Multi-scale mapping of 3D spatial-temporal cortical hemodynamics at the level of

3D 时空皮质血流动力学水平的多尺度映射

• 批准号: 7297230
• 负责人: David Kleinfeld
• 金额: $ 16.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7297230
• 关键词: Arteries; Biological Models; Blood; Blood Vessels; Blood capillaries; Blood flow; Caliber; Cerebrovascular Circulation; Cerebrum; Characteristics; Class; Complex; Cortical Column; Dementia; Dependence; Depth; Detection; Diagnostic; Disruption; Dyes; Electrocorticogram; Erythrocytes; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Histology; Image; Imaging technology; Individual; Knowledge; Label; Laser Scanning Microscopy; Link; Location; Maps; Measurement; Measures; Metabolic; Microscopic; Mitochondria; Nature; Neurons; Optics; Organelles; Outcome; Population; Positioning Attribute; Positron-Emission Tomography; Rattus; Relative (related person); Resolution; Scanning; Signal Transduction; Specificity; Stimulus; Stroke; Surface; Tactile; Techniques; Technology; Testing; Tissues; Ursidae Family; Vascular Diseases; Vasodilation; Vasodilation disorder; Vibrissae; Work; arteriole; base; capillary; data acquisition; density; feeding; hemodynamics; improved; in vivo; light weight; reconstruction; relating to nervous system; response; sensory cortex; sensory stimulus; software development; spatiotemporal; two-photon; vasoconstriction

DESCRIPTION (provided by applicant): The dynamics response of individual neuronal vessels to sensory-stimuli is crucial to form a mechanistic understanding of functional imaging technologies, such as functional MRI (fMRI), as well as for understanding neurovascular dysfunction, as occurs in stroke and dementia. Toward this goal, we propose to characterize the stimulus-evoked cerebral hemodynamic response on the level of single arterioles and capillaries throughout a significant three-dimensional volume. Further, we will relate this characterization to the underlying neuronal electrical activity, the angioarchitecture, and the mitochondria density. Vibrissa sensory cortex of rat serves as our model system. Two-photon laser scanning microscopy (TPLSM), in conjunction with dyes that label the blood lumen, and all-optical histology, a related nonlinear optics technique, serve as our primary technology. As a prerequisite to the proposed measurements, we will improve the capability of TPLSM to allow rapid assessment of multiple blood vessels. This will allow us to characterize blood flow and blood vessel diameter at micrometer resolution throughout a 2 - 3 mm3 volume, along with correlations along flow in different vessels. Our analysis consists of three directions. Dynamical characterization of the diameter and flow dynamics of three classes of vessels, i.e., surface communicating arterioles, penetrating arterioles, and subsurface microvessels, in response to tactile single vibrissa stimulation. Ex vivo reconstruction of the exact angioarchitecture throughout the region of study by the in vivo vascular measurements, followed by three-dimensional mapping of the mitochondria density relative to the microvasculature. Our results will reveal, at a minimum: The characteristics, e.g., biphasic versus monophasic, of the temporal dynamics of the vessel diameter and blood flow changes of individual vessels. The dependence of the responses of a vessel on its distance from the center of the neuronal activity, its connectivity to major surface feeding arteries or penetrating arterioles, and its position relative to the local metabolic need as revealed by the mitochondria density. This work will bridge the critical gap between macroscopic functional imaging technologies such as fMRI and the microscopic understanding of single vessel responses to the neuronal activation. Stroke, vascular disease, and dementia are all dysfunctional states that relate to compromised cerebral blood flow. Our work will define the normal state of flow and bears on disruption to the normal state. It will help define optical- and MRI-based diagnostics for the detection of dysfunction and clinically appropriate interventionist therapies.

描述（由申请人提供）：单个神经元血管对感觉刺激的动态响应对于形成功能成像技术（例如功能 MRI (fMRI)）的机械理解以及理解神经血管功能障碍（如中风中发生的神经血管功能障碍）至关重要和痴呆症。为了实现这一目标，我们建议在整个重要的三维体积中的单个小动脉和毛细血管水平上表征刺激引起的脑血流动力学反应。此外，我们会将这种特征与潜在的神经元电活动、血管结构和线粒体密度联系起来。大鼠触须感觉皮层作为我们的模型系统。双光子激光扫描显微镜 (TPLSM) 与标记血腔的染料以及全光学组织学（一种相关的非线性光学技术）相结合，成为我们的主要技术。作为所提出的测量的先决条件，我们将提高 TPLSM 的能力，以允许快速评估多个血管。这将使我们能够以微米分辨率表征整个 2 - 3 mm3 体积中的血流和血管直径，以及不同血管中流量的相关性。 我们的分析包括三个方向。 响应于触觉单触须刺激，对三类血管（即表面交通小动脉、穿透小动脉和皮下微血管）的直径和流动动力学进行动态表征。 通过体内血管测量，对整个研究区域的精确血管结构进行离体重建，然后绘制线粒体密度相对于微脉管系统的三维图。 我们的结果至少将揭示： 血管直径的时间动态和单个血管的血流变化的特征，例如双相与单相。 血管的反应取决于其距神经元活动中心的距离、其与主要表面供给动脉或穿透小动脉的连接性，以及其相对于线粒体密度所揭示的局部代谢需求的位置。 这项工作将弥合宏观功能成像技术（例如功能磁共振成像）与单血管对神经元激活反应的微观理解之间的关键差距。中风、血管疾病和痴呆都是与脑血流受损有关的功能障碍状态。我们的工作将定义流动的正常状态并影响正常状态的破坏。它将有助于定义基于光学和 MRI 的诊断方法，以检测功能障碍和临床上适当的干预疗法。