3D Time Domain Molecular Imaging

3D 时域分子成像

• 批准号: 6659790
• 负责人: VASILIS NTZIACHRISTOS
• 金额: $ 37.38万
• 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/6659790
• 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）： 最近出现的新的分子荧光探针和蛋白质，使在体内的分子功能的询问，并显着提高了我们的能力，在体内研究发病机制。虽然荧光染料探针的开发进展迅速，但用于体内成像的相应技术在很大程度上限于接近表面事件的定性摄影方法（反射成像）。为了成像分子事件更深的组织，我们最近开发了一种原型扫描仪的荧光介导的分子断层扫描（FMT）的小动物和成像的分子目标。在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合并以进行高位置精度绘制。在这项提案中，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。特别是，我们建议使用的时间选通增强CCD相机的高空间和时间采样的荧光信号和联合收割机结合它与非接触式检测几何形状，并发反射成像和高分辨率的三维边界提取。此外，我们的目标是开发快速重建方案，适用于采集的大型数据集和非接触几何形状，以解决和量化荧光染料浓度，激活和荧光寿命。FMT是为数不多的真正能够实现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，它使用稳定的报告分子，非电离辐射，并可以通过光谱微分同时成像多个目标。最近的研究也显示了使用这种技术来询问人体组织的潜力。FMT有望提高我们研究分子通路的能力，进行疾病的早期检测，真实的时间分子医学和最终为患者量身定制的治疗。