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下使用核磁共振技术直接成像人脑中的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，导致核磁共振信号发生可测量的变化，这可以在ULF使用现有的磁共振成像(MRI)技术进行成像。这项提议是对RFA-EB-05-001：“成像神经活动的新方法”的回应。核磁共振在空间上编码了感兴趣体积中的原子核，通常是质子的核磁共振签名。今天的高场(HF)核磁共振机器使用1.5T到9T以上范围的静态磁场来产生精致的解剖特征。在过去的十年里，也见证了测量血液动力学反应的功能磁共振(FMRI)研究的爆炸性增长；然而，正如本RFA所指出的，这种反应相对缓慢，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。虽然这些模式产生了详细的时间信息，但空间定位必须从高精度的空间建模先验推断出来。因此，脑磁图和脑电波的电生理“成像”充其量只能是“间接”的。最近，一些研究人员提出，电生理活动可能以一种可测量的方式与核自旋相互作用，例如引起核磁共振信号的相位和幅度变化或改变核磁共振信号的衰减率。组织中神经元电流和自旋群体之间的相互作用可能使MRI直接进行神经元成像(DNI)。到目前为止，大多数研究都集中在高频下DNI的可行性上。最近，我们小组(和其他几个小组)已经在实验中展示了超低场MRI，使用的磁场比HF-MRI弱100,000-1,000,000倍。虽然在ULF的核磁共振信号(称为自由感应衰变(FID))比HF弱得多，但我们使用超导量子干涉装置(SQUID)技术获得了在ULF对FID的高信噪比测量。我们最近还展示了世界上第一个使用鱿鱼传感器同时测量人脑FID和MEG的方法。我们的研究将继续论证使用两种不同的方法测量神经元电流对ULF核磁共振特征的影响的可行性：1)我们将研究神经元电流和组织中质子自旋布居之间的相互作用，导致自旋布居的退相；2)我们将研究一种基于神经元电流和自旋布居的相互作用的新机制，这将导致自旋布居的明显不同的驰豫。第一种方法是在高场下对DNI提出的想法的直接延伸，但在ULF可以大大增强。我们的第二种方法追求一种令人兴奋的可能性，这是乌尔夫独有的。

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.