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: 7258757
• 负责人: Elizabeth M. C. Hillman
• 金额: $ 13.69万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 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 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7258757
• 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电压敏感染料（VSD）和皮质血流动力学的深度分辨光学成像的系统，以便能够研究体内（大鼠）三维（3D）神经血管耦合。神经元激活与相应的血流动力学反应之间的关系对于理解功能激活机制至关重要，尤其与功能磁共振成像（fMRI）的解释相关。一旦引入皮质，VSD 就会根据膜电位按比例改变其荧光，从而表明神经元活动的变化。我们已经开发了一种通过薄化颅骨对大鼠皮质中的氧和脱氧血红蛋白变化进行 3D 光学成像的系统，称为层流光学断层扫描 (LOT)。我们提议改进 LOT.s 的硬件和算法，除了较慢的血流动力学吸收变化之外，还可以对快速、微小的 VSD 荧光变化进行并发 3D 成像。 LOT 系统类似于共焦显微镜，但它不是改变焦深，而是检测多重散射光，可用于以 100-200 微米的分辨率重建深度 >2 毫米的结构图像。迄今为止，VSD 成像使用的是皮质的 2D 相机图像，这些图像的权重非常肤浅，并且不提供深度分辨率。我们同时对 VSD 和血流动力学进行 3D 成像的动机有两个：1) 我们假设，为了正确量化神经活动和血流动力学之间的关系，这两种测量必须在 3D 中空间共定位：2D 荧光和吸收的深度敏感性图像非常不同，因此它们的 2D 像素并不代表皮质中相同的 3D 位置。 2）电生理学已经证明神经元活动是层特异性的。研究神经元激活在皮质层之间移动和传播时的 3D 动力学的非侵入性方法将为研究体内皮质功能活动提供一种全新的方法。我们建议开发荧光-LOT（PLOT），然后使用接受体感刺激的大鼠进行初步系统测试。提高对神经元活动和功能磁共振成像信号之间相关性的理解对于人脑成像至关重要。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。新系统还可应用于眼部、皮肤、内窥镜和肿瘤成像。