A Depth-resolved Voltage Sensitive Dye Imaging System

深度分辨电压敏感染料成像系统

• 批准号: 7017264
• 负责人: Elizabeth M. C. Hillman
• 金额: $ 9.19万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-16 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017264
• 关键词: bioimaging /biomedical imaging; biomedical equipment development; brain imaging /visualization /scanning; cerebral cortex; cerebrovascular imaging /visualization; computer program /software; computer simulation; computer system design /evaluation; computer system hardware; fluorescent dye /probe; hemodynamics; image processing; laboratory rat; membrane potentials; optical tomography; three dimensional imaging /topography

DESCRIPTION (provided by applicant): We propose to develop a system for depth-resolved optical imaging of both voltage sensitive dyes (VSDs) and cortical hemodynamics, to enable study of three-dimensional (3D) neurovascular coupling in-vivo (rats). The relationship between neuronal activation and the corresponding hemodynamic response is of fundamental importance for understanding the mechanisms of functional activation, and particularly relevant to interpretation of functional magnetic resonance imaging (fMRI). Once introduced into the cortex, VSDs change their fluorescence proportionally to membrane potential, thereby indicating changes in neuronal activity. We have already developed a system for 3D optical imaging of oxy and deoxy-hemoglobin changes in rat cortex through thinned skull, called Laminar Optical Tomography (LOT). We are proposing to advance LOT.s hardware and algorithms to allow concurrent 3D imaging of rapid, small VSD fluorescence changes in addition to slower hemodynamic absorption changes. The LOT system is similar to a confocal microscope, but rather than varying focal depth, it detects multiply scattered light, which can be used to reconstruct images of structures to depths of >2mm with 100-200 micron resolution. VSD imaging to date has utilized 2D camera images of the cortex, which are very superficially weighted and provide no depth-resolution. Our motivation to simultaneously image VSDs and hemodynamics in 3D is twofold: 1) We hypothesize that to properly quantify the relationship between neural activity and hemodynamics, the two measures must be spatially co-localized in 3D: The depth-sensitivities of 2D fluorescence and absorption images are very different, and so their 2D pixels do not represent the same 3D locations in the cortex. 2) Electrophysiology has demonstrated that neuronal activity is layer-specific. A non-invasive way to study the 3D dynamics of neuronal activation as it moves and spreads between cortical layers would provide a completely new way to study cortical functional activity in-vivo. We propose to develop Fluorescent-LOT (PLOT) and then perform preliminary system testing using rats undergoing somatosensory stimulus. Improved understanding of the correlation between neuronal activity and fMRI signals is of prime importance to human brain imaging. The effects of abnormal pathologies on neurovascular coupling could provide new insights for treatment and prevention. The new system could also find applications in ocular, dermal, endoscopic and tumor imaging.

描述（由申请人提供）：我们建议开发一种用于对电压敏感染料（VSD）和皮质血流动力学的深度分解光学成像的系统，以便研究三维（3D）神经血管偶联的研究（大鼠）。神经元激活与相应的血液动力学反应之间的关系对于理解功能激活的机制至关重要，并且与功能磁共振成像（fMRI）的解释尤其重要。一旦引入皮层，VSD会按比例地改变其荧光与膜电位，从而表明神经元活性的变化。我们已经开发了一种用于通过稀薄的头骨（称为层状光学层析成像（LOT））的大鼠皮层中氧和脱氧 - 血红蛋白变化的3D光学成像的系统。我们提出要推进批次。硬件和算法允许同时进行3D成像，除了较慢的血液动力学吸收变化外，快速，小VSD荧光变化。批次系统类似于共聚焦显微镜，但它没有改变焦点深度，而是检测到乘散射的光，可用于重建结构图像，并以100-200微米的分辨率重建> 2mm的深度。迄今为止，VSD成像利用了皮质的2D摄像头图像，这些摄像头非常表面化，没有提供深度分辨率。 Our motivation to simultaneously image VSDs and hemodynamics in 3D is twofold: 1) We hypothesize that to properly quantify the relationship between neural activity and hemodynamics, the two measures must be spatially co-localized in 3D: The depth-sensitivities of 2D fluorescence and absorption images are very different, and so their 2D pixels do not represent the same 3D locations in the cortex. 2）电生理学表明神经元活性是特异性的。一种非侵入性研究神经元激活的3D动力学，因为它在皮质层之间移动和扩散将为研究皮质功能活性提供一种全新的方法。我们建议开发荧光lot（图），然后使用经历体感刺激的大鼠进行初步系统测试。对神经元活性与fMRI信号之间的相关性的了解对人脑成像至关重要。异常病理对神经血管耦合的影响可以为治疗和预防提供新的见解。新系统还可以在眼部，皮肤，内窥镜和肿瘤成像中找到应用。