PROTON TRANSFER IMAGING OF GLYCINE IN THE SPINAL CORD

脊髓中甘氨酸的质子转移成像

• 批准号: 8361977
• 负责人: FELIKS KOGAN
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361977
• 关键词: Affect; Amyotrophic Lateral Sclerosis; Blood flow; Brain; Brain Stem; Chemicals; Clinical Research; Cognition Disorders; Detection; Diagnosis; Disease; Environment; Funding; Glycine; Glycine Receptors; Grant; Image; In Vitro; Location; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mediating; Methods; Modeling; Movement; National Center for Research Resources; Neuraxis; Neurotransmitters; Nuclear; Parkinson Disease; Pathologic Processes; Pathology; Patients; Physiological; Principal Investigator; Property; Proteins; Protons; Rattus; Relaxation; Research; Research Infrastructure; Resolution; Resources; Retina; Signal Transduction; Source; Spinal Cord; Synapses; System; Techniques; Testing; Time; United States National Institutes of Health; Water; Weight; attenuation; cost; in vivo; magnetic field; motor disorder; optical imaging; relating to nervous system

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pathologic processes affect the concentrations of certain metabolites or neurotransmitters as well as local surroundings such as pH and blood flow. Glycine is a neurotransmitter that serves as an important inhibitory neurotransmitter in the central nervous system. Glycine-dependent synapses are found to be highly concentrated in the brain stem, retina, and spinal cord. The presence and location of glycine receptors suggest that glycine signaling might be a key player in the neural pathology of many motor and cognitive diseases; some notable examples include Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, hyperekplexia, and paroxysmal movement. Measurement of these factors invasively is difficult and may pose more harm to the patient than benefit. While magnetic resonance spectroscopy (MRS) has previously been used to measure neurotransmitter concentrations in the central nervous system (CNS), this technique lacks the adequate spatial resolution to be used in routine clinical studies. The ability to measure such aspects non-invasively at high resolutions would be a major breakthrough in the diagnoses of these and many other disorders. Chemical exchange between labile protons of proteins and water protons can make Magnetic Resonance Imaging (MRI), utilized mainly for the detection of bulk water signal, sensitive to information about the concentrations of endogenous proteins and their environments. Recently, a technique called Chemical Exchange Dependent Saturation Transfer (CEST), which uses the attenuation of bulk water magnetization through magnetization exchange with saturated labile protons, has been used to characterize properties of dilute labile groups. While CEST studies have explored numerous metabolites, there have been no studies demonstrating the CEST effect in glycine. Spin-lattice relaxation in the rotating frame (T1¿) is another contrast technique that depends on chemical exchange. There have been no studies to date using T1¿ for contrast in the chemical exchange of protons. T1¿ Chemical exchange effects vary quadratically with the static magnetic field. Therefore, T1¿ potentially offer higher sensitivity at higher fields in probing exchange mediated interactions in nuclear spin systems. This higher sensitivity of T1¿ MRI may enable detection of metabolites with very low concentrations (~1 mM) in the brain. We hypothesize that it is possible to quantify the CEST effect in glycine at higher magnetic fields (e3T). Also, that T1¿ MR imaging has higher sensitivity to proton chemical exchange than the CEST method at ultra-high static fields. Finally, we believe that it is feasible to measure glycine in vivo in the spinal cord. These hypotheses will be tested by accomplishing the following specific aims: Aim #1: To measure the chemical shift of glycine in-vitro under physiological conditions using CEST imaging. Aim #2: To determine the effect that concentration, pH, static magnetic field, B1 field strength and saturation time have on the chemical exchange of glycine. Aim #3: To demonstrate, at varying static magnetic field strengths, that the chemical shift of glycine can provide contrast on T1¿weighted images and that at ultra-high static fields it shows greater sensitivity than the CEST effect. Aim #4: To measure glycine concentrations non-invasively in-vivo in rat models using CEST and T1¿weighted images.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 病理过程影响某些代谢物或神经递质的浓度以及 局部环境，如酸碱度和血流量。甘氨酸是一种神经递质，它作为一种 中枢神经系统中重要的抑制性神经递质。甘氨酸依赖突触 被发现高度集中在脑干、视网膜和脊髓。在场和 甘氨酸受体的位置表明甘氨酸信号可能在神经中起关键作用。 许多运动和认知疾病的病理学；一些值得注意的例子包括肌营养不良 侧索硬化症(ALS)、帕金森氏病、多动症和阵发性运动。 对这些因素进行侵入性测量是困难的，并且可能对患者造成比 利益。虽然磁共振波谱(MRS)以前被用来测量 中枢神经系统(CNS)的神经递质浓度，这项技术缺乏 足够的空间分辨率可用于常规临床研究。衡量这一点的能力 在高分辨率下的非侵入性方面将是诊断的一个重大突破 这些和许多其他的障碍。蛋白质不稳定质子与水之间的化学交换 质子可以使核磁共振成像(MRI)主要用于探测块状物质 水分信号，对关于内源蛋白质浓度和它们的信息的敏感 环境。最近，一种名为化学交换依赖饱和转移的技术 (CEST)，它通过磁化交换来衰减散装水的磁化 与饱和的不稳定质子，已被用来表征稀易变基团的性质。而当 CEST研究已经探索了许多代谢物，但还没有研究表明 甘氨酸的CEST效应。旋转标架中的自旋-晶格弛豫是另一个对比 依靠化学交换的技术。 到目前为止，还没有使用T1来对比质子化学交换的研究。 T_1？化学交换效应随静磁场的变化呈二次曲线变化。因此，T1？ 在探测交换介导的相互作用时，可能在更高的领域提供更高的灵敏度 核自旋系统。T1？MRI的这种更高的灵敏度可以使代谢物的检测成为可能 在大脑中的浓度很低(~1 mM)。 我们假设在较高磁场下量化甘氨酸的CEST效应是可能的 (E3T)。此外，T1？MR成像对质子化学交换的敏感度高于 超高静电场下的CEST方法最后，我们认为测定甘氨酸是可行的。 在脊髓的活体内。这些假设将通过完成以下具体任务来检验 目标： 目的#1：测定生理条件下甘氨酸的体外化学位移 CEST成像。 目的#2：测定浓度、pH值、恒磁场、B1场强对 饱和时间对甘氨酸的化学交换有影响。 目标#3：证明在不同的静磁场强度下，化学位移 甘氨酸可以在T1加权图像上提供对比度，在超高静电场下可以显示出对比度 比CEST效应更敏感。 目的#4：用CEST和CEST无创测定大鼠体内甘氨酸浓度 T1？加权图像。