Optical Tomography of Intrinsic Signals in Rat Cortex

描述（由申请人提供）：血流动力学活动在脑功能和疾病中起重要作用。人们对大脑中神经元和血管活动之间的联系知之甚少。这在一定程度上源于缺乏定量方法来定位血流动力学的三维变化，并具有足够的时间和空间分辨率来监测血流动力学对刺激反应的进展。内禀信号光学成像（ISOI）是一种基于相机的皮质活动成像方法。通过测量从被照亮的大脑发出的光强度的变化，ISOI允许研究人员对伴随神经元活动的血流动力学变化进行成像。由于ISOI能够以高空间和时间分辨率成像大的皮质区域，因此它已成为研究皮质功能结构和可塑性的重要工具。然而，ISOI有两个主要的局限性，阻碍了我们破译血流动力学和神经元活动之间复杂关系的能力。首先，通常很难确定所测信号是由于血红蛋白浓度的变化还是血红蛋白氧合状态的改变。其次，ISOI仅提供二维图像，无法深入定位血流动力学活动。我们最近使用多光谱ISOI获得了初步结果，证明了在须刺激期间大鼠皮层血流动力学活动的层析定位。这是可能的，因为近红外光比可见光更能穿透大脑。通过使用跨越可见光和近红外（NIR）的许多波长的光，并应用层析成像方法，我们成功地形成了大鼠体感觉皮层血流动力学活动的三维层析图像。此外，我们还能够通过使用空间频域成像（SFDI）技术结合多光谱图像分析来量化血红蛋白浓度和氧合状态的动态变化。R21提案的目的是验证和完善这一令人兴奋的新发现。在两年的资助期内，我们将把快照高光谱成像纳入我们已建立的光学脑成像方法- ISOI和SFDI。我们将优化我们的断层图像重建方法，使其在大鼠皮层中使用动态组织模拟幻象，并使用我们建立的协议在成年大鼠中验证我们的方法。

DESCRIPTION (provided by applicant): Hemodynamic activity plays an important role in brain function and disease. The connection between neuronal and vascular activity in the brain is poorly understood. This in part stems from the lack of quantitative methods to localize hemodynamic changes in three-dimensions with sufficient temporal and spatial resolution to monitor the progression of the hemodynamic response to a stimulus. Intrinsic Signal Optical Imaging (ISOI) is a camera-based method for imaging cortical activity. ISOI allows researchers to image the hemodynamic changes that accompany neuronal activity by measuring changes in intensity of light remitted from an illuminated brain. Because it is capable of imaging large cortical regions with high spatial and temporal resolution, ISOI has become an important tool for studying the functional architecture and plasticity of the cortex. However, ISOI has two major limitations that have hampered our ability to decipher the complex relationship between hemodynamics and neuronal activity. First, it is often difficult to determine whether measured signals are due to changes in hemoglobin concentration or alterations in hemoglobin oxygenation state. Second, ISOI only provides two-dimensional images, and thus cannot localize hemodynamic activity in depth. We have recently acquired preliminary results using multi-spectral ISOI that demonstrate tomographic localization of hemodynamic activity in rat cortex during whisker stimulation. This is possible because near- infrared light penetrates much more deeply into the brain than visible light. By using many wavelengths of light spanning both the visible and near-infrared (NIR), and applying tomographic imaging methods, we have succeeded in forming three-dimensional tomographic images of hemodynamic activity in the rat somatosensory cortex. In addition, we have also been able to quantify dynamic changes in hemoglobin concentration and oxygenation state by employing spatial frequency domain imaging (SFDI) techniques in conjunction with multi-spectral image analysis. The purpose of this R21 proposal is to validate and refine this exciting new finding. Over the course of the two year funding period, we will incorporate snapshot hyperspectral imaging into our established optical brain imaging methods - ISOI and SFDI. We will optimize our tomographic image reconstruction methods to work in the rat cortex using dynamic tissue simulating phantoms, and validate our approach using our established protocol for whisker stimulation in the adult rat. PUBLIC HEALTH RELEVANCE: Deciphering the connection between hemodynamic and neuronal activity is crucial for advancing our understanding of normal brain function, gaining insight into brain pathologies, and developing more effective neuro-therapies. However, current brain functional imaging methods are limited in their ability to localize and quantify hemodynamic activity in the brain. The goal of this work is to develop and validate a new technique based on principles of hyperspectral spatial frequency domain imaging to meet this need for high- resolution three-dimensional functional tomography of cerebral hemodynamics.