VISION

Motivation:

A hallmark of a successful curative-intent cancer surgery is the complete removal of all diseases, both gross and microscopic, with minimal damage to neighboring healthy tissue. Surgical guidance, however, is largely accomplished through visual and tactile feedback, which lacks adequate contrast and sensitivity, often leading to residual disease in the patient. Residual disease (or positive surgical margins) is highly correlated with recurrence and mortality and requires adjuvant treatment, incurring added costs, toxicity, and burden to the patient. 

Recently, fluorescence-guided surgery (FGS)–utilizing molecular-targeted fluorescence contrast agents to label both diseased and healthy cells in vivo–has emerged as a promising solution for enhancing surgical visualization in the operating room. However, conventional optical imaging systems suffer from performance-limiting trade-offs between sensitivity and physical maneuverability, as they rely on bulky and rigid optical components. As a result, practical intraoperative fluorescence imaging with camera systems or laparoscopes is limited to macroscopic (mm-scale) detection of disease. 

Our Solution:

To address these needs in next-generation FGS, we introduce a lens-less and chip-based fluorescence imaging platform, VISION (Versatile Imaging Sensor for Intra-Operative Navigation), capable of highly sensitive intraoperative imaging within a compact form factor for maximal maneuverability in the resection cavity. Our custom-designed image sensor is placed in direct contact with the tissue to capture fluorescence emissions before they diverge, enabling microscopic detection without bulky lenses. Through this approach, the entire imaging system is reduced to a thin planar sensor with integrated optics. Our research has taken a number of directions to enable this technology:

• Developing custom high-sensitivity CMOS image sensors

• Integrating focusing optics such as angle selective gratings in CMOS metal layers, for enhanced resolution.

• Enabling filter-less fluorescence imaging through the use of time-resolved imaging and novel fluorescent up-converting nanoparticles

• Designing thin and planar fluorescence filters to enable multicolor fluorescence imaging for simultaneous imaging of diseased and healthy tissue

References:

• M. Roschelle, R. Rabbani, E. Papageorgiou, H. Zhang, M. Cooperberg, B. A. Stohr, A. Niknejad, M. Anwar, "Multicolor fluorescence microscopy for surgical guidance using a chip-scale imager with a low-NA fiber optic plate and a multi-bandpass interference filter," Biomed. Opt. Express 15, 1761-1776 (2024)🔗

• H. Najafiaghdam, C. Pedroso, NA. Torquato, BE. Cohen, M. Anwar. "Fully Integrated Ultra-thin Intraoperative Micro-imager for Cancer Detection Using Upconverting Nanoparticles" Mol Imaging Biol 25, 168–179 (2023). 

• H. Najafiaghdam, C.C.S. Pedroso, B. E. Cohen, M. Anwar, "Optics-Free Chip-Scale Intraoperative Imaging Using NIR-Excited Upconverting Nanoparticles" in IEEE Transactions on Biomedical Circuits and Systems 

• M. Roschelle, R. Rabbani, E. P. Papageorgiou, H. Zhang, M. Spitzer, A. Niknejad, M. Anwar, "Multi-color On-chip Fluorescence Microscopy for Real-time Surgical Guidance"World Molecular Imaging Conference (WMIC) (2022).

• A. Gharia, E.P. Papageorgiou, S. Giverts, C. Park, M. Anwar, "Signal to Noise Ratio as a Cross-Platform Metric for Intraoperative Fluorescence Imaging". Mol Imaging. 2020.

• E. P. Papageorgiou, B. E. Boser and M. Anwar, "Chip-Scale Angle-Selective Imager for In Vivo Microscopic Cancer Detection," in IEEE Transactions on Biomedical Circuits and Systems, 2020.

• Wong, J. M., Papageorgiou, E. P., Giverts, S., Park, C., & Anwar, M. (2019, February). Feasibility of Breast Tumor Imaging in a Mouse Model Using Angle Selective Fluorescence Contact Imaging. In ANNALS OF SURGICAL ONCOLOGY.

• Najafiaghdam H, Papageorgiou E, Torquato NA, Tian B, Cohen BE, Anwar M. "A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination". in Theranostics.

• E.P. Papageorgiou, H. Zhang, B.E. Boser, C. Park, M. Anwar, "Angle-insensitive amorphous silicon optical filter for fluorescence contact imaging," Opt. Lett. 43, 354-357 (2018)

• E. P. Papageorgiou, S. Giverts, H. Zhang, C. Park, B. E. Boser and M. Anwar, "Imaging of IR700DX Labeled Mouse Breast Tumor Using a Custom Angle-Selective Fluorescence Contact Imaging System," 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

• H. Najafiaghdam, E.P. Papageorgiou, N.A. Torquato, C.A. Tajon, H. Zhang, C. Park, B. Boser, B.E. Cohen, M. Anwar, "A Molecular Imaging "Skin" A Time-resolving Intraoperative Imager for Microscopic Residual Cancer Detection Using Enhanced Upconverting Nanoparticles," 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

• E.P. Papageorgiou, B.E. Boser, M. Anwar, "An angle-selective CMOS imager with on-chip micro-collimators for blur reduction in near-field cell imaging" in IEEE 29th International Conference on Micro Electro Mechanical Systems (MEMS)