High Resolution Spectroscopic Imaging of Mouse Brain

小鼠大脑的高分辨率光谱成像

• 批准号: 6708552
• 负责人: Hoby P Hetherington
• 金额: $ 24.85万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-05 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6708552
• 关键词: aspartate; bioimaging /biomedical imaging; biomedical automation; brain imaging /visualization /scanning; brain metabolism; computer data analysis; epilepsy; gamma aminobutyrate; glutamates; image processing; laboratory mouse; method development; nuclear magnetic resonance spectroscopy

DESCRIPTION (provided by applicant): In human studies of epilepsy, measurements of NAA have been widely used to assess neuronal loss and damage to localize seizure loci in a variety of different epileptic pathologies. Decreases in cerebral GABA (the primary inhibitory neurotransmitter) have been shown to be widespread and its metabolism and receptor systems are the target of a wide variety of anti-epileptic medications. Similarly, glutamate (the primary excitatory neurotransmitter) may be elevated in the epileptogenic hippocampus. However, mechanistic studies in humans are often difficult to pursue due to varying treatment regimens, medical history and the often poorly defined origin of the seizures. Therefore, mouse models of epilepsy are of great importance in evaluating the biochemical mechanisms underlying epiteptogenesis. Despite the clear ability of MR spectroscopic imaging to localize seizure foci, map the metabolic effects through networked structures, monitor alterations in critical neurotransmitter systems and by its non-invasive nature monitor the progression of epileptogenesis, its application in mouse models has been hinted. The lack of applications in the mouse brain is a direct reflection of a number of technological limitations including: 1) difficulties with shimming due to strong susceptibility effects associated with the small size of the mouse brain and proximity of bony and air-filled passages to brain tissue; 2) SNR limitations and volume resolution effects due to the relatively small size of the brain within the skull; 3) regional heterogeneity in metabolite content and its effects on interpretation of acquired data. Therefore the overall goal of this proposal is to develop the tools required to reproducibly acquire and analyze high-resolution spectroscopic images of NAA, glutamate and GABA in the mouse brain.

描述（由申请人提供）：在人类癫痫研究中，NAA 的测量已被广泛用于评估神经元损失和损伤，以定位各种不同癫痫病理中的癫痫位点。大脑 GABA（主要抑制性神经递质）的减少已被证明是普遍存在的，其代谢和受体系统是多种抗癫痫药物的目标。同样，致癫痫海马中的谷氨酸（主要兴奋性神经递质）可能会升高。然而，由于不同的治疗方案、病史以及癫痫发作的起源往往不明确，因此人类的机制研究通常很难进行。因此，小鼠癫痫模型对于评估表位发生的生化机制非常重要。尽管磁共振波谱成像具有明确的能力来定位癫痫病灶、通过网络结构绘制代谢效应图、监测关键神经递质系统的变化以及通过其非侵入性性质监测癫痫发生的进展，但其在小鼠模型中的应用已被暗示。在小鼠大脑中缺乏应用直接反映了许多技术限制，包括：1）由于与小鼠大脑尺寸较小以及骨和充满空气的通道接近大脑相关的强烈敏感性效应，匀场困难组织; 2) 由于颅骨内大脑的尺寸相对较小，导致信噪比限制和体积分辨率影响； 3) 代谢物含量的区域异质性及其对获取数据解释的影响。因此，该提案的总体目标是开发可重复获取和分析小鼠大脑中 NAA、谷氨酸和 GABA 的高分辨率光谱图像所需的工具。