PROTON TRANSFER IMAGING OF GLYCINE IN THE SPINAL CORD

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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， 局部环境，如pH值和血流。 甘氨酸是一种神经递质， 中枢神经系统中重要的抑制性神经递质。甘氨酸依赖性突触 被发现高度集中在脑干、视网膜和脊髓。的存在和 甘氨酸受体的位置表明，甘氨酸信号可能是神经细胞中的关键角色， 许多运动和认知疾病的病理学;一些显著的例子包括肌萎缩性 侧索硬化症（ALS）、帕金森病、过度兴奋和阵发性运动。 这些因素的侵入性测量是困难的，可能会造成更多的伤害，病人比 效益虽然磁共振波谱（MRS）先前已经用于测量 中枢神经系统（CNS）中的神经递质浓度，该技术缺乏 在常规临床研究中使用足够的空间分辨率。测量这种能力 在高分辨率的非侵入性方面将是诊断的一个重大突破， 这些和许多其他疾病。蛋白质不稳定质子与水的化学交换 质子可以使磁共振成像（MRI），主要用于检测散装 水信号，对内源性蛋白质浓度及其 环境.最近，一种称为化学交换依赖饱和转移的技术 （CEST），其使用通过磁化交换的大量水磁化的衰减 与饱和不稳定质子，已被用来表征稀不稳定基团的性质。而 CEST研究已经探索了许多代谢物，但还没有研究证明 甘氨酸中的CEST效应。旋转坐标系（T1 <$）中的自旋-晶格弛豫是另一个对比 这是一种依赖于化学交换的技术。 迄今为止，还没有研究使用T1 <$作为质子化学交换的对比。 化学交换效应随静磁场呈二次方变化。因此，T1？ 在探测交换介导的相互作用中， 核自旋系统 T1 ~ MRI的这种更高的灵敏度可以检测代谢物， 脑中的浓度非常低（约1 mM）。 我们假设，这是可能的，以量化甘氨酸在更高的磁场CEST效应 （e3T）。此外，T1 <$MR成像对质子化学交换的敏感性高于 超高静磁场下的CEST方法。最后，我们认为，测定甘氨酸是可行的 in vivo体内in the spinal脊髓cord脊髓. 这些假设将通过完成以下具体任务进行检验 目的： 目标一： 为了在体外生理条件下测量甘氨酸的化学位移， CEST成像。 目标二： 确定浓度、pH值、静磁场、B1场强 和饱和时间对甘氨酸化学交换的影响。 目标3： 为了证明，在不同的静磁场强度下， 甘氨酸可以在T1上提供对比度，加权图像，并在超高静态场显示， 比CEST效应更敏感。 目标4： 为了使用CEST在大鼠模型中非侵入性地体内测量甘氨酸浓度， T1？加权图像

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.