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

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）技术直接成像人脑中神经元电流的可行性。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信号的可测量变化，可以在ULF用现有的磁共振成像（MRI）技术成像。该提案是对RFA-EB-05-001：“神经活动成像的新方法”的回应。“MRI对感兴趣的体积中的核（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，以产生精美的解剖特征。在过去的十年中，测量血液动力学反应的功能性MRI（fMRI）研究也出现了爆炸式增长;然而，正如本RFA所指出的，此类反应相对缓慢，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。虽然这些模态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推断。因此，MEG和EEG中的电生理“成像”充其量只是“间接”的。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，例如引起相位和振幅变化或改变NMR信号的衰减速率。组织中神经元电流和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HF DNI的可行性上。最近，我们的团队（和其他一些人）已经实验性地展示了超低场（ULF）MRI，使用比HF-MRI弱100，000 - 1，000，000倍的场。虽然在ULF下的NMR信号（称为自由感应衰减（FID））显著弱于HF，但是我们使用超导量子干涉装置（SQUID）技术获得了在ULF下的FID的高信噪比测量。我们最近还提出了世界上第一个同时FID和MEG测量人脑，使用SQUID传感器。我们的研究将使用两种不同的方法来证明在ULF处测量神经元电流对NMR签名的影响的可行性：1）我们将研究神经元电流与组织中的质子自旋群体之间的相互作用，其诱导自旋群体的退相;和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，这种机制将导致神经元电流的明显不同的弛豫。spin人口。第一种方法是在高场DNI提出的想法的直接扩展，但可以在ULF中大大增强。我们的第二种方法追求ULF独有的令人兴奋的可能性。

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.