Magnetic resonance imaging of lithium in human brain

人脑中锂的磁共振成像

• 批准号: 7588586
• 负责人: Richard A Komoroski
• 金额: $ 23.49万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588586
• 关键词: Anterior; Bipolar Disorder; Brain; Brain region; Cessation of life; Clinical; Development; Diagnostic; Disease; Drug Kinetics; Electronics; Elements; Equilibrium; Fatty acid glycerol esters; Fourier Transform; Head; Human; Hydrogen; Image; Indium; Isotopes; Laboratories; Lead; Lithium; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Medicine; Mental disorders; Methodology; Methods; Modeling; Patients; Pharmaceutical Preparations; Physiologic pulse; Population; Property; Relative (related person); Relaxation; Research; Resolution; Role; Sampling; Signal Transduction; Slice; Spatial Distribution; Staging; Symptoms; Testing; Therapeutic; Time; Tissues; Universities; Variant; Water; base; brain cell; clinical effect; college; design; effective therapy; experience; human subject; imaging modality; improved; in vivo; magnetic field; neurochemistry; neurotoxic; novel; public health relevance; spectroscopic imaging; success; tool

DESCRIPTION (provided by applicant): Lithium (Li) is still a mainstay for the treatment of bipolar disorder (manic-depressive illness). Despite considerable research, Li's mechanism of action and regional distribution in brain are unknown. The symptoms of bipolar disorder suggest that certain brain regions are primarily involved in the illness. For example, abnormalities have been observed in brain regions known as the anterior limbic network. It is likely that Li's clinical effects in bipolar disorder arise from its effects in these brain regions and not from its presence in brain overall. Understanding the regional distribution of Li within the brain would clarify Li's mechanisms of therapeutic actions, neurotoxic effects, and the wide variations in patients' responsiveness to the drug. It would determine whether Li is achieving sufficient concentrations in critical brain regions. Magnetic resonance imaging (MRI) is a powerful clinical diagnostic tool. In standard clinical MRI, image contrast is provided primarily by differences in a variety of MRI signal parameters from hydrogen (1H) in tissue water. It is possible to generate MRI signals from elements other than 1H, such as 7Li, to provide a map of that element in the brain. For 7Li MRI, early attempts to map the spatial distribution of Li in the brain of a patient on Li therapy were unsuccessful. The low concentration of Li (~1 mM) in the brain during treatment, the lower sensitivity of 7Li relative to 1H, and the very long spin-lattice relaxation time (T1) made 7Li MRI too insensitive to provide usable information. Now these problems can be overcome by sensitivity increases from higher-magnetic-field scanners, improved electronics, and new MRI pulse sequences to reduce the effect of long T1. We will develop and implement in vivo 7Li MRI on a 4-T MRI research scanner in the Center for Imaging Research in the University of Cincinnati College of Medicine. The specific aims of this proposal are: 1) to compare a standard gradient echo, low-tip-angle MRI sequence, a spin-echo, large-tip-angle MRI sequence, and a short-echo-time driven-equilibrium Fourier transform MRI sequence in test samples to determine the optimum sequence for in vivo 7Li MRI measurements; and 2) using the optimum 7Li MRI approach from Specific Aim 1, measure the distribution of Li in the brains of 10 patients being treated with Li for bipolar disorder and at steady state as a test of the validity of the method. PUBLIC HEALTH RELEVANCE: Lithium is an important treatment for bipolar disorder, a devastating mental illness that occurs in about 3% of the population. Understanding how lithium distributes itself in the brain during treatment could lead to better, more effective treatment. In this project, an MRI method will be developed to map the regional distribution of lithium in the brains of bipolar-disorder patients.

描述（由申请人提供）：锂 (Li) 仍然是治疗双相情感障碍（躁狂抑郁症）的支柱。尽管进行了大量研究，但李的作用机制和大脑区域分布尚不清楚。双相情感障碍的症状表明某些大脑区域主要与该疾病有关。例如，在称为前边缘网络的大脑区域中观察到异常。李对双相情感障碍的临床效果很可能来自于它对这些大脑区域的影响，而不是来自于它在整个大脑中的存在。了解Li在大脑内的区域分布将阐明Li的治疗作用机制、神经毒性作用以及患者对药物反应的广泛差异。它将决定李在关键大脑区域是否达到足够的浓度。磁共振成像（MRI）是一种强大的临床诊断工具。在标准临床 MRI 中，图像对比度主要由组织水中氢 (1H) 的各种 MRI 信号参数的差异提供。可以从 1H 以外的元素（例如 7Li）生成 MRI 信号，以提供该元素在大脑中的图谱。对于 7Li MRI，早期尝试绘制接受 Li 治疗的患者大脑中 Li 的空间分布图，但没有成功。治疗期间大脑中Li浓度较低（~1 mM）、7Li相对于1H的敏感性较低以及很长的自旋晶格弛豫时间（T1）使得7Li MRI过于不敏感而无法提供可用信息。现在，这些问题可以通过更高磁场扫描仪的灵敏度提高、改进的电子设备和新的 MRI 脉冲序列来克服，以减少长 T1 的影响。我们将在辛辛那提大学医学院影像研究中心的 4-T MRI 研究扫描仪上开发和实施体内 7Li MRI。该提案的具体目标是：1）比较测试样本中的标准梯度回波、小顶角MRI序列、自旋回波、大顶角MRI序列和短回波时间驱动平衡傅里叶变换MRI序列，以确定体内7Li MRI测量的最佳序列； 2) 使用特定目标 1 中的最佳 7Li MRI 方法，测量 10 名接受 Li 治疗双相情感障碍的患者在稳态时大脑中 Li 的分布，作为该方法有效性的测试。公众健康相关性：锂是双相情感障碍的重要治疗方法，双相情感障碍是一种毁灭性的精神疾病，约 3% 的人口患有这种疾病。了解治疗期间锂如何在大脑中分布可以带来更好、更有效的治疗。在该项目中，将开发一种 MRI 方法来绘制双相情感障碍患者大脑中锂的区域分布图。