Integrated photoacoustic and fluorescence imaging system for anatomical, functional, and molecular characterization of murine models

集成光声和荧光成像系统，用于小鼠模型的解剖、功能和分子表征

基本信息

批准号：
10680593
负责人：
Sergey A Ermilov
金额：
$ 92.68万
依托单位：
PHOTOSOUND TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10680593
关键词：
3-Dimensional Algorithms Anatomy Animal Experimentation Animal Model Animals Area Biological Markers Bioluminescence Biomedical Research Blood Cardiovascular system Characteristics Chromosome Mapping Collaborations Compensation Computer software Contrast Media Cost Savings Data Data Analyses Dedications Detection Development Developmental Biology Drainage procedure Drug Costs Electronics Engineering Environment Feedback Fluorescence Functional Imaging Funding Future Generations Head Hemoglobin Housing Illinois Image Imaging Device Imaging Techniques Individual Injections Label Laboratory Animal Production and Facilities Legal patent Longitudinal Studies Magnetic Resonance Imaging Malignant Neoplasms Maps Metastatic breast cancer Methods Modality Modeling Molecular Multimodal Imaging Neoplasm Metastasis Neurosciences Nude Mice Optics Organ Outcome Performance Peripheral Phase Positron-Emission Tomography Production Rattus Reporter Genes Research Research Contracts Research Personnel Resolution Resources Robotics Rodent Model Scanning Signal Transduction Skin Small Business Innovation Research Grant Source Spatial Distribution Specimen Handling Spinal Cord System Tail Technology Testing Therapeutic Three-Dimensional Imaging Three-dimensional analysis Time Tissue Engineering Toxicology Universities Validation Washington Work anatomic imaging animal facility animal imaging animal model development arm clinically significant data acquisition data visualization deep learning design drug development drug discovery experience field study fluorescence imaging fluorophore human disease human model image reconstruction imaging facilities imaging modality imaging platform imaging system improved in vivo in vivo imaging in vivo imaging system in vivo optical imaging instrument lymph nodes meter molecular imaging mouse model multimodality nanoparticle novel optical imaging optoacoustic tomography photoacoustic imaging pre-clinical pre-clinical research preclinical development preclinical study prototype reconstruction regenerative biology research and development single photon emission computed tomography spinal cord regeneration stem cell self renewal stem cells subcutaneous success three-dimensional visualization tissue regeneration tomography two-dimensional ultrasound whole body imaging

项目摘要

SUMMARY PhotoSound Technologies, Inc. proposes to develop a novel imaging modality for characterization and preclinical research of small animal models. The technology will be capable of three-dimensional functional and molecular imaging of fluorescent labels and reporter genes mapped with high fidelity over robust anatomical structures, such as skin, central and peripheral vasculature, and internal organs. The Phase II commercial instrument is designed to perform high-throughput whole body imaging of rodent models. It could be used in broad spectrum of preclinical research applications including cancer, toxicology, tissue engineering and regeneration, cardiovascular and developmental biology. In addition to qualitatively superior performance characteristics, the proposed multimodality imaging platform will significantly reduce space and funds required to house and operate a whole-body imaging platform at an animal research facility. Optical in vivo imaging methods (fluorescence and bioluminescence) found great popularity among researchers as affordable, convenient, and very sensitive molecular imaging tools for preclinical studies and development of animal models. However, their stand-alone application is impeded by poor spatial resolution and limitations imposed by two-dimensionality of the images. A fast and high-resolution in vivo 3D imaging method, which could be easily integrated with optical imaging in a single instrument, would have a great impact on the entire field of small animal research. Photoacoustic tomography is an emerging whole body 3D imaging modality capable of 200-500 µm resolution. It can also use the same components for excitation of fluorescence and generation of photoacoustic effect. However, its in vivo application for detection of fluorophores is impeded by strong background generated by native blood. Also, there are no commercial or research photoacoustic whole- body imaging instrument that could work with high-throughput imaging procedures (<5 min per animal). Our proposal shows a way to defeat shortcomings of each individual technology and enable fast high-resolution whole body 3D imaging of fluorescent biomarkers by integrating robotic scanning and multi-view orthogonal fluorescence and photoacoustics in a single co-registered modality (PAFT). The Phase II project is focused on development of a commercial PAFT instrument and is organized in three specific aims: (1) Develop, fabricate, and assess the performance of a commercial PAFT instrument; (2) Develop and implement high-throughput PAFT image reconstruction method; (3) Field-test the commercial PAFT instrument. Ultimate commercial system will enable high-throughput in vivo 3D visualization and analysis of native hemoglobin, fluorophores, nanoparticles, and other photosensitive constructs used for molecular and functional mapping and longitudinal studies. Such an instrument would alleviate subjective interpretation of missing and misregistered imaging data and would streamline the preclinical phase of development, leading to a higher success rate and lower costs of drug development.

概括 PhotoSound Technologies, Inc. 提议开发一种新颖的成像方式来表征和该技术将能够进行小动物模型的临床前研究。荧光标记和报告基因的分子成像在稳健的解剖学上以高保真度绘制结构，如皮肤、中枢和外周脉管系统以及内脏器官。该仪器旨在对啮齿动物模型进行高通量全身成像。广泛的临床前研究应用，包括癌症、毒理学、组织工程和除了质量上优越的性能外，再生、心血管和发育生物学。特点，拟议的多模态成像平台将显着减少所需的空间和资金在动物研究设施中安置和操作全身成像平台。光学体内成像方法（荧光和生物发光）在研究人员中广受欢迎作为用于临床前研究和开发的经济实惠、方便且非常灵敏的分子成像工具然而，它们的独立应用受到空间分辨率差和局限性的阻碍。一种快速、高分辨率的体内 3D 成像方法。可以轻松地将光学成像集成在一台仪器中，将对整个仪器产生巨大影响光声断层扫描是一种新兴的全身 3D 成像方式。它还可以使用相同的组件进行荧光激发和分辨率为 200-500 µm。然而，其在体内检测荧光团的应用受到阻碍。此外，还没有商业或研究的光声整体。我们的身体成像仪器可用于高通量成像程序（每只动物 <5 分钟）。该提案展示了一种克服每种技术的缺点并实现快速高分辨率的方法通过集成机器人扫描和多视图正交对荧光生物标记物进行全身 3D 成像单一联合配准模态 (PAFT) 中的荧光和光声。第二阶段项目的重点是开发商业 PAFT 仪器，分为三个阶段具体目标： (1) 开发、制造并评估商业 PAFT 仪器的性能； (2) 开发并实现高通量PAFT图像重建方法；（3）对商业PAFT进行现场测试；最终的商业系统将实现体内 3D 可视化和分析的高通量。天然血红蛋白、荧光团、纳米粒子和其他用于分子和这样的工具将减轻对功能的主观解释。缺失和错误配准的成像数据，将简化临床前开发阶段，从而导致更高的成功率和更低的药物开发成本。