3D Time Domain Molecular Imaging

3D 时域分子成像

• 批准号: 6791256
• 负责人: VASILIS NTZIACHRISTOS
• 金额: $ 38.84万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791256
• 关键词: atherosclerosis; bioimaging /biomedical imaging; biomarker; breast neoplasms; disease /disorder model; enzyme activity; fluorescent dye /probe; gene targeting; genetically modified animals; imaging /visualization /scanning; immunocytochemistry; laboratory mouse; magnetic resonance imaging; neoplastic growth; rheumatoid arthritis; technology /technique development; tomography

DESCRIPTION (provided by applicant): The recent emergence of novel molecular fluorescent probes and proteins has enabled the in-vivo interrogation of molecular function and significantly enhanced our ability to study pathogenesis in vivo. While advances in fluorochrome probe development have been rapid, the corresponding technologies for in-vivo imaging have been largely limited to qualitative photographic approaches of close to the surface events (reflectance imaging). In order to image molecular events deeper in tissue, we have recently developed a prototype scanner for fluorescence-mediated molecular tomography (FMT) of small animals and imaging of molecular targets. Major challenges that remain in vivo are a) to improve resolution, b) to quantitatively image the full-body distribution of specific molecular markers and c) to merge molecular reconstructions with high-resolution surface features for high positional accuracy rendering. In this proposal we seek to develop a highly optimized imaging system with unprecedented three-dimensional detection capacity. In particular we propose the use of a time-gated intensified CCD camera for high spatial and temporal sampling of fluorescent signals and combine it with non-contact detection geometries, concurrent reflectance imaging and high-resolution three-dimensional boundary extraction. Furthermore, we aim at developing fast reconstruction schemes, appropriate for the large data-sets acquired and for non-contact geometries, in order to resolve and quantify fluorochrome concentration, activation and fluorescence lifetime. FMT is one of the few truly enabling technologies for molecular imaging since it capitalizes on signal amplification and fluorescence activation (molecular switches or beacons), high detection sensitivity and chemical specificity. Furthermore, it uses stable reporters, non-ionizing radiation and can simultaneously image multiple targets by spectral differentiation. Recent studies have also shown the potential of using this technology to interrogate human tissues. FMT is expected to enhance our ability to study molecular pathways, perform early detection of disease, real time molecular medicine and ultimately patient-tailored treatment.

描述（由申请人提供）： 最近出现的新型分子荧光探针和蛋白质使得体内分子功能的研究成为可能，并显着增强了我们研究体内发病机制的能力。虽然荧光染料探针的开发进展迅速，但体内成像的相应技术在很大程度上仅限于接近表面事件的定性摄影方法（反射成像）。为了对组织更深处的分子事件进行成像，我们最近开发了一种原型扫描仪，用于小动物的荧光介导分子断层扫描（FMT）和分子目标成像。体内仍然存在的主要挑战是a）提高分辨率，b）对特定分子标记的全身分布进行定量成像，以及c）将分子重建与高分辨率表面特征融合以实现高位置精度渲染。在本提案中，我们寻求开发一种高度优化的成像系统，具有前所未有的三维检测能力。我们特别建议使用时间选通增强型 CCD 相机对荧光信号进行高空间和时间采样，并将其与非接触式检测几何结构、并发反射成像和高分辨率三维边界提取相结合。此外，我们的目标是开发快速重建方案，适用于获取的大型数据集和非接触几何形状，以便解析和量化荧光染料浓度、激活和荧光寿命。 FMT 是为数不多的真正支持分子成像的技术之一，因为它利用了信号放大和荧光激活（分子开关或信标）、高检测灵敏度和化学特异性。此外，它使用稳定的报告基因、非电离辐射，并且可以通过光谱区分同时对多个目标进行成像。最近的研究还表明了使用该技术来研究人体组织的潜力。 FMT 有望增强我们研究分子途径、进行疾病早期检测、实时分子医学以及最终为患者量身定制治疗的能力。