Advanced Optical Image Probe for Neurophysiology

描述(由申请人提供)：在大多数人类精神功能诊断测试的中心是一种成像技术，它可以可视化整个大脑的活动模式。在不久的将来，我们可以想象开发出一种检查台，它可以非侵入性地让患者沐浴在电磁波中，扫描结构和功能，并创建三维(3D)图像或电影。有许多这样的成像技术可用，包括PET、MRI、MEG、EEG和光学技术，它们提供了独特的补充和显著的优势。大多数光学方法显示相对缓慢的过程，如伴随着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，相对容易非侵入性获得，但空间和时间分辨率受限于脑血流的解剖和生理调节。我们观察到大鼠躯体感觉皮层的快速光学变化与诱发的电反应直接相关，并与伴随诱发反应的快速(200-600赫兹)振荡有关。这样的体内信号与噪声相比很小，通常需要1000到4000个平均值，并且排除了对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，并提高哺乳动物神经组织的信噪比。为了实现这一目标，我们将追求3个具体目标。首先，我们将测试一个假设，即共焦双折射照明将增强较快的光信号，而不是传统的明场照明所看到的较慢的血流动力学分量。我们的第二个目标将检验这样的假设，即快速光信号的早期分量将特定地定位于皮质柱。在我们的第三个目标中，我们将测试双折射信号起源于细胞膨胀引起的折射率变化的假设，并将跟随电压敏感染料和膜电位。在过去的三年里，我们已经显著提高了光学测量在记录快速神经生理事件方面的效用。这些新目标的实现对于将光学技术转化为更实际的应用至关重要，这些应用可以使神经活动的电学关联与更好的信噪比相关联。

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.