Direct functional imaging of electrical brain stimulation

描述（由申请人提供）：功能神经成像的直接方法对于理解神经行为、可塑性、连接性和病理学的进步至关重要。如果我们能直接对活跃的神经元成像，我们就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MRI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MRI的分辨率。在MREIT中，小的外部电流被施加到对象。由电流产生的MR磁通量密度模式可以被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外加电流在体内产生动物大脑的电导率图像的阶段。在活动期间发生的膜电导的大的变化引起外部施加的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数据中的差分相位累积，这将增加施加的电流的时间。因此，神经活动变得可见，因为与活跃的细胞内区域一致的体素的表观电导率增加。因为对比度控制MREIT信号，电导率，可能只获得正值，相位累积不能被相反极性或相反取向的信号的存在所抵消。与其他基于MRI的神经电流成像方法相比，这可能使MREIT具有优势，这些方法基于主要由总和轴突电流引起的相位或主磁场的扰动。因此，MREIT有可能检测包括灰质在内的复杂结构的活动。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，在几种标准神经制备物中对体外神经活动进行成像，同时逐步完善我们的方法，以高信噪比检测和定位活性细胞，并使用主要的 在体内方便使用的磁场强度。在分离的制剂中，我们的方法有可能使单细胞机制的详细分析。因此，该方法可以被认为是膜片钳技术的非侵入性延伸，并且可以单独用于此目的。然而，最终我们希望在体内成像活动，我们在这个项目中的最终研究将包括在活体动物模型中对fMREIT的初步探索，作为这一领域进一步研究的先驱。综上所述，本研究将为功能性MREIT奠定基础 （fMREIT）技术。这种方法最终可以用来可视化更一般的神经行为的影响，并使更多的神经行为在体内的基础分析比现有的技术，如功能磁共振成像。

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.