PROJECT SUMMARY – Technology Research and Development Project #1 The objective of TRD 1 is to technologically advance and integrate interventional fluorescence lifetime imaging (iFLIM) technology in clinical settings for real-time in-situ tissue diagnosis and guidance of surgical procedures. While the basic principles of FLIM technology are well-established and FLIM-based techniques are used extensively in cell culture microscopy and small-animal imaging, FLIM’s complex instrumentation and engineering difficulties for compact clinical fiber probes, long data acquisition times, and complex data analysis present significant barriers to its wide dissemination and limits its clinical adoption. TRD 1 joins the unique expertise in iFLIM at UC Davis with expertise in detector technologies, photonic integration, micro-endoscopy, and optical imaging to address current technological barriers, advance fundamental FLIM technology, and achieve greater clinically utility. TRD 1 consists of four Specific Aims: Aim 1 will improve iFLIM performance through the advancement of hyperspectral detector array built with monolithically integrated encoder patterns. New iFLIM detector technology with significantly improved sensitivity (10-fold) and speed (5-to-10-fold enhancement) compared to current technology and ability to perform fast multispectral measurements will be created. Aim 2 will expand iFLIM clinical utility by building devices capable of real-time, highly specific, quantitative imaging. Scalable miniaturized iFLIM systems that integrate planar imaging devices (spectrometer- on-a-chip) with high-speed readout integrated electronics (ROIC) based on innovative packaging strategies will be generated. Aim 3 will link iFLIM with other optical imaging devices. We will develop interfacing components based on advanced fiber optic and micro-endoscopic technology to enable multimodal imaging and access to internal organs. iFLIM compatible catheter technologies enabling coupling of iFLIM with other optical modalities (e.g., OCT, iDOS) permit simultaneous evaluation of complementary tissue signatures and expansion of iFLIM indications from open-field surgery to stereotactic biopsy, endovascular techniques and other minimally invasive interventions. Aim 4 will incorporate iFLIM into surgical guidance. We will develop strategies to integrate iFLIM into procedural workflow. Methodologies for standardization and effective integration of iFLIM devices in a clinically viable workflow will be generated. Impact: This TRD will create innovative, scalable iFLIM technology for intraprocedural use and generate prototypes and intraprocedural methodologies/protocols enabling wide dissemination of iFLIM devices, including through CPs and SPs, to promote their broader adoption. The acquired FLIm parameter database/cluster will enable subsequent multi-center clinical trials for automated tissue classification and diagnostic prediction. Although the initial clinical focus of this TRD is ...