权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Multiphoton In Vivo Microscopy (Core 2)

多光子体内显微镜（核心 2）

基本信息

批准号：
10713243
负责人：
Kyle Patrick Lillis
金额：
$ 27.66万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10713243
关键词：
Algorithms Animals Biophysics Brain Calcium Calibration Chlorides Chronic Custom Data Data Collection Dedications Development Devices Dyes Epileptogenesis Experimental Designs Family suidae Fluorescence Fluorescence Microscopy Funding Image Imaging Device Injections Ions Measurement Measures Microscope Microscopic Microscopy Modeling Molecular Morphologic artifacts Motion Phase Post-Traumatic Epilepsy Procedures Research Resolution Resources Rodent Silicon Speed Technical Expertise Technology Traumatic Brain Injury Trephine hole adeno-associated viral vector cost cost effective data standards design digital extracellular flexibility fluorescence lifetime imaging fluorophore image archival system image registration imaging modality in vivo in vivo imaging in vivo two-photon imaging instrument instrumentation multi-photon multimodal data novel programs serial imaging tool tool development two-photon

项目摘要

Discovering the basic molecular and cellular mechanisms of post-traumatic epileptogenesis in a biophysically realistic model of traumatic brain injury will require having longitudinal, high-resolution access to the gyrencephalic, large animal brain. Fluorescence microscopy enhances such capabilities, enabling multimodal data collection through the use of genetically targeted and ion-selective fluorophores. In the tool development Phase I of this project, we developed an instrument and supporting technologies that afford us the unique ability to perform such measurements. These technologies include a custom two-photon microscope with a gantry design that can accommodate imaging in vivo, with subcellular resolution, brains of animals weighing >80kg. Microscopic in vivo imaging in animals of this size (to our knowledge, the largest by a factor of 2-4x) required substantial development and optimization of motion artifact mitigation tools, including heartbeat-triggered, high speed image stack acquisition; flexible, penetrable, transparent sub-dural windows; and post-hoc image registration algorithms. Finally, the microscope can perform digital fluorescence lifetime imaging, enabling quantification of extracellular chloride using novel single-wavelength dyes. The Microscopy Core will implement the imaging tools developed in Phase I, as well as optimize for calcium imaging and long-term repeated access. As these tools require substantial cost and technical expertise, the Microscopy Core represents a cost-effective consolidation and consistent implementation for the proposed program.

发现创伤后癫痫发生的基本分子和细胞机制