Development of The Prairie Technologies MPLSM to image cancer models in vivo

The Prairie Technologies 开发 MPLSM 以对体内癌症模型进行成像

• 批准号: 8258304
• 负责人: Paul J Campagnola
• 金额: $ 45.99万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8258304
• 关键词: Algorithms; Animal Cancer Model; Animal Model; Animals; Back; Biological; Breast Carcinoma; Cancer Model; Carcinoma; Cells; Collaborations; Collagen; Collection; Communities; Computer software; Coupled; Data Collection; Development; Diagnosis; Disease; Electronics; Event; Fluorescence; Future; Generations; Goals; Health; Human; Image; Image Analysis; Imagery; Invaded; Investigation; Label; Laboratories; Laser Scanning Microscopy; Life; Light; Malignant Neoplasms; Mammary gland; Marketing; Metabolic; Methods; Microscope; Morphology; Neoplasm Metastasis; Operative Surgical Procedures; Optical Instrument; Optics; Pathologist; Performance; Photons; Process; Research; Research Personnel; Resolution; Sampling; Scanning; Signal Transduction; Signaling Molecule; Source; Specimen; Staging; System; Technology; Testing; Time; Tissue Viability; Tissues; adaptive optics; base; biological research; cancer imaging; design; digital; flexibility; human disease; image visualization; improved; in vivo; instrument; instrumentation; interest; intravital microscopy; light scattering; malignant breast neoplasm; multidisciplinary; multimodality; neoplastic cell; new technology; novel; open source; programs; public health relevance; response; second harmonic; sensor; simulation; tool; tumor; tumor growth; tumor progression; user-friendly

DESCRIPTION (provided by applicant): The use of multiphoton laser scanning microscopy (MPLSM) to improve intravital imaging in physiologically relevant animal models holds particular promise for cancer studies. MPLSM has many advantages for intravital imaging, including high resolution, deep sectioning, and improved tissue viability. Moreover, MPLSM when coupled with second harmonic, fluorescent lifetime and spectral imaging approaches holds the promise of exploiting intrinsic sources of contrast that obviate the need for exogenous labels. Currently, there are no commercial MPLSM systems on the market that are well suited for this task in vivo. The overall objective of the research aims is to add new multimodality functionality to the Prairie Technologies Ultima IV MPSLM for intravital microscopy in animal models of carcinoma progression. This instrument will permit imaging of tumor cells invading into local stroma, analysis of changes in the collagen stroma by second harmonic generation (SHG), visualization of metabolic changes that accompany tumor growth and progression, and investigation of signaling molecules in vivo, especially those that may be relevant to tumor growth, survival, progression, invasion, or metastasis. We propose the following specific Aims, through which we will augment the capabilities of the Ultima to achieve these goals. 1. Develop optical and software approaches for SHG signal collection and analysis 2. Develop an new acquisition system for the Ultima IV that will consist of new software and hardware for simultaneous intensity, spectral and lifetime visualization. 3. Develop an adaptive optics system for correct system aberrations to enable image acquisition from deeper within living specimens. These animal studies will pave the technology for future development of imaging and visualization approaches that have the potential to improve the diagnosis and staging of human disease. We envision that the development of a user-friendly, turn-key multiphoton microscope will facilitate the use of this technology by pathologists. Moreover, these technologies could be a future adjunct to surgery. The understanding of tumor progression that will result from imaging animal models will have a positive impact on targeting future therapies. PUBLIC HEALTH RELEVANCE: The development of improved methods for in vivo multiphoton imaging will help identify key signatures of malignancy of cancer. Understanding the underlying mechanisms of cancer progression in animal models can suggest future targets for human therapy.

描述（由申请人提供）：使用多光子激光扫描显微镜（MPLSM）来改善生理相关动物模型中的经液成像，这对癌症研究具有特别的希望。 MPLSM在插入成像方面具有许多优势，包括高分辨率，深部切割和提高的组织生存能力。此外，MPLSM与第二个谐波，荧光寿命和光谱成像方法相结合时，有望利用固有的对比来源，以消除对外源标记的需求。目前，市场上没有商业MPLSM系统在体内适合此任务。该研究的总体目的是在癌癌进展动物模型中，在草原技术Ultima IV MPSLM中添加新的多模式功能。该仪器将允许对入侵局部基质的肿瘤细胞进行成像，通过第二次谐波产生（SHG）对胶原基质的变化进行分析，伴随肿瘤生长和进展的代谢变化的可视化以及体内信号分子的研究，尤其是那些可能与肿瘤的生长，生存，进展，进展，入侵，入侵，进展，侵袭，或转移。我们提出以下特定目标，通过这些目标，我们将增强Ultima实现这些目标的能力。 1。开发用于SHG信号收集和分析的光学和软件方法2。为Ultima IV开发新的采集系统，该系统将由新软件和硬件组成，用于同时强度，频谱和寿命可视化。 3。开发一种自适应光学系统，用于正确的系统畸变，以使从生物标本内更深入地获取图像。这些动物研究将为未来开发成像和可视化方法的开发铺平技术，这些方法有可能改善人类疾病的诊断和分期。我们设想，开发用户友好的，交钥匙多光子显微镜将有助于病理学家使用该技术。此外，这些技术可能是手术的未来辅助手段。成像动物模型会导致肿瘤进展的理解将对靶向未来疗法产生积极影响。公共卫生相关性：开发改进的体内多光子成像方法将有助于确定癌症恶性肿瘤的关键签名。了解动物模型中癌症进展的潜在机制可以表明未来的人类治疗目标。