In vivo imaging of therapeutic electric current flow

描述（由申请人提供）：经颅直流电刺激（tDCS）和脑深部电刺激（DBS）是电刺激疗法的例子，作为调节运动功能、语义处理和执行功能的手段，它们正迅速获得关注。这两种疗法都吸引了许多临床和实验研究。tDCS对大脑有促进和抑制作用，这取决于刺激极性和电极位置。DBS在治疗运动障碍（主要是帕金森氏病）方面已得到全面的临床评估，并正在扩大其治疗范围，包括局灶性肌张力障碍、抑郁症和慢性疼痛等疾病。虽然大部分仍处于实验阶段，但tDCS的应用和接受度正在迅速增长。尽管与tDCS相关的功能改变可以在不了解潜在神经生理学的情况下进行分类，但了解任何电刺激技术中外部施加电流的实际流向是至关重要的，因为这是了解哪些大脑区域、回路或元素受到这些治疗的影响以及这些变化如何发生的基础。这些知识将有助于更好地理解这些疗法的机制，从而找到更集中、更有效的刺激模式和位置。最终，这将导致更有效和新颖的临床应用。许多研究使用计算机模拟模拟了当前应用在颅外和颅内模式下的效果。模拟总是受到分割过程中解释MRI数据的错误，假设和实际电导率值之间的差异以及实际和假设电极位置和尺寸之间的不匹配的限制。因此，迫切需要更好的方法来理解和验证电流分布。在本提案中，我们将使用最近开发的基于核磁共振成像的相位成像技术来更直接地测量体内电流密度。与早期基于核磁共振的测量电流的方法不同，我们的技术不需要受试者重新定位。我们的方法将在包含许多组织区室的高分辨率主题特定模型中得到验证，包括各向异性白质。因此，我们将把我们新的直接测量方法与最先进的建模方法进行比较。

DESCRIPTION (provided by applicant): Transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) are examples of electrical stimulation therapies that are rapidly gaining attention as means of modulating motor function, semantic processing, and executive function. Both therapies have attracted many clinical and experimental studies. tDCS has been found to have both facilitatory and inhibitory effects on the brain depending on stimulation polarity and electrode position. DBS has been thoroughly evaluated clinically for treatment of movement disorders, principally Parkinson's disease, and is extending its reach to include treatment of disorders such as focal dystonia, depression and chronic pain. While still mostly in the experimental stage, tDCS applications and acceptance are growing extremely rapidly. Although the functional alterations associated with tDCS can be categorized without knowledge of the underlying neurophysiology, an understanding of where externally applied current actually flows in any electrical stimulation technique is crucial as a basis for understanding which brain regions, circuits, or elements are affected by these therapies, and how these changes may occur. Such knowledge will lead to a better understanding of the mechanisms underlying these therapies, and thus to more focused and effective stimulation patterns and locations. Ultimately, this will lead to more efficient and novel clinical applications. Many studies have simulated the effects of current application in both extra- and intracranial modalities using computer simulation. Simulations will always be limited by errors in interpreting MRI data during segmentation, differences between assumed and actual electrical conductivity values, and mismatches between actual and presumed electrode locations and sizes. Thus, better methods to understand and verify current flow distributions are badly needed. In this proposal we will use a recently developed MRI-based phase imaging technique to more directly measure current densities in vivo. Unlike earlier MR-based methods of measuring electrical current flow, our technique works without requiring subject repositioning. Our methods will be validated against high-resolution subject-specific models incorporating many tissue compartments, including anisotropic white matter. Thus, we will compare our new direct measurement method against state-of-the-art modeling approaches.