaging systems in current use. Preclinical and clinical data demonstrate that this technology seamlessly integrates into the surgical workflow while providing surgeons with real-time information on the location of cancerous tissue and sentinel lymph nodes. Due to its low manufacturing cost, our bio-inspired sensor will provide resource-limited hospitals with much-needed technology to enable more accurate value-based health care.
Highlights
Surgery is the primary curative option for patients with cancer, with the overall objective of complete resection of all cancerous tissue while avoiding iatrogenic damage to healthy tissue
The fixed pattern noise for all four channels is evaluated under 30 ms exposure and different illumination intensities, ranging from dark conditions to intensities that almost saturate the pixel’s output signal
The spatial variations in the optical response of the tapetal filters are primarily due to variations in the underlying transistors and photodiodes within individual pixels, which can be mitigated via calibration, improving spatial uniformity under various illumination conditions
Summary
Surgery is the primary curative option for patients with cancer, with the overall objective of complete resection of all cancerous tissue while avoiding iatrogenic damage to healthy tissue. The clinical need for imaging instruments that provide real-time feedback in the operating room is unmet, largely due to the use of imaging systems based on contemporary technological advances in the semiconductor and optical fields, which have bulky and costly designs with suboptimal sensitivity and co-registration accuracy between multimodal images [3,4,5,6,7]. We demonstrate that image-guided surgery can be dramatically improved by shifting the design paradigm away from conventional advancements in the semiconductor and optical technology fields and instead adapting the elegant 500-million-year-old design of the Morpho butterfly’s compound eye [8,9]: a condensed biological system optimized for highacuity detection of multispectral information. Our bio-inspired image sensor has the prominent advantages of (1) capturing both color and near-infrared fluorescence (NIRF) with high co-registration accuracy and sensitivity under surgical light illumination, allowing simultaneous identification of anatomical features and tumor-targeted molecular markers; (2) streamlined design—at 20 g including optics, our bio-inspired image sensor does not impede surgical workflow; and (3) low manufacturing cost of ~$20, which will provide resource-limited hospitals with much-needed technology to enable more accurate value-based health care
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