Correlation of Functional and Structural Units in Cerebral Cortex

描述(申请人提供)：大脑皮层功能和结构单位的相关性这项建议是我们早期NIH R21项目的扩展，该项目探索了功能磁共振成像(FMRI)信号和潜在神经元结构之间的空间关系。在同一动物和大脑皮层进行的高分辨率fMRI和组织学联合研究中，我们首次证明了组织fMRI信号在皮质IV层达到峰值。任何基于血流动力学的标测技术的空间特异性都受到潜在的血管网络的约束，因此，两者之间的空间关系对于理解支配和限制这些标测技术的机制至关重要。目前对fMRI对比剂机制的理解，关于其血管起源，是基于大量的假设和理论建模，但几乎没有实验验证来支持或挑战这些模型。由于技术上的限制，目前对脑血管的认识仅限于软膜表面和毛细血管水平的大血管。然而，对于连接这两组的中等大小血管簇，主要是皮质内血管，以及关键的血流调节发生在哪里，人们知之甚少。在我们先前发现的基础上，我们将探索fMRI信号与潜在血管组织的空间对应关系。为了实现拟议的目标，将开展几项多式联运发展。将开发一种新的皮质血管活体可视化和分类(静脉和动脉)方法。利用新的独特的超高场(16.4T/26厘米)磁体，高分辨率MRI采集方案与体外Micro-CT成像相结合，将能够以接近显微镜规模的分辨率对皮质血管系统进行详细和准确的3D建模。此外，还将开发分析工具，以提供血管模型的形态描述和量化。利用这一独特的方法，刺激诱导的fMRI信号变化的空间分布将与相同动物和皮质区域内的潜在血管模型相关。关于功能磁共振成像信号和皮质血管形态，如血管大小和整个组织的空间分布，我们将探讨几种假说。此外，通过仅刺激初级视觉皮质的神经元集合的子集，将生成眼优势和定向柱的3D功能地图，并将其与血管模型相关联。我们将调查这些功能性皮质集合体是否与特定的血管单位偶联。这些研究的结果将是双重的：首先，开发新的和独特的方法学工具，为探索血管模型提供方法。这些技术将被应用于利用血管结构知识的广泛应用；这些应用包括但不限于功能磁共振成像、脑血管疾病、癌症血管生成研究和大脑温度调节模型，所有这些都将极大地受益于准确的血管模型。在第二个结果中，神经生理学研究和临床应用将受益；随着对血管形态和fMRI机制的更好理解，人们可以预期fMRI信号对神经元活动部位的空间定位和空间特异性增加。神经外科计划、癫痫和脑瘤切除等临床应用都将受益于准确度的提高。此外，如果功能(神经元)和结构(血管)单位之间确实存在相关性，在未来，它可能被用作在出现任何临床行为症状之前诊断大脑疾病的工具。公共卫生相关性：功能磁共振成像(FMRI)是一种非侵入性的大脑活动区域定位技术。大脑中神经元活动的增加伴随着少量的局部血流量增加，这可以通过功能磁共振成像来测量。虽然功能磁共振成像已经彻底改变了人脑研究领域，但人们对这些基于血流动力学的信号的潜在血管来源知之甚少。使用强大的磁铁，这项研究的目的是获得极高分辨率的皮质血管图像，生成血管树的三维模型，并将其与功能磁共振信号相关联。这些研究的结果将极大地加深我们对血管网络的了解，并有利于包括功能磁共振成像、脑血管疾病和癌症血管生成在内的各种研究应用。

DESCRIPTION (provided by applicant): Correlation of Functional and Structural Units in Cerebral Cortex This proposal is an expansion of our earlier NIH R21 project that explored the spatial relationship between functional magnetic resonance imaging (fMRI) signals and the underlying neuronal architecture. In a combined high- resolution fMRI and histological study, conducted in the same animal and cortical region, we demonstrated for the first time that tissue fMRI signals peak at cortical layer IV. The spatial specificity of any hemodynamic-based mapping technique is bound by the underlying vascular network; therefore, the spatial relationship between the two is crucial for understanding the mechanisms governing and limiting these mapping techniques. The current understanding of the fMRI contrast mechanism, regarding its vascular origins, is based on numerous assumptions and theoretical modeling, but little experimental validation exists to support or challenge these models. Due to mainly technical limitations, the current knowledge of cerebral vasculature is limited to the large pial surface and capillary level vessels. However, little is known regarding the cluster of intermediate-sized, mainly the intracortical vessels, connecting these two groups and where, arguably, key blood flow regulation takes place. Building on our pervious findings, we will explore the spatial correspondence of fMRI signals with the underlying vascular organization. To accomplish the proposed goal several multimodal developments will be embarked on. A new method for in- vivo visualization and classification (veins and arteries) of cortical vessels will be developed. Utilizing a new and unique ultra high-field (16.4 T / 26 cm) magnet, a high-resolution MRI acquisition schemes combined with ex-vivo micro-CT imaging will enable detailed and accurate 3D modeling of cortical vasculature at resolution approaching the microscopic scale. In addition, analytical tools will be developed to provide morphological description and quantification of the vascular model. Capitalizing on this unique approach, the spatial distribution of stimulus-induced fMRI signal changes will be correlated with the underlying vascular model within the same animal and cortical region. Several hypotheses will be explored with respect to fMRI signals and the cortical vessel morphology such as vessels size and the spatial distributions throughout the tissue. Furthermore, by stimulating only subsets of the neuronal ensemble in primary visual cortex, 3D functional maps of ocular dominance and orientation columns will be generated and correlated with the vascular model. We will investigate whether these functional cortical assemblies are coupled to specific vascular units. The outcome of these studies will be twofold: initially, development of new and unique methodological tools that will provide ways for exploring vascular models. These techniques will be applied to a broad variety of applications that utilize knowledge of the vascular architecture; such application include, but not limited to, fMRI, cerebrovascular diseases, cancer angiogenesis research and models of cerebral thermal regulation all of which will greatly benefit from an accurate vascular model. In the second outcome, neurophysiology research and clinical applications will benefit; with better understanding of the vascular morphology and fMRI mechanism, one can expect the increase in spatial localization and spatial specificity of the fMRI signals to the site of neuronal activity. Clinical applications such as neurosurgery planning, epilepsy and brain tumor resections will all benefit from increased accuracy. Furthermore, if indeed a correlation between functional (neuronal) and structural (vascular) units exist, in the future, it may be used as a diagnostic tool for brain disorders prior to the appearance of any clinical behavioral symptoms. PUBLIC HEALTH RELEVANCE: Functional Magnetic Resonance Imaging (fMRI) is a technique that allows, noninvasively, the localization of active brain regions. Increased neuronal activity in the brain is followed by a small and localized increase in blood flow which can be measured using fMRI. While fMRI has revolutionized the field of human brain research, little is known about the underlying vascular origin of these hemodynamic-based signals. Using a powerful magnet, this study is aims to obtain extremely high-resolution images of cortical vessels, generate a 3-D model of the vascular tree and correlate it with the fMRI signals. The outcome of these studies will greatly enhance our understanding of the vascular network and benefit a variety of research applications including fMRI, cerebrovascular disease, and cancer angiogenesis.