Direct functional imaging of electrical brain stimulation

描述（由申请人提供）：功能性神经成像的直接方法对于理解神经行为，可塑性，连通性和病理学的进步至关重要。如果我们能直接成像活跃的神经元，我们将有能力比目前的功能磁共振成像更精确地检查神经活动。我们已经开发了一种基于核磁共振的电导率成像技术，磁共振电阻抗断层扫描（MREIT），可以重建电导率图与近核磁共振分辨率。在MREIT中，小的外部电流被施加到一个物体上。由电流产生的磁流变磁通密度模式可转换为电导率或电流密度切片图像。我们开发了这项技术，并将其改进到使用相对较低的电流在体内产生动物大脑电导率图像的阶段。在活动期间发生的膜电导的巨大变化引起外部施加电流所采取的路径的动态变化。外部电流施加期间尖峰活动的变化将导致MR数据中的差相积累，这将增加施加较长的电流。因此，神经活动随着与活跃的细胞内区域相一致的体素的表观电导率的增加而变得可见。由于对比控制MREIT信号，电导率，可能只获得正值，相位积累不能被相反极性或相反定向信号的存在所抵消。与其他基于核磁共振成像的神经电流成像方法相比，这可能使MREIT具有优势，这些方法主要基于由轴突电流总和引起的相位或主磁场扰动。因此，MREIT具有检测包括灰质在内的复杂结构活动的潜力。在这个提议中，我们将研究功能性MREIT （fMREIT）检测神经组织中与活动相关的电导率变化的能力。我们将开发fMREIT技术来成像体外的神经活动，在几种标准的神经制剂中，同时逐步完善我们的方法来检测和定位高信噪比的活性细胞

DESCRIPTION (provided by applicant): Direct methods for functional neural imaging are critical to advancements in understanding neural behavior, plasticity, connectivity and pathology. If we can directly image active neurons we will have the ability to examine neural activity more precisely than is presently the case with fMRI. We have developed an MRI-based conductivity imaging technique, Magnetic Resonance Electrical Impedance Tomography (MREIT) that can reconstruct conductivity maps with near-MRI resolution. In MREIT, small external currents are applied to an object. The MR magnetic flux density patterns created by current flow may be converted to conductivity or current density slice images. We developed this technique and have refined it to the stage of producing electrical conductivity images of animal brains in vivo, using relatively low applied currents. The large changes in membrane conductance that occur during activity cause dynamic changes in paths taken by externally applied currents. Changes in spiking activity during external current application will cause differential phase accumulation in MR data that will increase the longer current is applied. Neural activity therefore becomes visible as an increase in apparent conductivities of voxels coincident with active intracellular areas. Because the contrast controlling MREIT signals, conductivity, may only acquire positive values, phase accumulations cannot be cancelled by the presence of opposite polarity or opposingly oriented signals. This may give MREIT an advantage compared with other MRI-based methods for imaging neural currents that are based on perturbations of phase or main magnetic fields caused principally by summed axonal current flows. Thus, MREIT has the potential to detect activity in complex structures including gray matter. In this proposal, we will investigate the ability of functional MREIT (fMREIT) to detect activity-related conductivity changes in neural tissue. We will develop fMREIT techniques to image neural activity in vitro, in a several standard neural preparations, while progressively refining our methods to detect and locate active cells at high signal to noise ratio and using main magnetic field strengths conveniently used in vivo. In isolated preparations, our method has the potential to enable detailed analyses of single cell mechanisms. The method could thus be considered as a non-invasive extension of patch clamping techniques, and could stand alone for this purpose. However, ultimately we wish to image activity in vivo and our final study in this program will include a tentative exploration of fMREIT in a live animal model as a precursor to further research in this area. In summary, this study will establish the basis for functional MREIT (fMREIT) techniques. This method could ultimately be used to visualize effects of more general neural behavior and enable more fundamental analyses of neural behavior in vivo than is available with existing techniques such as fMRI.