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: 8081078
• 负责人: Paul J Campagnola
• 金额: $ 47.74万
• 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/8081078
• 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的活体成像，为癌症研究带来了特别的希望。 MPLSM 在活体成像方面具有许多优势，包括高分辨率、深切片和提高的组织活力。此外，MPLSM 与二次谐波、荧光寿命和光谱成像方法结合使用时，有望利用内在的对比源，从而消除对外源标记的需要。目前，市场上还没有非常适合体内这项任务的商业 MPLSM 系统。该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。该仪器将允许对侵入局部基质的肿瘤细胞进行成像，通过二次谐波产生（SHG）分析胶原基质的变化，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，特别是那些可能与肿瘤生长、存活、进展、侵袭或转移相关的信号分子。我们提出以下具体目标，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，该系统将包括用于同步强度、光谱和寿命可视化的新软件和硬件。 3. 开发自适应光学系统以纠正系统像差，从而能够从活体标本的更深处采集图像。这些动物研究将为未来成像和可视化方法的发展铺平技术，这些方法有可能改善人类疾病的诊断和分期。我们预计，用户友好的交钥匙多光子显微镜的开发将促进病理学家使用该技术。此外，这些技术未来可能成为手术的辅助手段。通过对动物模型进行成像来了解肿瘤进展将对未来的靶向治疗产生积极影响。公共健康相关性：体内多光子成像改进方法的开发将有助于识别癌症恶性肿瘤的关键特征。了解动物模型中癌症进展的潜在机制可以为人类治疗的未来目标提供建议。