The HÈRMES project is situated in the rapidly evolving field of time-resolved optical imaging, where the ability to capture ultrafast light signals with extreme sensitivity has the potential to transform biomedical diagnostics and image-guided interventions. Time-Correlated Single Photon Counting (TCSPC) is widely recognized as a non-invasive and highly precise technique capable of reconstructing the temporal profile of extremely faint optical signals with high fidelity. It has gained a prominent role across multiple disciplines and represents the gold standard for fluorescence lifetime extraction, a critical parameter that enables, for example, the discrimination of healthy and pathological tissues. Despite its demonstrated potential, the widespread deployment of TCSPC in clinically relevant and other high-impact applications has been historically prevented by a fundamental limitation: acquisition speed in classic TCSPC must be kept low to avoid pile-up distortion, thereby preventing real-time, high-throughput measurements.
HÈRMES addresses this long-standing bottleneck through four tightly integrated research directions. First, it develops a new, constraint-free TCSPC methodology, elevating a preliminarily validated concept into a comprehensive, technology-independent theoretical framework capable of redefining the TCSPC paradigm. Second, it translates this theory into practice by designing reference ultrafast electronics for next-generation systems, including smart, high-performance circuits able to sustain operation far beyond conventional pile-up-limited rates while preserving signal-to-noise ratio and linearity. Third, it conceives an innovative computational imaging framework based on the deep integration of optical design and reconstruction algorithms, enabling efficient photon collection and high-speed multi-parameter acquisition under realistic operating conditions. Fourth, it devises new architectures and tailored algorithms for managing the massive data streams generated by such high-rate systems, with the goal of demonstrating high-resolution, video-rate capabilities.
By unlocking high-speed, linear, and distortion-free TCSPC, HÈRMES is expected to expand the applicability of time-resolved imaging to critical domains such as intraoperative tumor delineation and neuronal activity analysis, where ultrafast yet reliable acquisition is essential. The anticipated impact is transformative: enabling next-generation optical imaging systems capable of supporting complex clinical and neuroscientific decision-making processes, ultimately improving surgical precision, patient outcomes, and our ability to interrogate dynamic biological phenomena in real time.
