Advanced Optical Image Probe for Neurophysiology

描述（由申请人提供）：大多数人类心理功能诊断测试的核心是一种成像技术，可以将整个大脑的活动模式可视化。在不久的将来，我们可以想象一种检查台的发展，它可以用电磁波无创地浸泡病人，扫描结构和功能，并创建三维（3D）图像或电影。许多这样的成像技术是可用的，包括PET， MRI， MEG， EEG和光学技术，它们提供了独特的补充和显着的优势。大多数光学方法可视化相对缓慢的过程，如伴随神经组织代谢激活的血流量、体积和氧合的变化。与代谢和血流动力学过程相关的光吸收变化是稳健的，相对容易获得无创的，但空间和时间分辨率受到脑灌注的解剖和生理调节的限制。我们观察到大鼠体感觉皮层的快速光学变化与诱发电反应和伴随诱发反应的快速振荡（200- 600hz）直接相关。与噪声相比，这种体内信号很小，通常需要1000到4000个平均值，并且妨碍了神经激活的动态研究。我们的主要目的是研究快速光信号的生物物理机制，提高哺乳动物神经组织的信噪比。为实现这一目标，我们将追求三个具体目标。首先，我们将测试一个假设，即共聚焦双折射照明将增强更快的光信号，而不是传统上用亮场照明看到的较慢的血流动力学成分。我们的第二个目标是验证快速光学信号的早期成分将专门定位于皮质柱的假设。在我们的第三个目标中，我们将测试双折射信号源于细胞膨胀引起的折射率变化的假设，并将遵循电压敏感染料和膜电位。在过去的三年中，我们已经显著提高了光学测量记录快速神经生理事件的效用。这些新目标的实现对于将光学技术推向更实际的应用至关重要，这些应用可以用更好的信噪比成像神经活动的电相关。

DESCRIPTION (provided by applicant): At the center of most diagnostic tests for human mental function is an imaging technique that visualizes activity patterns across the brain. In the near future, we can imagine the development of an examination table which non-invasively bathes the patient with electromagnetic waves, scanning for both structure and function, and creating three dimensional (3D) images or movies. Many such imaging techniques are available, including PET, MRI, MEG, EEG and optical techniques which offer a unique complement and significant advantages. Most optical methods visualize comparatively slow processes such as the changes in blood flow, volume and oxygenation that accompany metabolic activation of neural tissue. Changes in light absorbance associated with metabolic and hemodynamic processes are robust and relatively easy to obtain non-invasively, but spatial and temporal resolution is limited by the anatomy and physiological regulation of cerebral perfusion. We have observed very fast optical changes in rat somatosensory cortex that are directly related to the evoked electrical response and to a fast (200-600 Hz) oscillation that accompanies the evoked response. Such in-vivo signals are small compared to noise, often requiring 1000 to 4000 averages, and preclude dynamic studies of neural activation. Our principal aim is to investigate the biophysical mechanisms of fast optical signals and to improve the signal-to-noise ratio in mammalian neural tissue. To accomplish this aim we will pursue 3 specific aims. First, we will test the hypothesis that confocal birefringence illumination will enhance the faster optical signals over the slower hemodynamic components traditionally seen with bright-field illumination. Our second aim will test the hypothesis that the early components of the fast optical signals will localize specifically to the cortical column. Within our third aim, we will test the hypothesis that birefringence signals originate from a change in refractive index due to cellular swelling and will follow voltage sensitive dye and membrane potentials. Over the past 3 years we have significantly improved the utility of optical measurements for recording fast neurophysiological events. Accomplishment of these new goals is crucial to moving optical techniques into more practical applications that image electrical correlates of neural activity with better signal-to-noise.