Optical Fluorescence and X-Ray Computed Tomography Scanner for Small Animal In-Vi

适用于小动物体内的光学荧光和 X 射线计算机断层扫描仪

• 批准号: 8262437
• 负责人: Seth D Shulman
• 金额: $ 48.74万
• 依托单位: BIOSCAN, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-16 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8262437
• 关键词: Algorithms; Anatomic Models; Anatomy; Animal Model; Animals; Area; Biological Markers; Biological Process; Biomedical Research; Cardiovascular Diseases; Cell physiology; Clinic; Communities; Computer software; Data; Databases; Development; Effectiveness; Fluorescence; Fuzzy Logic; Goals; Hemoglobin; Histocompatibility Testing; Image; Imaging Phantoms; Lasers; Lead; Learning; Life; Light; Literature; Location; Malignant Neoplasms; Maps; Measurement; Methods; Molecular; Mus; Optical Tomography; Optics; Organ; Performance; Pharmacotherapy; Phase; Preclinical Drug Evaluation; Process; Property; Relative (related person); Reporter; Research; Resolution; Roentgen Rays; Scanning; Small Animal Imaging Systems; Small Business Innovation Research Grant; Source; Staging; Surface; System; Techniques; Technology; Testing; Tissue Model; Tissues; Tomography, Computed, Scanners; Translations; X-Ray Computed Tomography; X-Ray Computed Tomography Scanners; X-Ray Tomography; aerobic respiration control protein; anticancer research; base; biological systems; design; detector; fluorescence imaging; human disease; image reconstruction; imaging Segmentation; imaging modality; improved; in vivo; instrumentation; interest; light scattering; mouse model; nanoparticle; neurological pathology; pre-clinical; prototype; public health relevance; reconstruction; research study; simulation; tissue phantom; tomography; tool; two-dimensional

DESCRIPTION (provided by applicant): The overall goal of this application is to develop a quantitative in-vivo small animal imaging system for fluorescent reporter probes that fuses fluorescence light emitting computed tomography (FLECT) with X- ray computed tomography (CT). The proposed dual-modality imaging system will not only provide a research tool for better understanding of biological function and processes on a cellular or molecular level in-vivo, but will also aid the development of new drug therapies and accelerate their translation into the clinic. Conventional imaging methods only provide two-dimensional (2D) fluorescence surface images and, hence, do not reveal the actual spatial location and concentration of the targeted reporter system. Furthermore, current fluorescence tomography (FT) systems are still in a developing stage and suffer from several limitations. First, these FT systems assume optically uniform tissue models that, consequently, prohibit the accurate quantification of the reporter probe's location and concentration. Second, neither planar fluorescence imaging nor FT provides any anatomical information. Hence, the reconstructed reporter probe location cannot be localized relative to the animal's anatomy. The proposed FLECT/CT system will overcome these limitations in two ways. First, we will leverage the anatomical information gained from CT with its high spatial resolution and assign optical properties to various segmented organs. These non-uniform optical property maps will in turn improve quantitative fluorescence image reconstruction leading to accurate images about the reporter probe's actual spatial location and concentration. Second, structural images from CT will provide the anatomical information that is necessary for co-locating the fluorescent reporter probe to the animal's anatomy. In Phase 1, we will perform numerical simulations and tissue phantom experiments that will provide a proof of principle for the proposed FLECT/CT system. We will demonstrate that (1) applying non-uniform optical property maps to FLECT reconstructions makes quantitative tomographic imaging of reporter probes feasible and (2) spatial maps of organs with largely varying optical properties can be segmented from CT images. In Phase 2, a commercial grade FLECT/CT system will be developed where the optical and X-ray components share the same rotating gantry. We will develop fully automated image segmentation methods and different techniques for assigning optical parameters to segmented organs. The optical parameters will be determined by (1) optical tomography in a reduced parameter space, (2) from known (oxy-)hemoglobin concentrations in different tissue types, or from (3) optical parameter databases of prior experiments. Last, the performance of the FLECT/CT system will be evaluated in small animal imaging experiments. Once completed, our FLECT/CT system will provide a powerful tool for research of cancer, neurological pathologies, and cardiovascular disease. PUBLIC HEALTH RELEVANCE: The proposed development of a combined fluorescence tomography and X-ray CT imaging system for small animals will reconstruct and display the three-dimensional in-vivo distribution of fluorescent reporter probes for studying molecular processes in a living biological system. The combination of fluorescence tomography with X-ray CT will significantly improve the image quality of fluorescence tomographic images and will co-register them to structural CT images showing the animal's anatomy. Therefore, the proposed imaging system would not only be of great significance for better understanding biological processes and pathological function in living small animals on a cellular and molecular level, but would also aid the development of new drug therapies and accelerate their translation into the clinic.

描述（由申请人提供）：本申请的总体目标是开发一种用于荧光报告探针的定量体内小动物成像系统，该系统融合了荧光发射计算机断层扫描（FLECT）与X射线计算机断层扫描（CT）。所提出的双模态成像系统不仅将为更好地了解体内细胞或分子水平的生物功能和过程提供研究工具，而且还将有助于新药物疗法的开发并加速其转化为临床。传统的成像方法仅提供二维 (2D) 荧光表面图像，因此无法揭示目标报告系统的实际空间位置和浓度。此外，当前的荧光断层扫描（FT）系统仍处于发展阶段，并存在一些局限性。首先，这些 FT 系统假定光学均匀的组织模型，因此无法准确量化报告探针的位置和浓度。其次，平面荧光成像和 FT 都不提供任何解剖信息。因此，重建的报告探针位置不能相对于动物的解剖结构进行定位。所提出的 FLECT/CT 系统将以两种方式克服这些限制。首先，我们将利用从 CT 获得的高空间分辨率的解剖信息，并将光学属性分配给各个分割的器官。这些不均匀的光学特性图反过来将改善定量荧光图像重建，从而获得有关报告探针的实际空间位置和浓度的准确图像。其次，CT 的结构图像将提供将荧光报告探针与动物解剖结构共同定位所需的解剖信息。在第一阶段，我们将进行数值模拟和组织模型实验，为拟议的 FLECT/CT 系统提供原理证明。我们将证明（1）将非均匀光学特性图应用于 FLECT 重建使得报告探针的定量断层成像变得可行，（2）可以从 CT 图像中分割出光学特性变化很大的器官的空间图。在第二阶段，将开发商业级 FLECT/CT 系统，其中光学和 X 射线组件共享相同的旋转机架。我们将开发全自动图像分割方法和不同的技术来为分割的器官分配光学参数。光学参数将通过以下方式确定：(1) 缩小参数空间中的光学断层扫描，(2) 根据不同组织类型中已知的（氧合）血红蛋白浓度，或根据 (3) 先前实验的光学参数数据库。最后，FLECT/CT系统的性能将在小动物成像实验中进行评估。一旦完成，我们的 FLECT/CT 系统将为癌症、神经病理学和心血管疾病的研究提供强大的工具。 公共健康相关性：拟议开发的用于小动物的荧光断层扫描和 X 射线 CT 成像组合系统将重建和显示荧光报告探针的三维体内分布，用于研究活体生物系统中的分子过程。荧光断层扫描与 X 射线 CT 的结合将显着提高荧光断层扫描图像的图像质量，并将其与显示动物解剖结构的结构 CT 图像共同配准。因此，所提出的成像系统不仅对于在细胞和分子水平上更好地了解活体小动物的生物过程和病理功能具有重要意义，而且还有助于新药物疗法的开发并加速其转化为临床。