TRD1: Interventional Fluorescence Lifetime Imaging Microscopy (iFLIM)

项目概要-技术研究与开发项目#1 TRD 1的目标是在技术上推进和整合介入荧光寿命成像 （iFLIM）技术在临床环境中用于实时原位组织诊断和外科手术指导。 虽然FLIM技术的基本原理已经很好地建立，并且使用基于FLIM的技术 FLIM在细胞培养显微镜和小动物成像方面有着广泛的应用， 紧凑型临床光纤探头、长数据采集时间和复杂数据分析的工程困难 对它的广泛传播存在重大障碍，并限制了它的临床应用。TRD 1加入了独特的 在加州大学戴维斯分校的iFLIM专业知识，在探测器技术，光子集成，显微内窥镜， 和光学成像，以解决当前的技术障碍，推进基本FLIM技术， 实现更大的临床效用。TRD 1包括四个具体目标：目标1将提高iFLIM性能 通过用单片集成编码器图案构建的高光谱探测器阵列的进步。 新的iFLIM检测器技术，灵敏度（10倍）和速度（5至10倍）显著提高 增强）与当前技术相比，执行快速多光谱测量的能力将 创造Aim 2将通过构建能够实时、高度特异性 定量成像集成了平面成像设备（光谱仪）的可扩展小型化iFLIM系统 基于创新封装策略的高速读出集成电子器件（ROIC）将 生成。Aim 3将把iFLIM与其他光学成像设备连接起来。我们将开发接口组件 基于先进的光纤和显微内窥镜技术，实现多模式成像， 内脏iFLIM兼容导管技术可实现iFLIM与其他光学模态的耦合 (e.g., OCT、iDOS）允许同时评价互补组织特征和iFLIM扩张 适应症从开放野手术到立体定向活检、血管内技术和其他微创 干预措施。Aim 4将iFLIM纳入手术指导。我们将制定整合iFLIM的战略 进入程序流程。用于标准化和有效集成iFLIM设备的方法， 将生成临床可行的工作流程。影响：该TRD将创建创新的、可扩展的iFLIM技术 供术中使用，并生成原型和术中方法/方案， 通过CP和SP等方式传播iFLIM设备，以促进其更广泛的采用。所获取的 FLIm参数数据库/集群将支持后续的自动组织多中心临床试验 分类和诊断预测。尽管本TRD的初始临床重点是外科肿瘤学， 先进的iFLIM应该证明在其它过程中是有用的（例如，心血管、神经系统疾病、器官/组织 移植）。

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 surgical oncology, advanced iFLIM should prove useful in other procedures (e.g., cardiovascular, neurologic disease, organ/tissue transplantation).