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: 7446162
• 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 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7446162
• 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力学响应对于形成对功能成像技术（如功能性MRI（fMRI））的机械理解以及理解神经血管功能障碍（如中风和痴呆）至关重要。为了实现这一目标，我们建议在一个显着的三维体积上的单个小动脉和毛细血管的水平上表征刺激诱发的脑血流动力学反应。此外，我们将这种特性与潜在的神经元电活动，血管结构和线粒体密度。以大鼠触须感觉皮层为模型系统。双光子激光扫描显微镜（TPLSM），结合染料标记的血腔，和全光学组织学，相关的非线性光学技术，作为我们的主要技术。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。这将使我们能够在2 - 3 mm 3体积内以微米分辨率表征血流和血管直径，沿着不同血管中沿血流的相关性。 我们的分析包括三个方向。 三类血管直径和流动动力学的动态表征，即，表面交通小动脉、穿透小动脉和表面下微血管对触觉单触须刺激的反应。 通过体内血管测量对整个研究区域的精确血管结构进行体外重建，然后对线粒体密度相对于微血管进行三维绘图。 我们的研究结果将至少揭示： 特征，例如，双相与单相，血管直径的时间动态和单个血管的血流变化。 血管的反应依赖于其与神经元活动中心的距离、其与主要表面供血动脉或穿透性小动脉的连通性以及其相对于局部代谢需要的位置，如线粒体密度所揭示的。 这项工作将弥合宏观功能成像技术，如功能磁共振成像和微观理解的单血管神经元激活的反应之间的关键差距。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，并对正常状态的破坏产生影响。它将有助于定义基于光学和MRI的诊断，用于检测功能障碍和临床上适当的干预治疗。