TRD1: Interventional Fluorescence Lifetime Imaging Microscopy (iFLIM)

项目总结-技术研究和开发项目#1 TRD1的目标是在技术上改进和集成介入性荧光寿命成像 (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确立，并且使用了基于Flim的技术 在细胞培养显微镜和小动物成像方面，弗利姆的复杂仪器和 紧凑型临床光纤探头的工程困难、数据采集时间长和复杂的数据分析 给它的广泛传播带来了重大障碍，并限制了它的临床应用。TRD 1加入独一无二的 加州大学戴维斯分校的iFLIM专业知识，包括探测器技术、光子集成、显微内窥镜、 和光学成像，以解决当前的技术障碍，推进基本胶片技术，以及 实现更大的临床实用价值。TRD1由四个具体目标组成：目标1将提高iFLIM的性能 通过利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探测器技术具有显著提高的灵敏度(10倍)和速度(5至10倍 增强)相比当前技术和执行快速多光谱测量的能力将是 已创建。AIM 2将通过构建能够实时、高度特异性 定量成像。可扩展的小型化iFLIM系统，集成了平面成像设备(光谱仪- 片上)和基于创新封装策略的高速读出集成电路(ROIC)将 将被生成。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，实现多模式成像和访问 内脏。IFLIM兼容导管技术，可实现iFLIM与其他光学模式的耦合 (例如，OCT、IDOS)允许同时评估互补组织签名和iFLIM的扩展 从开野手术到立体定向活检、血管内技术和其他微创技术的适应症 干预措施。AIM 4将把iFLIM纳入手术指导。我们将制定整合iFLIM的策略 转化为程序性工作流程。IFLIM设备的标准化和有效集成方法 临床上可行的工作流程将被生成。影响：此TRD将创建创新、可扩展的iFLIM技术 以供程序内使用，并生成原型和程序内方法/协议，从而实现广泛的 传播iFLIM设备，包括通过CPS和SP，以促进其更广泛的采用。被收购的 Flim参数数据库/集群将支持自动化组织的后续多中心临床试验 分类和诊断预测。虽然TRD最初的临床重点是外科肿瘤学， 先进的iFLIM应该在其他程序中被证明是有用的(例如，心血管、神经疾病、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).