fMRI Technique Development for Substance Abuse Research

描述：（申请人提供） 这是一项通过“指导量化”项目提供5年资金的请求， 研究职业奖”（K25）机制。申请人A 生物制药师/电气工程师，提出了一个培训计划， 神经科学和药理学。申请人的长期目标是成为 一个独立的和跨学科的研究者，熟练的应用程序 磁共振方法用于药物滥用研究。的 该奖项的研究部分将开发和改进功能磁 用于研究药物滥用的核磁共振成像（fMRI）技术， 人类实验对象的成瘾这些技术将被应用于研究 可卡因对人体的影响性虐待是一个严重的公共问题 具有重要精神病学、医学和药物滥用政策的健康问题 影响可卡因急性给药改变中枢神经系统 (CNS)神经元活动和脑血流量;长期使用可卡因可以 导致长期的神经元和行为变化，以及 脑血管功能功能磁共振成像使用血氧变化来估计 神经元活动，时间分辨率为几秒，空间分辨率为几秒 几毫米的分辨率。然而，信噪比（SNR）和 时间分辨率限制对当前可以 在体内测量。提出了三项单独的技术开发工作。 首先，相控阵回波平面成像系统，优化的研究， 大脑区域可能介导可卡因的奖励作用， 在4特斯拉MR扫描仪上实现。该系统将大大提高 功能磁共振成像的信噪比，并允许检测可卡因诱导的改变， 腹侧纹状体、丘脑和后部新皮质的神经元活动 个别科目。第二，一种快速同时评估 由蓝光和红光引起的相对BOLD激活将是 开发的时间分辨率至少为一次测量， 一分钟，以确定可卡因对颜色视觉的影响之间的关系， 处理（多巴胺能改变的代理）和其他大脑中的激活 地区第三，将进行一系列实验研究，以确定 EEG α活动（ 药物诱导的欣快症）和BOLD光反应。这项研究可能有助于 开发用于评估EEG α活动的磁共振方法， 对各种药物的兴奋作用进行客观测量。的 这项研究的长期目标是更好地了解 因此，更好的预防和治疗战略 可以开发和评估。

DESCRIPTION: (provided by applicant) This is a request for 5 years of funding through the "Mentored Quantitative Research Career Award" (K25) mechanism. The applicant, a biophysicist/electrical engineer, proposes a program of training in neuroscience and pharmacology. The long term goal of the applicant is to become an independent and interdisciplinary investigator, skilled in the application of magnetic resonance methods for the study of substance abuse research. The research component of this award will develop and improve functional magnetic resonance imaging (fMRI) techniques for the study of substance abuse and addiction in human subjects. These techniques will be applied to study the effects of cocaine administration in humans. Cocaine abuse is a serious public health problem having important psychiatric, medical, and drug abuse policy implications. Acute administration of cocaine alters central nervous system (CNS) neuronal activity and cerebral blood flow; chronic use of cocaine can lead to long term neuronal and behavioral changes, as well as to alterations in cerebral vascular function. fMRI uses blood oxygenation changes to estimate neuronal activity, with a temporal resolution of several seconds and spatial resolution of a few millimeters. However, signal to noise ratio (SNR) and temporal resolution limits put constraints on the parameters that can currently be measured in vivo. Three separate technical development efforts are proposed. First, a phased array echoplanar imaging system, optimized for the study of brain regions which may mediate the rewarding effects of cocaine, will be implemented on a 4 Tesla MR scanner. This system will significantly increase the SNR of fMRI, and allow the detection of cocaine-induced alterations in neuronal activity in ventral striatum, thalamus, and posterior neocortex in individual subjects. Second, a method for rapidly and simultaneously assessing the relative BOLD activation resulting from blue and red light will be developed with a time resolution of at least one multicolor measurement per minute to determine the relationship between cocaine's effects on color visual processing (a proxy for dopaminergic alterations) and activation in other brain regions. Third, a set of experimental studies will be conducted to determine the relationship between EEG alpha activity (a surrogate marker for drug-induced euphoria) and the BOLD photic response. This study may aid in the development of magnetic resonance methods for assessing EEG alpha activity, giving an objective measure of the euphorigenic effects of various drugs. The long term goals of this research are to provide a better understanding of the phenomenon of cocaine abuse so that better prevention and treatment strategies can be developed and evaluated.