Magnetic Resonance Spectroscopic Imaging of the Brain in Methamphetamine Abuse

描述(申请人提供)：滥用甲基苯丙胺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开始戒毒的最初几周内成功或失败。在戒酒几周到几年的患者中，大脑的各种结构都受到了损害，但人们对关键早期几周的大脑状态知之甚少。这项建议的长期目标是使用神经成像来表征甲基苯丙胺戒断早期的大脑结构和代谢，以改善康复期间的患者护理。这与美国国立卫生研究院延长健康寿命、减轻疾病和残疾负担的使命高度相关。这项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。核磁共振测量大脑结构或“区域”的体积；核磁共振成像测量这些大脑区域内几种化学物质(代谢物)的浓度。核磁共振成像和核磁共振成像在活体人体上都是非侵入性的。这项提议将集中在三个大脑区域：顶叶皮质、额叶下部皮质和纹状体。此前，在这三个区域中的每一个区域都发现了长期禁欲的甲基苯丙胺滥用者的损害或功能障碍。损害或功能障碍的程度可能会随着患者在戒毒前习惯性消耗的甲基苯丙胺的量(克/周)而增加。在这项提案中，将对13名正在康复的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每人进行两次MRI和MRSI扫描。这项建议的具体目的是：1)确定对照组和甲基苯丙胺依赖者在戒断7天时三个区域中每一个区域的体积和代谢物水平是否不同；2)确定在23天后进行的第二次扫描中，三个区域中每个区域的体积和代谢物水平是否发生变化(即，在甲基苯丙胺依赖者戒断30天时)；3)在甲基苯丙胺依赖受试者组内，确定扫描1和/或2的体积和代谢物水平是否随以前消费的每周甲基苯丙胺的克而变化。如果成功，这项提议将确定甲基苯丙胺滥用中的某些大脑异常是在戒酒初期就已经出现，还是在戒酒几周后首次出现。如果后者是真的，医生可能不得不决定是否有可能和希望通过适当的治疗来表现这些发育异常。甲基苯丙胺滥用的相关治疗往往在最初几周内失败，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。这项建议旨在更好地了解在甲基苯丙胺非常早期戒除期间的大脑状态，以便开发新的疗法并提高现有疗法的成功。

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.