Multi-parametric MRI Assessment of Brain Connectivity and Spectroscopic Biomarkers in Patients with a Substance Use Disorder

阿片类药物使用障碍(OUD)在美国已被宣布为公共卫生紧急情况。数据来自 美国疾病控制和预防中心表示，因疟疾死亡人数增加了五倍 1999年至2016年的阿片类药物。神经成像是了解神经回路和生理学的有力工具。 为了有针对性地治疗患有这种疾病的患者。此K23应用程序提供了 专门从事磁共振成像的委员会认证的临床医学物理学家的培训计划 (MRI)，以便接受药物使用障碍的神经科学培训，并成为 独立调查员。此应用程序中设定的目标将建立在候选人的成像物理基础上 背景知识：(1)在物质使用中发展大脑功能和神经回路的基础知识 为成瘾研究设计、优化和解释先进的神经成像技术； (2)接受专业发展培训，成为独立的调查员、导师和 教育工作者；以及(3)接受负责任和合乎道德的科学研究行为的额外培训。这个 整个培训计划将包括一项研究研究，重点是(1)大脑有效连接(即，方向性 OUD中神经回路的连通性)，以及(2)磁共振光谱定量 与这些回路相关的神经递质。在这项拟议的工作中，我们将使用基于fMRI的动态因果关系 利用导师指导的专业知识对有效连通性进行建模，以便识别神经回路 潜在的药物渴求和注意力偏向于挖掘线索。此外，我们将使用磁共振光谱学来 乌拉米中神经递质γ-氨基丁酸和谷氨酸及其相互关系的研究 药物渴求和注意偏向，并探讨这些神经递质与大脑的关系 有效连接。

Opioid use disorder (OUD) has been declared as a public health emergency in the United States. Data from the Centers for Disease Control and Prevention indicate a fivefold increase in the number of deaths due to opioids from 1999 to 2016. Neuroimaging is a powerful tool in understanding the neurocircuitry and physiology of OUD in order to target treatments for patients suffering from this disorder. This K23 application presents a training program for a board-certified clinical medical physicist, who specializes in magnetic resonance imaging (MRI), in order to receive training in the neuroscience of substance use disorders and to become an independent investigator. The goals set in this application will build on the candidate’s imaging physics background by (1) developing a foundational knowledge of brain function and neurocircuitry in substance use disorders in order to design, optimize, and interpret advanced neuroimaging techniques for addiction research; (2) acquiring training in professional development to become an independent investigator, mentor and educator; and (3) receiving additional training in the responsible and ethical conduct of scientific research. The overall training program will involve a research study focused on (1) brain effective connectivity (i.e., directional connectivity) of neural circuits in OUD, and (2) magnetic resonance spectroscopic quantification of neurotransmitters related to these circuits. In this proposed work, we will employ fMRI-based dynamic causal modeling of effective connectivity with guided expertise from mentors in order to identify neurocircuits underlying drug craving and attentional bias to dug cues. In addition, we will use MR spectroscopy to investigate the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in OUD and their relation to drug craving and attentional bias, and to explore the association of these neurotransmitters with brain effective connectivity.