Functional Imaging of The Brain

大脑功能成像

• 批准号: 8158192
• 负责人: Alan Koretsky
• 金额: $ 202.68万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8158192
• 关键词: Address; Brain; Brain region; Computational Technique; Denervation; Detection; Electrophysiology (science); Functional Imaging; Imaging Device; Olfactory Learning; Resolution; conditioned fear

The overall goal of this work is to develop anatomical, functional, and molecular magnetic resonance imaging (MRI) techniques that allow non-invasive assessment of brain function and apply these tools to study plasticity and learning in the rodent brain. MRI techniques are having a broad impact on understanding brain. Anatomical based MRI has been very useful for separating gray and white matter and detecting numerous brain disorders. Functional MRI techniques enable detection of regions of the brain that are active during a task. Molecular MRI is an emerging area, whose major goal is to image a large variety of processes in tissues. The goal of this project is to translate MRI developments in all these areas to study system level changes that occur in the rodent brain during plasticity and learning. Aim 1: Over the past few years, we have completed studies in the rodent brain that acquired very high temporal and spatial resolution functional MRI (fMRI) to monitor changes in hemodynamics as a surrogate marker of electrical activity during forepaw stimulation. Work over the past year has focused on trying to separate macrovascular contribution (draining venuoles) from microvascular contributions (arterioles/capillaries)in mid cortex. The general thinking is that if fMRI maps can be made from microvascular contributions this will more accurately reflect neural function. High spatial and temporal resolution fMRI indicated that significant activation could be detected prior to venuoles contributing in MRI of the whisker barrel cortex. This represents one of the first studies that have directly detected the different contributions of the vascular network to BOLD fMRI. Aim 2: Over the past several years we have demonstrated that manganese chloride enables MRI contrast that defines neural architecture, can monitor activity, and can be used to trace neural connections. Over the last couple of years we have completed the assignment of cortical layers detected using manganese enhanced MRI by comparison to histology and have demonstrated that functional anatomy of several cortical regions of the rodent brain can be defined in individual animals. In particular, clear cytoarchitectural boundaries can be detected between numerous brain areas enabling, for the first time, cytoarchitectural changes to be followed in individual brains over time. Over the past year we have been developing computational techniques that enable automatic and unbiased extraction of anatomical boundaries from these images. This is of growing importance because of recent work from the Duyn group that demonstrates that cytoarchitectural information can be obtained from human MRI. In addition, we have completed studies that trace the laminar inputs of the olfactory pathway from the olfactory bulb to rodent frontal cortex. The anatomic projections from olfactory cortex to frontal cortex have not previously been measured. The manganese based MRI predictions have been confirmed by classical histological based neural tracing techniques. Experiments to assess whether manganese enhanced MRI can detect changes in connections due to olfactory learning and genetic effects in olfactory learning have begun. Aim 3: Functional MRI studies were performed to measure changes in brain activation that occur after denervation of peripheral nerves. Previously we have studied the plasticity that occurs after denervation of the forepaw and hindpaw usign fMRI and demonstrated using manganese enhanced MRI that there were laminar specific changes in cortical inputs and outputs. In order to perform physiological experiments to assess the mechanism for these changes we decided to switch to studying the whisker barrel cortex where much more is known about detailed electrophysiology. Similar to the forepaw and hindpaw, denervation causes plasticity which leads to increased activation along the unaffected pathway and ipsilateral activation in the affected cortex. fMRI and manganese enhanced MRI showed a strengthening of thalalmo-cortical inputs on the unaffected pathway that have been verified in slice electrophysiological studies. This is quite interesting since it is widely believed that in the adult barrel cortex this synpase can not be strengthened. Future work will address the mechanisms for this strenghtening as well as begin to study the basis of the ipsilateral activation detected. Aim 4: We have begun to explore the use of advanced MRI tools for studying simple learning paradigms in the rodent. In order to accomplish this we have been developing techniques that will enable routine fMRI in awake rodents. While fMRI is widely performed in humans and awake primates there have only been a few scattered studies on awake rodents. Training regimens and techniques to hold the head have been developed and intial fMRI results are being obtained. Over the past year we have been able to get consistent fMRI responses due to visual and somatosensory stimulation. The awake rodent fMRI protocol is being used to study brain changes during olfactory induced fear conditioning.

这项工作的总体目标是开发解剖，功能和分子磁共振成像（MRI）技术，该技术允许对脑功能进行非侵入性评估，并应用这些工具来研究啮齿动物大脑中的可塑性和学习。 MRI技术对理解大脑产生了广泛的影响。基于解剖学的MRI对于分离灰质和白质和检测许多脑部疾病非常有用。功能性MRI技术可以检测任务过程中活性的大脑区域。 分子MRI是一个新兴区域，其主要目标是对组织中的各种过程进行成像。该项目的目的是将所有这些领域的MRI开发转换为研究在可塑性和学习过程中啮齿动物大脑中发生的系统水平变化。 AIM 1：在过去的几年中，我们在啮齿动物大脑中完成了研究，这些研究获得了非常高的时间和空间分辨率功能性MRI（fMRI），以监测血液动力学的变化，以作为前言刺激过程中电活动的替代标志。过去一年中的工作集中在尝试将大血管贡献（排水量）与中皮层中的微血管贡献（小动脉/毛细血管）分开。一般认为，如果可以通过微血管贡献制作fMRI地图，这将更准确地反映神经功能。 高空间和时间分辨率fMRI表明，在晶格桶皮层的MRI中，可以检测到明显的激活。 这代表了直接检测到血管网络对大胆fMRI的不同贡献的最早研究之一。 目标2：在过去的几年中，我们证明了氯化锰可以定义神经结构，可以监测活动并可用于追踪神经连接的MRI对比。 在过去的几年中，通过与组织学相比，我们完成了使用锰增强MRI检测到的皮质层的分配，并证明可以在单个动物中定义啮齿动物大脑几个皮质区域的功能解剖结构。 特别是，可以在单个大脑中首次遵循的细胞结构变化之间在许多大脑区域之间检测到明显的细胞结构边界。 在过去的一年中，我们一直在开发计算技术，这些计算技术可以从这些图像中自动且无偏的解剖边界提取。 这是越来越重要的，因为杜林集团的最新工作表明可以从人类MRI获得细胞结构信息。 此外，我们完成了研究，这些研究追踪了从嗅球到啮齿动物额叶皮层的嗅觉途径的层流输入。以前尚未测量从嗅皮层到额叶皮层的解剖概况。 基于锰的MRI预测已通过经典基于组织学的神经跟踪技术证实。 锰增强的MRI是否可以检测嗅觉学习和嗅觉学习中遗传效应引起的连接变化的实验。 AIM 3：进行功能性MRI研究，以测量周围神经修饰后发生的脑激活的变化。 以前，我们已经研究了前爪和后爪usign fMRI之后发生的可塑性，并使用锰增强的MRI证明了皮质输入和输出的层状特异性变化。 为了进行生理实验来评估这些变化的机制，我们决定改用晶须桶皮层，其中更多有关详细电生理学的知识。 与前爪和后爪类似，神经保护导致可塑性，从而导致沿未受影响的途径和同侧激活的激活增加。 fMRI和锰增强的MRI表明，在未受影响的途径上，在SL​​ICE电生理研究中验证了沙拉木皮质输入的增强。 这很有趣，因为人们普遍认为，在成年桶皮层中，这种snpase无法加强。 未来的工作将解决这种策划的机制，并开始研究检测到的同侧激活的基础。 AIM 4：我们已经开始探索使用高级MRI工具来研究啮齿动物中简单学习范例的使用。 为了实现这一目标，我们一直在开发能够在清醒啮齿动物中实现常规fMRI的技术。 虽然fMRI在人类中广泛进行，而清醒灵长类动物只进行了少数关于清醒啮齿动物的分散研究。已经开发了培训方案和固定头的技术，并获得了Intial FMRI结果。 在过去的一年中，由于视觉和体感刺激，我们已经能够获得一致的功能磁共振成像响应。清醒的啮齿动物智能磁共振成像方案用于研究嗅觉引起的恐惧调节期间的大脑变化。