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

• 批准号: 9201342
• 负责人: Sergey A Ermilov
• 金额: $ 21.15万
• 依托单位: PHOTOSOUND TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9201342
• 关键词: Address; Anatomy; Animal Experimentation; Animal Model; Area; Biological; Biology; Bioluminescence; Biomedical Research; Blood Vessels; Breast Cancer Model; Carbon nanoparticle; Cardiovascular system; Case Study; Code; Data; Detection; Development; Developmental Biology; Devices; Dimensions; Engineering; Fluorescence; Functional Imaging; Generations; Gold; Hemoglobin; Image; Imagery; Imaging Device; Imaging Techniques; Imaging technology; Individual; Inferior; Kidney; Label; Light; Lipids; Longitudinal Studies; Malignant Neoplasms; Maps; Measurement; Medicine; Melanins; Metastatic breast cancer; Methodology; Modality; Modeling; Molecular; Mus; Neoplasm Metastasis; Optical Methods; Organ; Outcome; Peripheral; Phase; Photosensitivity; Population Research; Procedures; Process; Quantum Dots; Reporter Genes; Research; Research Personnel; Resolution; Rodent Model; Scanning; Sentinel Lymph Node; Skin; Small Business Innovation Research Grant; Spleen; Structure; System; Techniques; Technology; Testing; Three-Dimensional Image; Three-Dimensional Imaging; Tissue Engineering; Toxicology; Trees; Ultrasonography; Validation; Water; anatomic imaging; animal model development; base; bioimaging; cancer cell; chromophore; clinical development; commercialization; cost; data acquisition; design; experience; fluorescence imaging; fluorophore; graphical user interface; high resolution imaging; human disease; imaging approach; imaging modality; imaging system; in vivo; in vivo imaging; in vivo optical imaging; innovation; instrument; instrumentation; molecular imaging; mouse model; nanoparticle; novel; optical imaging; optoacoustic tomography; photoacoustic imaging; plasmonics; pre-clinical; pre-clinical research; preclinical study; prototype; reconstruction; research and development; tissue regeneration; two-dimensional; whole body imaging

SUMMARY PhotoSound Technologies, Inc. proposes to develop a novel imaging modality for characterization and pre- clinical research of murine 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 developed instrument could be used in broad spectrum of pre-clinical research including cancer, toxicology, tissue engineering and regeneration, cardiovascular and developmental biology. Optical in vivo imaging methods (fluorescence and bioluminescence) found great popularity among researchers as affordable, convenient, and very sensitive molecular imaging tools for pre-clinical 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 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 biomedical imaging modality that has all those requirements: (1) 150-500 µm resolution of 3D whole body images; (2) Ability to use the same instrumentation for excitation of fluorescence and generation of photoacoustic effect; (3) 3D scans in less than 1 minute. However, its in vivo sensitivity to detection of fluorophores is inferior as compared to regular fluorescence techniques. Our proposal is based on pioneering co-registered integration of fluorescence and photoacoustic modalities in a single compact 3D configuration (PAFT-3D) defeating shortcomings of each individual technology. The Phase I project is organized in three specific aims assessing feasibility of: (1) Technological implementation for co-registered 3D photoacoustic tomography and fluorescence in a single compact instrument for imaging live anesthetized mice; (2) Imaging fluorophores and anatomical structures of mice with resolution exceeding that of established fluorescence imaging; (3) Providing imaging information valuable for development and characterization of pre-clinical animal models with case study focused on murine models of metastatic breast cancer. Phase II will be focused on development and in vivo validation of a commercial instrument with sensitivity and imaging procedures optimized for various areas of animal model development and preclinical research. Ultimate commercial system will enable in vivo visualization and analysis of native hemoglobin, fluorophores, nanoparticles, and other photosensitive constructs used for tracking, mapping, and longitudinal studies. The value proposition of the PAFT-3D will be built not only around uniqueness and technological superiority of the product, but also by making it affordable for a broad population of research groups and centers.

概括 PhotoSound Technologies, Inc. 提议开发一种新颖的成像模式，用于表征和预成像 小鼠模型的临床研究。该技术将能够实现三维功能和 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，例如皮肤、中枢和外周脉管系统以及内脏器官。研制的仪器 可用于广泛的临床前研究，包括癌症、毒理学、组织工程和 再生、心血管和发育生物学。 光学体内成像方法（荧光和生物发光）在人们中广受欢迎 为研究人员提供负担得起、方便且非常灵敏的分子成像工具，用于临床前研究和 动物模型的开发。然而，它们的独立应用受到空间分辨率差的阻碍 以及图像的二维性所施加的限制。高分辨率体内3D成像方法， 它可以很容易地与光学成像集成在一台仪器中，这将对 小动物研究的整个领域。 光声断层扫描是一种新兴的生物医学成像方式，具有所有这些要求：(1) 150-500 µm分辨率的3D全身图像； (2) 能够使用相同的仪器进行激励 荧光和光声效应的产生； (3) 3D 扫描时间不到 1 分钟。然而，其在体内 与常规荧光技术相比，荧光团检测的灵敏度较差。我们的建议 基于开创性地将荧光和光声模式共同注册集成在一个单一的 紧凑的 3D 配置 (PAFT-3D) 克服了每种技术的缺点。 第一阶段项目分为三个具体目标，评估以下方面的可行性：(1) 技术 在单个紧凑型器件中实现联合配准 3D 光声断层扫描和荧光 对活体麻醉小鼠进行成像的仪器； (2) 小鼠荧光团和解剖结构成像 分辨率超过已建立的荧光成像； (3) 提供有价值的影像信息 临床前动物模型的开发和表征，重点关注小鼠模型的案例研究 转移性乳腺癌。 第二阶段将侧重于开发和体内验证具有灵敏度和性能的商业仪器 针对动物模型开发和临床前研究的各个领域优化的成像程序。 最终的商业系统将能够对天然血红蛋白、荧光团、 纳米粒子和其他用于跟踪、绘图和纵向研究的光敏结构。这 PAFT-3D 的价值主张不仅建立在其独特性和技术优势之上 产品，而且还使广大研究团体和中心能够负担得起。