Investigating Tumor Growth Dynamics Using Multimodal Contrast Agents and Optical

使用多模式造影剂和光学研究肿瘤生长动力学

• 批准号: 7830248
• 负责人: Alexander Wei
• 金额: $ 50万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7830248
• 关键词: Address; Area; Biomechanics; Carcinoma; Cells; Coculture Techniques; Complement; Contrast Media; Development; Extravasation; Fibroblasts; Histology; Image; In Vitro; Magnetism; Measurement; Measures; Mechanics; Metric; Multimodal Imaging; Mus; Optical Coherence Tomography; Optics; Plastics; Property; Resolution; Technology; Tensile Strength; Three-Dimensional Imaging; Tissues; Tumor Tissue; Visual; macrophage; migration; nanoparticle; nanoprobe; neoplastic cell; optical imaging; physical science; tumor; tumor growth; tumor xenograft

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-CA-116: Physical Sciences and Cellular Mechanics. We will develop analytical imaging capabilities with complementary nanoparticle probes to measure the viscoelastic properties of cells and tissues in a noninvasive manner. These capabilities will be applied toward understanding biomechanical factors on tumor growth dynamics. Near-infrared (NIR) absorbing Au nanoparticles with magnetic cores will serve as multimodal contrast agents for multiphoton imaging and for magnetomotive optical coherence tomography (MM-OCT) and elastography (MM-OCE), to characterize viscoelastic changes in tumor cells and tissues as a function of their development. Tumor cells will be laden with nanoprobes and cocultured with fibroblasts or macrophages for in vitro multimodal imaging with MM-OCE. Tumor xenografts will also be grown in mice from nanoprobe-laden tumor cells, then excised for ex vivo imaging with results collated with conventional metrics of tumor development (i.e., visual inspection and histology). We anticipate this approach can reveal critical biomechanical differences in the development of invasive carcinomas, in which cells undergo transformations from turgid states with high tensile strength to plastic and deformable states associated with migration and extravasation. Our Specific Aims are as follows: 1) Construction of an integrated optical platform for optical coherence tomography (OCT) and elastography (OCE), for noninvasive imaging of tumor tissues with cellular resolution; 2) Fabrication of nanoprobes that combine plasmon resonance with magnetomotive activity, to generate unique NIR signatures for 3D imaging and elastography; 3) Optimization and deployment of the multimodal imaging platform for simultaneous structural imaging and viscoelastic profiling of nanoprobe-laden tumor cells and excised tumor tissues.

描述（由申请人提供）：本申请涉及广泛的挑战领域（06）使能技术和特定的挑战主题，06-CA-116：物理科学和细胞力学。我们将开发与互补纳米粒子探针的分析成像能力，以非侵入性方式测量细胞和组织的粘弹性。这些能力将被应用于了解肿瘤生长动力学的生物力学因素。具有磁性核的近红外（NIR）吸收Au纳米颗粒将作为多光子成像和磁动光学相干断层扫描（MM-OCT）和弹性成像（MM-OCE）的多模态造影剂，以表征肿瘤细胞和组织中的粘弹性变化作为其发展的函数。肿瘤细胞将负载纳米探针，并与成纤维细胞或巨噬细胞共培养，用于MM-OCE体外多模式成像。肿瘤异种移植物也将在小鼠中从载有纳米探针的肿瘤细胞生长，然后切除用于离体成像，结果与肿瘤发展的常规度量（即，目视检查和组织学）。我们预计这种方法可以揭示浸润性癌发展中的关键生物力学差异，其中细胞从具有高拉伸强度的肿胀状态转变为与迁移和外渗相关的塑性和可变形状态。我们的具体目标如下： 1)光学相干层析成像（OCT）集成光学平台的构建及 弹性成像（OCE），用于具有细胞分辨率的肿瘤组织的非侵入性成像; 2)制造将等离子体共振与磁动活性结合的联合收割机纳米探针， 生成用于3D成像和弹性成像的独特NIR特征; 3)多模态成像平台的优化和部署， 载有纳米探针的肿瘤细胞和切除的肿瘤组织的成像和粘弹性分析。