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）改善生理相关动物模型的活体成像，对癌症研究具有特别的前景。MPLSM对于活体成像具有许多优点，包括高分辨率、深切片和改善的组织活力。此外，MPLSM与二次谐波，荧光寿命和光谱成像方法相结合时，有希望利用内在的对比度来源，从而减少对外源性标记的需要。目前，市场上还没有非常适合于该体内任务的商业MPLSM系统。研究的总体目标是为Prairie Technologies Ultima IV MPSLM添加新的多模态功能，用于癌症进展动物模型的活体显微镜检查。该仪器将允许侵入局部基质的肿瘤细胞成像，通过二次谐波产生（SHG）分析胶原基质中的变化，可视化伴随肿瘤生长和进展的代谢变化，以及研究体内信号分子，特别是可能与肿瘤生长、存活、进展、侵入或转移相关的那些。我们提出了以下具体目标，通过这些目标，我们将增强Ultima的能力，以实现这些目标。1.开发用于SHG信号采集和分析的光学和软件方法2.为Ultima IV开发一个新的采集系统，该系统将包括新的软件和硬件，用于同时进行强度、光谱和寿命可视化。3.开发一个自适应光学系统，用于校正系统像差，以便从活体标本的更深处获取图像。这些动物研究将为成像和可视化方法的未来发展铺平技术，这些方法有可能改善人类疾病的诊断和分期。我们设想，一个用户友好的，交钥匙多光子显微镜的发展将促进病理学家使用这项技术。此外，这些技术可能是未来手术的辅助手段。通过动物模型成像来了解肿瘤进展将对未来的治疗产生积极影响。公共卫生相关性：改进的体内多光子成像方法的发展将有助于识别癌症恶性程度的关键特征。了解动物模型中癌症进展的潜在机制可以为人类治疗提供未来的靶点。