A bio-inspired, asynchronous, time-domain, multispectral imaging system for high dynamic range near-infrared fluorescence image-guided surgery

As surgery has become the standard-of-care for cancer, surgeons have been left underequipped to identify tumors in the operating room, causing many operations to end in positive margins and necessitating secondary treatments to remove remaining tumor tissue. Near-infrared fluorescence image-guided surgery utilizes near-infrared fluorescent markers and near-infrared sensitive cameras to highlight cancerous tissues. Unfortunately, state-of-the-art imaging systems are unable to handle the high dynamic range between strong surgical lighting and weak fluorescent emission and suffer from temperature-dependent co-registration error. To provide a cost-effective and space-efficient imaging system with sufficient dynamic range and no co-registration error, this work analyzes the required dynamic range for a single-sensor imaging system used for near-infrared fluorescence image-guided surgery and reports the development of a single-chip snapshot multispectral imaging system that meets this specification. By monolithically integrating an asynchronous time-domain image sensor and pixelated interference filters, this system achieves a dynamic range of 120 dB without co-registration error in four channels across the visible and near-infrared spectra. The imager can detect less than 100 nM of the FDA-approved fluorescent dye indocyanine green under surgical lighting conditions, making it a promising candidate for image-guided surgery clinical trials