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

总结 PhotoSound Technologies公司建议开发一种新型成像模式来进行表征和预处理 小鼠模型的临床研究。该技术将能够实现三维功能， 荧光标记和报告基因的分子成像，在强大的解剖结构上以高保真度映射 组织，例如皮肤、中央和外周脉管系统和内部器官。开发的仪器 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）在生物医学领域非常受欢迎。 研究人员将其作为经济实惠、方便且非常灵敏的分子成像工具用于临床前研究， 建立动物模型。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。一种高分辨率活体3D成像方法， 它可以很容易地与光学成像集成在一个单一的仪器，将有很大的影响， 整个小动物研究领域。 光声层析成像是一种新兴的生物医学成像模式，具有以下所有要求：（1） 3D全身图像的分辨率为150-500 µm;（2）能够使用相同的仪器激发 荧光和光声效应的产生;（3）在不到1分钟内进行3D扫描。然而，在体内 与常规荧光技术相比，检测荧光团的灵敏度较差。我们的建议 是基于开创性的共同注册的整合荧光和光声模态在一个单一的 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 用于在单个紧凑型中共同配准3D光声层析成像和荧光的实现 （2）对小鼠的荧光团和解剖结构进行成像， 分辨率超过已建立的荧光成像的分辨率;（3）提供有价值的成像信息， 临床前动物模型的开发和表征，病例研究重点是小鼠模型， 转移性乳腺癌 第二阶段将集中于开发和体内验证一种具有灵敏度和 针对动物模型开发和临床前研究的各个领域进行了优化的成像程序。 最终的商业系统将能够在体内可视化和分析天然血红蛋白，荧光团， 纳米颗粒和其他用于跟踪、绘图和纵向研究的光敏结构。的 PAFT-3D的价值主张将不仅建立在独特性和技术优势的基础上， 产品，但也通过使其负担得起的广泛人口的研究小组和中心。

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.