TECH Core

U 54肿瘤免疫微环境多参数成像中心（C-MITIE） 将开发一个先进的成像和数据分析的集成工具包， 预后不良的实体瘤中免疫微环境动力学的研究。非常需要 改进的成像方法，可以促进对物理和分子机制的理解 控制天然肿瘤微环境中的免疫浸润、分布和功能。我们提出了一个 两个研究试验台的多参数成像和计算方法的数量， 有效的抗肿瘤免疫和免疫治疗的物理和分子屏障。的一大主题 TECH方法是使用无标记成像方法，可以表征和定量相互作用 免疫细胞和肿瘤微环境之间的联系。这些无标签方法主要建立在 平台方法的多光子显微镜，并可用于完整的细胞和组织模型， 扰动将使用新的荧光寿命通过代谢谱跟踪T细胞身份和活化 （FLIM）和多维成像（HDIM）方法。这些代谢敏感的方法将是 辅以全视野光学相干断层扫描（FFOCT），以揭示代谢的新见解 相关架构。基于FLIM的FRET可用于产生信号分子相互作用的新见解 与免疫微环境动力学相关将询问富含胶原的细胞外基质（ECM） 二次谐波发生（SHG）成像，用于胶原纤维拓扑测量和胶原交叉 将测量与增强后向散射光谱（EBS）相关联。多光子激发（MPE） 光化学制造可用于产生胶原纤维组织的体外细胞就绪模型， 直接基于人类数据蓝图。先进的计算分析方法，包括算法和 机器学习方法将用于检查所有多参数信号， 免疫和微环境相互作用。所有的成像和计算方法不仅将被共享， 在UW和UMN研究团队中广泛使用，但重要的是，一般癌症成像社区使用 建立硬件和开放源码软件传播协议。

This TECH core of the U54 Center for Multiparametric Imaging of Tumor Immune Microenvironments (C-MITIE) will develop an integrated toolkit of advanced imaging and data analysis to power quantitative, mechanistic investigations of immune-microenvironment dynamics in poor prognosis solid tumors. There is great need for improved imaging methods that can advance understanding of the physical and molecular mechanisms governing immune infiltration, distribution, and function in native tumor microenvironments. We propose a number of multiparametric imaging and computational methods for the two research test beds that seek to define the physical and molecular barriers to effective anti-tumor immunity and immunotherapies. A major theme of the TECH approach is to use label-free imaging approaches that can characterize and quantitate the interactions between immune cells and the tumor microenvironment. These label free methods are largely built on the platform method of multiphoton microscopy and can be used on intact cell and tissue models with minimal perturbation. T-cell identity and activation will be tracked by metabolic profiling using new fluorescence lifetime (FLIM) and hyperdimensional imaging (HDIM) approaches. These metabolically sensitive methods will be complemented by Full-Field Optical Coherence Tomography (FFOCT) to reveal new insight into metabolically relevant architecture. FLIM based FRET can be used to yield new insights into signaling molecular interactions relevant to immune-microenvironment dynamics The collagen rich extracellular matrix (ECM) will be queried with Second Harmonic Generation (SHG) imaging for collagen fiber topology measurement and collagen cross- linking measurements with Enhanced Backscattering Spectroscopy (EBS). Multiphoton Excitation (MPE) photochemistry fabrication can be used to create in vitro cell ready models of collagen fiber organization that are directly based on human data blueprints. Advanced computational analysis methods including algorithmic and machine learning approaches will be used to examine all multiparametric signals and make correlation between immune and microenvironment interactions. All imaging and computational methods will be shared not only widely within the UW and UMN research teams but importantly with the general cancer imaging community using established hardware and open source software dissemination protocols.