MULTIPHOTON MICROSCOPY FOR IN VIVO NEURAL IMAGING

用于体内神经成像的多光子显微镜

• 批准号: 7563694
• 负责人: Brian J Bacskai
• 金额: $ 0.61万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7563694
• 关键词: Address; Alzheimer' s Disease; Animals; Biological; Brain; Brain imaging; Cells; Computer Retrieval of Information on Scientific Projects Database; Depth; Detection; Development; Diagnostic Procedure; Disease; Disease model; Experimental Models; Functional disorder; Funding; Grant; Human; Image; Imaging Techniques; Individual; Institution; Invasive; Investigation; Lasers; Lead; Life; Light Microscope; Magnetic Resonance Imaging; Methods; Microglia; Microscopic; Microscopy; Molecular Structure; Mus; Neurons; Non-Invasive Cancer Detection; Patients; Physiology; Positron-Emission Tomography; Procedures; Process; Reagent; Reporter; Research; Research Personnel; Resolution; Resources; Senile Plaques; Source; Structure; Techniques; Tissues; Transgenic Mice; Transgenic Organisms; United States National Institutes of Health; Use of New Techniques; base; cellular imaging; clinically relevant; detector; fluorophore; in vivo; insight; molecular imaging; molecular/cellular imaging; mouse model; relating to nervous system; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): In vivo imaging of cellular and molecular structures in the intact brain provides a powerful tool for wideranging investigations in normal physiology, or in experimental models of disease processes. We have recently developed methods using a light microscope-based technique, multiphoton microscopy, to image microscopic structures in the brains of living transgenic mice over periods of months. Multiphoton microscopy utilizes a near-infrared laser for excitation of fluorophores deep within scattering tissue, with high spatial and temporal resolution. The spatial resolution of this imaging technique is about 1micrometer, several orders of magnitude better than other in vivo techniques, like PET, or MRI. In this application, we propose to develop new techniques that will provide important in rive readouts for biological imaging. This research will also lay the groundwork for development of contrast reagents suitable for use in human brain imaging with PET or MRI. We will develop, in Aim 1, techniques for high-resolution, in vivo imaging of structural reporters in the brain. We will investigate procedures to image individual neurons and microglia with high spatial resolution in the intact brain. In Aim 2, we propose to develop imaging techniques that exploit functional reporters in these living cells in the brain. Development of these molecular imaging techniques will build upon techniques accomplished in Aim 1. We have been using an experimental, transgenic mouse model of Alzheimer's disease that develops senile similar to those found in patients with Alzheimer's disease (AD). Our imaging techniques have allowed us to image the senile plaques in vivo in these mice with high spatial resolution. We will apply our new imaging techniques to this mouse model and address important questions that will provide insight into the pathophysiology of this disease. Our current techniques, however, rely on invasive procedures to gain access to the brain for imaging. In Aim 3, we will develop new techniques for non-invasive, in rive detection of senile plaques. New techniques using nearinfrared contrast reagents, and IR-sensitive detectors will allow non-invasive detection of plaques in the intact animal, and may also lead to clinically relevant diagnostic procedures for AD patients. In summary, the proposals outlined in this application will lead to generally applicable new techniques for cellular and molecular imaging in the intact brain.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 描述（由申请人提供）：完整大脑中细胞和分子结构的体内成像为正常生理学或疾病过程实验模型的广泛研究提供了强大的工具。我们最近开发了使用基于光学显微镜的技术（多光子显微镜）的方法，可以在数月的时间内对活的转基因小鼠的大脑中的微观结构进行成像。多光子显微镜利用近红外激光激发散射组织深处的荧光团，具有高空间和时间分辨率。这种成像技术的空间分辨率约为 1 微米，比 PET 或 MRI 等其他体内技术好几个数量级。在此应用中，我们建议开发新技术，为生物成像的河流读数提供重要的信息。这项研究还将为开发适用于 PET 或 MRI 人脑成像的造影剂奠定基础。在目标 1 中，我们将开发大脑结构报告基因的高分辨率体内成像技术。我们将研究在完整大脑中以高空间分辨率对单个神经元和小胶质细胞进行成像的程序。在目标 2 中，我们建议开发成像技术，利用大脑中这些活细胞的功能报告基因。这些分子成像技术的开发将建立在目标 1 所实现的技术的基础上。我们一直在使用阿尔茨海默病的实验性转基因小鼠模型，该模型会出现与阿尔茨海默病 (AD) 患者相似的衰老症状。我们的成像技术使我们能够以高空间分辨率对这些小鼠体内的老年斑进行成像。我们将把我们的新成像技术应用于这种小鼠模型，并解决重要问题，从而深入了解这种疾病的病理生理学。然而，我们目前的技术依赖侵入性手术来进入大脑进行成像。在目标 3 中，我们将开发非侵入性实时检测老年斑的新技术。使用近红外对比试剂和红外敏感探测器的新技术将允许对完整动物中的斑块进行非侵入性检测，并且还可能为 AD 患者带来临床相关的诊断程序。总之，本申请中概述的建议将带来普遍适用的完整大脑细胞和分子成像新技术。