Direct Imaging of Neural Currents using Ultra-Low Field Magnetic Resonance Techni

使用超低场磁共振技术直接成像神经电流

• 批准号: 7139534
• 负责人: John Compton Mosher
• 金额: $ 45.9万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-11 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7139534
• 关键词: brain; clinical research; human; hydrogen ions; magnetic field; magnetism; measurement; model; motivation; relaxation; sectioning; tissues

DESCRIPTION (provided by applicant): We propose to demonstrate the feasibility of using nuclear magnetic resonance (NMR) techniques at ultra- low fields (ULF) to directly image neuronal currents in the human brain. We hypothesize that neuronal currents (both intra- and extra-cellular) will interact with the proton spins in tissue resulting in a measurable change in the NMR signal that can be imaged with existing magnetic resonance imaging (MRI) techniques at ULF. This proposal is in response to RFA-EB-05-001: "New Ways to Image Neural Activity." MRI spatially encodes the NMR signature of nuclei, typically protons, in a volume of interest. Today's high-field (HF) MRI machines employ static magnetic fields in the 1.5 T to above 9 T range to yield exquisite anatomical features. The last decade has also witnessed an explosion in functional MRI (fMRI) research that measures hemody- namic responses; however, as this RFA notes, such responses are relatively sluggish and only indirectly related to electrophysiological processes. Magnetoencephalography (MEG) and electroencephalography (EEG) are direct measures of the external magnetic and electric fields generated by neuronal currents. While these modalities yield detailed temporal information, the spatial localization must be inferred from highly-spe-cific spatial modeling priors. The electrophysiological "imaging" in MEG and EEG is therefore only "indirect" at best. Recently, several researchers proposed that electrophysiological.activity may interact with the nuclear spins in a measurable manner, such as causing phase and amplitude variations or changing the rate of decay in the NMR signal. Interactions between neuronal currents and spin populations in tissue may enable direct neuronal imaging (DNI) by MRI. Most studies to date have focussed on the feasibility of DNI at HF. Recently, our group (and a few others) has experimentally demonstrated ultra-low field (ULF) MRI, using fields 100,000- 1,000,000 times weaker than HF-MRI. While the NMR signals, known as the free induction decay (FID), at ULF are dramatically weaker than HF, we acquired high signal-to-noise measurements of FIDs at ULF using super- conducting .quantum interference device (SQUID) technology. We also recently presented the world's first simultaneous FID and MEG measurement of the human brain, using SQUID sensors. Our research will pursue demonstrating the feasibility of measuring a neuronal current effect on the NMR signature at ULF using two distinct approaches: 1) we will study interactions between neuronal currents and the proton spin population in tissue that induce dephasing of the spin population; and 2) we will study a novel mechanism based on the interaction of neuronal currents and the spin population that will cause a distinctly different relaxation of the spin population. The first approach is a direct extension of ideas presented for DNI at high fields, but can be greatly enhanced at ULF. Our second approach pursues an exciting possibility unique to ULF.

描述（由申请人提供）： 我们建议证明在超低场（ULF）下使用核磁共振（NMR）技术直接对人脑中的神经元电流进行成像的可行性。我们假设神经元电流（细胞内和细胞外）将与组织中的质子自旋相互作用，导致 NMR 信号发生可测量的变化，可以使用现有的超低频磁共振成像 (MRI) 技术对其进行成像。该提案是对 RFA-EB-05-001：“神经活动成像新方法”的回应。 MRI 对感兴趣体积中的核（通常是质子）的 NMR 特征进行空间编码。当今的高场 (HF) MRI 机器采用 1.5 T 至 9 T 以上范围的静态磁场来产生精致的解剖特征。过去十年还见证了测量血流动力学反应的功能性 MRI (fMRI) 研究的爆炸式增长。然而，正如该 RFA 指出的那样，这种反应相对缓慢，并且仅与电生理过程间接相关。脑磁图（MEG）和脑电图（EEG）是对神经元电流产生的外部磁场和电场的直接测量。虽然这些模式产生详细的时间信息，但空间定位必须从高度特定的空间建模先验中推断出来。因此，脑磁图和脑电图的电生理“成像”充其量只是“间接”。最近，一些研究人员提出，电生理活动可能以可测量的方式与核自旋相互作用，例如引起相位和幅度变化或改变 NMR 信号的衰减率。神经元电流和组织中自旋群体之间的相互作用可以通过 MRI 实现直接神经元成像 (DNI)。迄今为止，大多数研究都集中在 DNI 在 HF 中的可行性。最近，我们的团队（以及其他一些团队）通过实验证明了超低场 (ULF) MRI，其使用的场强比 HF-MRI 弱 100,000-1,000,000 倍。虽然 ULF 下的 NMR 信号（称为自由感应衰变 (FID)）明显弱于 HF，但我们使用超导量子干涉装置 (SQUID) 技术在 ULF 下获得了 FID 的高信噪比测量结果。我们最近还推出了世界上第一个使用 SQUID 传感器对人脑进行 FID 和 MEG 同步测量的技术。我们的研究将致力于证明使用两种不同方法测量神经元电流对 ULF NMR 特征的影响的可行性：1）我们将研究神经元电流与组织中质子自旋群体之间的相互作用，从而引起自旋群体的相移； 2）我们将研究一种基于神经元电流和自旋群体相互作用的新机制，该机制将导致自旋群体明显不同的松弛。第一种方法是在高场上为 DNI 提出的想法的直接扩展，但可以在 ULF 上得到极大的增强。我们的第二种方法追求 ULF 独有的令人兴奋的可能性。