Magnetic Resonance Spectroscopic Imaging of the Brain in Methamphetamine Abuse

描述（由申请人提供）：甲基苯丙胺滥用是一个主要的公共卫生问题。甲基苯丙胺滥用的治疗通常在患者刚开始戒断药物的最初几周内成功或失败。在戒酒数周到数年的患者中，已经显示出大脑中各种结构的损伤，但对关键的早期几周期间大脑的状态知之甚少。该提案的长期目标是使用神经成像来表征早期戒断甲基苯丙胺的大脑结构和代谢，以改善患者恢复期间的护理。这与国家卫生研究院延长健康生命和减少疾病和残疾负担的使命高度相关。本提案将使用磁共振成像（MRI）和磁共振光谱成像（MRSI）的神经成像技术。MRI测量大脑结构或“区域”的体积; MRSI测量这些大脑区域内几种化学物质（代谢物）的浓度。MRI和MRSI均对活体人类受试者进行非侵入性工作。这项提议将集中在三个大脑区域：顶叶皮层、下额叶皮层和纹状体。以前在长期戒断滥用甲基苯丙胺者的这三个区域都发现过损害或功能障碍。损害或功能障碍的程度可能会随着患者在戒断前习惯性消耗甲基苯丙胺的量（克/周）而增加。在本提案中，将对13名恢复期甲基苯丙胺依赖受试者和13名年龄和性别匹配的健康对照者进行两次MRI和MRSI扫描。本提案的具体目的是：1）确定对照组和甲基苯丙胺依赖性受试者戒断7天时三个区域中的每一个的体积和代谢物水平是否不同; 2）确定23天后进行的第二次扫描中三个区域中的每一个的体积和代谢物水平是否变化（即，在甲基苯丙胺依赖性受试者戒断30天时）; 3）在甲基苯丙胺依赖性受试者组内，确定扫描1和/或2时的体积和代谢物水平是否随先前消耗的甲基苯丙胺的克/周而变化。如果成功的话，这一提议将确定甲基苯丙胺滥用中的某些大脑异常是否已经存在于非常早期的戒断中，或者它们是否在戒断几周后才首次出现。如果后者是真的，医生可能不得不决定是否有可能和可取的发展与适当的治疗提出这些异常。甲基苯丙胺滥用的治疗通常在最初几周内失败，结果是甲基苯丙胺依赖者继续滥用药物，最终导致在发病率，死亡率和患者护理费用方面更大的公共卫生成本。该提案旨在更好地了解甲基苯丙胺早期戒断期间大脑的状态，以便开发新的疗法并提高现有疗法的成功率。

DESCRIPTION (provided by applicant): Methamphetamine abuse is a major public health problem. Treatment for methamphetamine abuse often succeeds or fails within the first few weeks when the patient just begins to abstain from the drug. Damage to various structures in the brain has been shown in patients abstaining for several weeks to a few years, but little is known about the state of the brain during the critical early weeks. The long-term objective of this proposal is to use neuroimaging to characterize brain structure and metabolism in very early abstinence from methamphetamine in order to improve patient care during recovery. This is highly relevant to the NIH mission to extend healthy life and reduce the burdens of illness and disability. This proposal will use the neuroimaging techniques of Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopic Imaging (MRSI). MRI measures the volumes of structures or "regions" of the brain; MRSI measures the concentrations of several chemicals (metabolites) inside these brain regions. Both MRI and MRSI work non-invasively on living human subjects. This proposal will focus on three brain regions: the parietal cortex, the inferior frontal cortex, and the striatum. Damage or dysfunction has previously been found in each of these three regions in long-term abstinent abusers of methamphetamine. The degree of damage or dysfunction may increase with the amount (grams per week) of methamphetamine habitually consumed by the patient prior to abstinence. In this proposal, MRI and MRSI scans will be performed twice on each of 13 recovering methamphetamine-dependent subjects and 13 age- and gender-matched healthy controls. The specific aims of this proposal are: 1) Determine if volume and metabolite levels of each of the three regions differ between controls and methamphetamine-dependent subjects at 7 days abstinence; 2) Determine if volume and metabolite levels of each of the three regions change in a second scan performed 23 days later (i.e., at 30 days abstinence for methamphetamine-dependent subjects); 3) Within the methamphetamine-dependent subject group, determine if volumes and metabolite levels at scans 1 and/or 2 vary with the grams per week methamphetamine previously consumed. If successful, this proposal will establish whether certain brain abnormalities in methamphetamine abuse are already present in very early abstinence or whether they first appear several weeks into abstinence. If the latter is true, physicians may have to decide whether it is possible and desirable to present these abnormalities from developing with appropriate treatments. Relevance Treatment for methamphetamine abuse often fails within the first few weeks, with the result that methamphetamine-dependent subjects continue to abuse the drug leading eventually to greater public health costs in terms of morbidity, mortality, and patient care expenses. This proposal aims for a better understanding of the state of the brain during very early abstinence from methamphetamine in order to develop novel therapies and improve the success of existing therapies.