Magnetic resonance imaging of lithium in human brain

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）的主要药物。尽管有大量的研究，李的作用机制和脑中的区域分布是未知的。双相情感障碍的症状表明，某些大脑区域主要涉及疾病。例如，在被称为前边缘网络的大脑区域中观察到异常。很可能李的临床效果在双相情感障碍产生的影响，在这些大脑区域，而不是从它的存在，在大脑的整体。了解Li在大脑中的区域分布将澄清Li的治疗作用，神经毒性作用以及患者对药物反应性的广泛差异的机制。它将决定锂是否在关键的大脑区域达到足够的浓度。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，图像对比度主要由来自组织水中的氢（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7 Li）生成MRI信号，以提供该元素在大脑中的映射。对于7 Li MRI，绘制Li治疗患者脑中Li空间分布的早期尝试不成功。治疗期间大脑中Li的浓度较低（约1 mM），7 Li相对于1H的灵敏度较低，以及非常长的自旋-晶格弛豫时间（T1）使得7 Li MRI太不敏感，无法提供有用的信息。现在，这些问题可以通过高磁场扫描仪、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成像研究中心的4-T MRI研究扫描仪上开发和实施体内7 Li MRI。本提案的具体目的是：1）在测试样本中比较标准梯度回波、低顶角MRI序列、自旋回波、大顶角MRI序列和短回波时间驱动平衡傅立叶变换MRI序列，以确定用于体内7 Li MRI测量的最佳序列;（2）使用特定目标1中的最佳7 Li MRI方法，测量10名正在用Li治疗双相情感障碍的患者的脑中Li的分布，并在稳态下作为该方法的有效性的测试。公共卫生相关性：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，约占人口的3%。了解锂在治疗过程中如何在大脑中分布可能会导致更好，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。

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.