Optical Molecular Tomography for Regenerative Medicine

用于再生医学的光学分子断层扫描

基本信息

批准号：
8678528
负责人：
SHAY SOKER
金额：
$ 69.17万
依托单位：
RENSSELAER POLYTECHNIC INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8678528
关键词：
Address Affect Algorithms Anastomosis - action Animals Area Arthritis Bathing Biological Biological Assay Biological Process Biomedical Engineering Biomedical Research Biopsy Bioreactors Bladder Blood Vessels Blood flow Burn injury Cardiovascular Diseases Carotid Arteries Cell Differentiation process Cell Line Cell physiology Cells Chronic Disease Cicatrix Clinical Complex Degenerative Disorder Development Diabetes Mellitus Endothelial Cells Engineering Fluorescence Fluorescent Probes Gene Expression Goals Growth Heart Histology Human Hybrids Image Imagery Imaging Device Immunosuppression Implant In Vitro Inflammation Kidney Kidney Failure Knowledge Label Laboratories Lasers Life Light Liver Liver Failure Measurement Medical Medicine Messenger RNA Methods Modeling Molecular Monitor Morphologic artifacts Natural regeneration Nervous system structure Noise Optical Coherence Tomography Optical Tomography Optics Organ Organ Transplantation Organism Osteoporosis Pathology Patients Performance Phase Photons Physiological Physiology Play Population Dynamics Prevention Process Proteins Regenerative Medicine Reporter Resolution Risk Role Sheep Skeleton Smooth Muscle Myocytes Spinal cord injury Staging Stroke Surface System Systems Biology Techniques Technology Testing Three-Dimensional Image Three-dimensional analysis Time Tissue Engineering Tissues Transplantation Trauma Tubular formation United States National Institutes of Health Vascular System Vascularization base cell motility cell type clinical application clinical practice design human disease implantation improved in vivo innovation interest migration minimally invasive molecular imaging mouse model nerve supply nervous system disorder optical fiber optical imaging preimplantation prototype public health relevance reconstruction repaired research study response scaffold simulation tissue phantom tissue regeneration tomography

项目摘要

DESCRIPTION (provided by applicant): The most important medical challenges include cardiovascular diseases, stroke, degenerative neurological diseases, diabetes, arthritis, osteoporosis, kidney and liver failure, spinal cord injury, burns, battlefield trauma, and other devastating conditions. Organ transplantation addresses some of these needs, but the scarcity of donors and the risk of immune suppression pose major limitations on transplantation. Regenerative medicine seeks to devise new ways to repair or replace damaged tissues and organs for millions of patients who cannot receive transplants. A core technology is the bioengineering of a functional tissue or organ by seeding living cells onto a biodegradable scaffold and then surgically implanting the construct into a patient. Tissue engineering involves extensive remodeling of cells and scaffolds. A major barrier to progress has been the inability to monitor this dynamic complex biological process in real-time, which makes control and optimization extremely difficult. On the other hand, as defined in the NIH roadmap molecular imaging plays an increasingly important role in the advancement of medicine. The optical molecular imaging tools has now allowed much better understanding of biological interactions at molecular and cellular levels in mouse models of almost all human diseases, and found several major clinical applications. Therefore, we are motivated to integrate these two forefront technologies in biomedical research - tissue engineering and optical molecular imaging - in a single unified framework, and drive a paradigm shift from static assays of cellular function in biopsied tissue or 2D culture models towards systematic analysis of 3D systems. The overall goal of this project is to develop a first-of-its-kind multi-probe multi-modal optical molecular tomography system for regenerative medicine and to demonstrate its utility in assessing the bioengineered blood vessels at the pre- and post-implantation stages. Fluorescent probes will be used to label the tubular scaffold and the two main cell types of blood vessels (endothelial cells lining the lumen, and smooth muscle cells in the wall). Optical fibers embedded within the scaffold will deliver laser light for optical coherence tomography and to excite the fluorescent probes. Innovative algorithms will be developed to reconstruct 3D distributions of multiple fluorescent probes. The proposed imaging system will first be used to track the development of bioengineered vessels in 100¿m resolution in a bioreactor mimicking blood flow conditions. Additional fluorescent probes will be used to monitor cell-specific gene expression and verify physiological responses of cells within the engineered vessel. The vessels will then be implanted as interposition grafts in the carotid arteries of living sheep, and will be imaged in 500¿m resolution to follow the tissue regeneration and function. Successful completion of the project will create new optical molecular imaging tools with a demonstrated application in vessel engineering, and have major and lasting impacts on many other areas in regenerative medicine.

描述（由适用提供）：最重要的医学挑战包括心血管疾病，中风，退化性神经系统疾病，糖尿病，关节炎，骨质疏松症，肾脏和肝脏衰竭，脊髓损伤，烧伤，战场创伤和其他毁灭性疾病。器官移植解决了其中一些需求，但是捐助者的稀缺性和免疫抑制的风险对移植产生了主要限制。再生医学旨在为数百万无法接受移植的患者修复或替代受损的组织和器官的新方法。核心技术是通过将活细胞播种到可生物降解的脚手架上，然后手术将构建体实施到患者中，是对功能组织或器官的生物工程。组织工程涉及细胞和支架的大量重塑。进步的主要障碍是无法实时监视这一动态复杂的生物学过程，这使得控制和优化极为困难。另一方面，正如NIH路线图分子成像中所定义的，在医学的进步中起着越来越重要的作用。现在，光学分子成像工具可以更好地了解几乎所有人类疾病的小鼠模型中的分子和细胞水平的生物学相互作用，并发现了几种主要的临床应用。因此，我们有动力将这两种前列技术整合在生物医学研究中 - 组织工程和光学分子成像 - 在一个统一的框架中，并驱动从活检组织中细胞功能或2D培养模型中细胞功能的静态暗示转移到3D系统的系统性分析。该项目的总体目标是开发一种首次使用的多模式的多模式光学分子断层扫描系统，用于再生医学，并在植入植物前和植物后阶段评估其在评估生物工程的血管方面的实用性。荧光探针将用于标记管状支架和血管的两种主要细胞类型（腔内衬里的内皮细胞和壁上的平滑肌细胞）。嵌入支架内的光纤将提供激光光，以进行光学相干断层扫描，并激发荧光探针。将开发创新的算法来重建多个荧光探针的3D分布。提出的成像系统将首先用于跟踪在模仿血液流量条件下的生物反应器中100美元分辨率中生物工程血管的发展。其他荧光探针将用于监测细胞特异性基因表达并验证工程血管内细胞的物理反应。然后，将血管作为插入移植物植入活绵羊的颈动脉，并以500“分辨率成像，以遵循组织再生和功能。该项目的成功完成将创建新的光学分子成像工具，并在船舶工程中展示应用，并对再生医学中许多其他领域产生重大和持久的影响。

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Monte Carlo fluorescence microtomography.

蒙特卡罗荧光显微断层扫描。

DOI：
10.1117/1.3596171
发表时间：
2011
期刊：
Journal of biomedical optics
影响因子：
3.5
作者：
Cong,AlexanderX;Hofmann,MatthiasC;Cong,Wenxiang;Xu,Yong;Wang,Ge
通讯作者：
Wang,Ge

Towards omni-tomography--grand fusion of multiple modalities for simultaneous interior tomography.

DOI：
10.1371/journal.pone.0039700
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Wang G;Zhang J;Gao H;Weir V;Yu H;Cong W;Xu X;Shen H;Bennett J;Furth M;Wang Y;Vannier M
通讯作者：
Vannier M

Bioluminescence tomography with Gaussian prior.