Development of fMRI Methods for Neuropharmacology

神经药理学功能磁共振成像方法的发展

• 批准号: 7268864
• 负责人: Shi-Jiang Li
• 金额: $ 32万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268864
• 关键词: Acute; Affect; Agonist; Air; Anesthetics; Animals; Autonomic Agents; Blood; Blood Pressure; Blood Vessels; Brain; Cardiovascular system; Cerebrovascular Circulation; Cerebrum; Chloralose; Class; Cocaine; Complex; Condition; Development; Dose; Drug effect disorder; Echo-Planar Imaging; Electroencephalography; Event; Financial compensation; Functional Magnetic Resonance Imaging; Goals; Halothane; Heart Rate; Heroin; Homeostasis; Human; Image; Invasive; Isoflurane; Laser-Doppler Flowmetry; Link; Magnetic Resonance Imaging; Maps; Measurement; Mediating; Metabolic; Methods; Methoxamine; Modeling; Morphologic artifacts; Motion; Neurobiology; Neurons; Neuropharmacology; Neurosciences Research; Numbers; Oxygen; Oxygen Consumption; Peripheral; Pharmaceutical Preparations; Pharmacology; Physiologic pulse; Physiological; Positioning Attribute; Predisposition; Pulse taking; Range; Rate; Rattus; Research Personnel; Scanning; Signal Transduction; Site; System; Techniques; Technology; Testing; Urethane; awake; blood oxygen level dependent; blood oxygenation level dependent response; brain tissue; cerebrovascular; cognitive function; design; mu opioid receptors; neuroimaging; neuromechanism; programs; receptor; relating to nervous system; research study; respiratory; response

DESCRIPTION (provided by applicant): This proposal is in response to NIBIB RFA EB-03-002, "Systems and Methods for Small Animal Imaging." We will focus on development of functional MRI (fMRI) methods for neuropharmacology in rats. The main goal is to extend application of fMRI method to neuropharmacology. Four specific aims are proposed. For Specific Aim 1, we will determine and characterize the systemic cardiovascular effects induced by anesthetic and autonomic agents on the fMRI blood oxygenation level dependent (BOLD) response in the rat brain produced by forepaw stimulation, a) Determine the dose effects of four anesthetic agents, halothane, isoflurane, alpha-chloralose and urethane, on the functional BOLD response. b) Methoxamine, an alpha-1 receptor agonist that has no direct cerebrovascular effect, will be used to determine if acute increases in mean arterial blood pressure, either within or outside of the physiological range of cerebral blood flow autoregulation, affect the functional BOLD response in the rat brain. Specific Aim 2 is to develop a tailored fMRI pulse sequence on the 3T scanner for overcoming susceptibility artifacts present in air-brain tissue boundaries, to detect BOLD signals in the rat brain. In Specific Aim 3, we will test the hypothesis that fMRI technology is a valid method to map drug-induced activities in the rat brain by using a class of drugs whose pharmacological functions are well characterized. We will test the hypothesis that upon administration of an agonist, fMRI methods can detect BOLD signals originating from the neural events of the agonist-receptor interaction. Further, we will test the hypothesis that such neural events can be blocked by pretreatment or reversed by post treatment with a particular receptor's antagonist. The biggest challenge in extending applications of fMRI technology to neuropharmacology is to interpret the neural mechanisms of the BOLD signals induced by drug administration. In Specific Aim 4, we will develop a biophysical model to calculate cerebral metabolic rate of oxygen consumption (CMRO2) and interpret the BOLD signal changes induced by drugs. We will also conduct Laser Doppler Flowmetry and EEG experiments to validate this biophysical model.

描述（由申请人提供）：本提案是对NIBIB RFA EB-03-002“小动物成像系统和方法”的回应。“我们将专注于开发功能性MRI（fMRI）方法用于大鼠神经药理学。主要目的是将功能磁共振成像方法应用于神经药理学。提出了四个具体目标。对于具体目标1，我们将确定和表征麻醉剂和自主药物对大鼠脑中由前爪刺激产生的fMRI血氧水平依赖性（BOLD）反应诱导的全身心血管效应。a）确定四种麻醉剂氟烷、异氟烷、α-氯醛糖和氨基甲酸乙酯对功能性BOLD反应的剂量效应。B）甲氧胺，一种没有直接脑血管效应的α-1受体激动剂，将用于确定平均动脉血压的急性升高，无论是在脑血流自动调节的生理范围内还是在脑血流自动调节的生理范围外，是否影响大鼠脑中的功能性BOLD反应。具体目标2是在3 T扫描仪上开发定制的fMRI脉冲序列，用于克服存在于空气-脑组织边界中的敏感性伪影，以检测大鼠大脑中的BOLD信号。在具体目标3中，我们将测试的假设，即功能磁共振成像技术是一种有效的方法来映射药物诱导的活动，在大鼠大脑中使用一类药物，其药理学功能是很好的特点。我们将测试的假设，即在管理的激动剂，功能磁共振成像方法可以检测BOLD信号起源于激动剂-受体相互作用的神经事件。此外，我们将测试这样的神经事件可以通过预处理或通过用特定受体的拮抗剂后处理来逆转而被阻断的假设。将功能磁共振成像技术应用于神经药理学的最大挑战是解释由药物给药引起的BOLD信号的神经机制。在具体目标4中，我们将开发一个生物物理模型来计算脑耗氧代谢率（CMRO 2），并解释药物诱导的BOLD信号变化。我们还将进行激光多普勒血流仪和脑电图实验，以验证这一生物物理模型。