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In-vivo optical molecular imaging with Dynamic Contrast Enhancement (DyCE)

动态对比度增强 (DyCE) 体内光学分子成像

基本信息

批准号：
7485551
负责人：
RICHARD M. LEVENSON
金额：
$ 16.75万
依托单位：
CAMBRIDGE RESEARCH AND INSTRUMENTATION
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7485551
关键词：
Address Adoption Algorithms Anatomy Animals Automatic Data Processing Back Basic Science Body Surface Bolus Infusion Characteristics Classification Collaborations Complex Computer software Contrast Media Data Data Display Depth Detection Development Disease Disease model Drug Kinetics Dyes Fluorescence General Hospitals Image Image Analysis Imagery Imaging Device Imaging Techniques Individual Indocyanine Green Injection of therapeutic agent Kinetics Label Legal patent Location Machine Learning Magnetic Resonance Maps Massachusetts Measurement Medical Imaging Methods Modality Modeling Modification Molecular Molecular Probes Mus Nature Optics Organ Paper Performance Physiological Positioning Attribute Protocols documentation Purpose Range Research Research Personnel Retrieval Series Signal Transduction Small Animal Imaging Systems Software Tools Solutions Source Structure Surface System Techniques Technology Testing Time Time Series Analysis Tissues Validation Variant Virginia Visualization software X-Ray Computed Tomography Xenograft procedure absorption base blind data acquisition drug development drug discovery experience hemodynamics image reconstruction improved in vivo instrumentation light scattering longitudinal animal study millimeter molecular imaging novel strategies optical imaging photonics prototype response spatiotemporal subcutaneous tumor

项目摘要

DESCRIPTION (provided by applicant): Fluorescence-based molecular Imaging in small animals is having a major impact on drug development and disease research. However, a significant challenge to imaging targeted fluorescent markers in vivo remains: unless the labeled regions are located superficially; localization, quantitation and host organ identification are impeded by the effects of light scattering and absorption. Orthotopic tumor and disease models are increasingly preferred over less biologically relevant subcutaneous xenografts. In such studies, substantial difficulties are encountered in longitudinal studies where animals are growing and are positioned differently for each measurement. We believe that a single imaging advance could address many of these issues, and advance the utility of in-vivo molecular imaging: an exact anatomical co-registration technique that does not rely on multimodal techniques. This proposal describes dynamic molecular imaging (DMI), an approach that can provide co-registered anatomical information by exploiting in-vivo pharmacokinetics of dyes in small animals in a simple and inexpensive way. We demonstrate that by acquiring a time-series of optical images during injection of an inert dye, we can repeatably and accurately delineate the major internal organs of mice using optical imaging alone. This is possible because each major organ is "illuminated" by the kinetics of dye passing through it in such a manner as to make it distinguishable from other structures. Spatiotemporal analysis can exploit these characteristic time courses to allow the body-surface representation of each organ to be visualized. These in- vivo anatomical maps can be overlaid onto simultaneously acquired images of a targeted molecular probe (detected and distinguished from the mapping dye via multispectral imaging techniques, if necessary) to significantly aid in identification of the probe's anatomical and physical location. Using CRi's existing and prototype 2D, "2.5D" and true 3D multispectral mouse imaging systems, we propose to test and refine a DMI approach. Based on our findings to date, we will examine and exploit in-vivo pharmacokinetics of the near-infrared dye, indocyanine green, to generate delineated surface projections of individual organs. Co-registering this surface map with surface projections of detected targeted labels will allow the targeted probe's 3D spatial location to be inferred. This information can further be used to improve quantitative accuracy in longitudinal molecular imaging studies of deep targets.

描述（由申请人提供）：小动物荧光分子成像对药物开发和疾病研究有重大影响。然而，在体内对靶向荧光标记物成像仍然存在一个重大挑战：除非标记区域位于表面；光散射和吸收的影响阻碍了定位、定量和宿主器官的识别。原位肿瘤和疾病模型越来越多地优先于较少生物学相关性的皮下异种移植物。在这些研究中，纵向研究遇到了很大的困难，因为动物正在生长，每次测量的位置都不同。我们相信单个成像的进步可以解决许多这些问题，并推进体内分子成像的实用性：一种不依赖于多模态技术的精确解剖共配技术。动态分子成像（dynamic molecular imaging， DMI）是一种通过利用染料在小动物体内的药代动力学，以一种简单而廉价的方式提供共同注册解剖信息的方法。我们证明，通过在注射惰性染料期间获得光学图像的时间序列，我们可以重复和准确地描绘小鼠的主要内脏器官，仅使用光学成像。这是可能的，因为每个主要器官都被通过它的染料动力学“照亮”，从而使其与其他结构区分开来。时空分析可以利用这些特征时间过程，使每个器官的体表表现可视化。这些体内解剖图谱可以叠加到同时获得的目标分子探针的图像上（如果需要，可以通过多光谱成像技术检测并与定位染料区分），以显著帮助识别探针的解剖和物理位置。利用CRi现有的2D、“2.5D”和真正的3D多光谱小鼠成像系统和原型，我们建议测试和完善DMI方法。基于我们到目前为止的发现，我们将研究和利用近红外染料吲哚菁绿的体内药代动力学，以产生单个器官的表面投影。将该表面地图与检测到的目标标签的表面投影共同注册，将允许推断目标探针的3D空间位置。这些信息可以进一步用于提高深层目标纵向分子成像研究的定量准确性。