Whole body tomography of fluorescent proteins in vivo

体内荧光蛋白的全身断层扫描

• 批准号: 7488838
• 负责人: VASILIS NTZIACHRISTOS
• 金额: $ 31.07万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7488838
• 关键词: Animals; Arts; Biological; Biological Monitoring; Biological Process; Biology; Cells; Characteristics; Color; Controlled Environment; Dependence; Depth; Detection; Development; Drug Evaluation; Fluorescence; Goals; Heterogeneity; Image; Imagery; Immune; In Vitro; Knowledge; Laboratories; Lead; Lighting; Measurement; Methods; Microscopy; Optical Tomography; Optics; Penetration; Performance; Photons; Property; Proteins; Proteomics; Reporter; Research; Research Personnel; Resolution; Roentgen Rays; Scanning; Scheme; Skin; Small Animal Imaging Systems; Source; Specificity; Stem cells; Surface; System; Techniques; Technology; Testing; Theoretical model; Three-Dimensional Image; Tissues; Weight; attenuation; base; design; functional genomics; improved; in vivo; millimeter; multi-photon; novel; programs; protein expression; protein function; reconstruction; tomography; trafficking

DESCRIPTION (provided by applicant): Fluorescent Proteins (FP) have become essential reporter molecules for the elucidation of the function of proteins within cells, the bio-distribution of immune and stem cells and for evaluation of drug candidates in vivo. Volumetric detection and accurate quantification of Fluorescent Proteins in entire animals would greatly enhance our ability to monitor biological processes in vivo. Currently however, whole body fluorescent protein imaging is largely facilitated by photographic techniques that compromise the quantification and any volumetric imaging ability. The overall goal of this proposal is therefore to develop whole body, quantitative Fluorescence Protein Tomography (FPT) in entire animals. This development necessitates 1) the use of novel scanning technologies, 2) the advancement of theoretical models of photon propagation appropriate for imaging in the visible and far-red, 3) the design of computationally efficient inversion techniques with multispectral characteristics and 4) the interrogation of appropriate fluorescent proteins that can yield high detection sensitivity. Of particular importance for achieving high imaging performance is the utilization of freespace 360 degree projection tomographic principles and appropriate auto-fluorescent subtraction schemes that lead to unprecedented imaging performance compared to the current state of the art. Overall we hypothesize that the imaging accuracy imparted by FPT, combined with the high specificity and versatility achieved by fluorescent protein reporters and the high detection sensitivity afforded by novel red-shifted constructs can revolutionize biological imaging and propagate FPT as the method of choice in the biological laboratory for volumetric whole animal imaging.

描述（由申请人提供）：荧光蛋白（FP）已成为阐明细胞内蛋白质功能，免疫和干细胞的生物分布以及在体内评估候选药物的必不可少的报告分子。整个动物中荧光蛋白的体积检测和准确定量将大大增强我们在体内监测生物过程的能力。但是，目前，全身荧光蛋白成像在很大程度上是通过损害定量和任何体积成像能力的照相技术来促进的。因此，该提案的总体目标是在整个动物中发展全身，定量荧光蛋白断层扫描（FPT）。这种发展需要1）使用新颖的扫描技术，2）适用于可见且远红色中成像的光子传播的理论模型的发展，3）3）具有多光谱特征的计算有效反转技术的设计，以及4）4）对适当的荧光蛋白的质疑，可以产生高检测的敏感性。对于获得高成像性能，至关重要的是FreeSpace 360​​度投影层造影原理和适当的自动荧光减法方案的利用，这与当前的艺术状态相比导致了前所未有的成像性能。总体而言，我们假设FPT赋予的成像精度，再加上荧光蛋白报道器所获得的高特异性和多功能性以及新型红移构建体提供的高检测敏感性可以彻底改变生物学成像，并传播FPT，作为大量全动物的生物实验室中选择的方法。