Computational Optical Tomography for Anti-stroke Therapy (R21/R33)

描述（由申请人提供）：漫射光学层析成像（DOT）和CCD技术的最新发展可以使我们获得高质量、高分辨率的光学层析成像图像，对于这些图像，不可避免地需要先进的三维（3D）成像重建算法。本建议的目的是开发一种快速的全局收敛重建（GCR）算法，通过结合DOT，CGD测量和近红外光谱（NIRS）获得血管氧合的三维断层成像。有了这样一个上级重建算法，它具有处理大数据集的能力，并在数学上被证明是收敛在任何复杂的背景下，我们将能够完成3D，非侵入性的光学成像作为一种动态监测手段，调查缺血性中风期间使用动物模型的微循环功能障碍。R21阶段的具体目标是：（1）设计并实现一种基于CCD相机的NIRS成像系统，适用于脑氧合血红蛋白（HbO）和总血红蛋白（HbT）浓度的动态成像;（2）开发并验证基于CCD/NIR测量的血管内容物和氧合的3D断层重建快速GCR算法。R21初始开发成功后，PI及其合作者将使用动物模型将开发的GCR算法应用于缺血性卒中期间微循环功能障碍的研究。R33阶段的具体目标是：（1）使用具有CCD/NIR测量的开发的GCR算法来获得缺血性中风期间和之后的大鼠体内的脑氧合血红蛋白浓度、总血红蛋白和光散射参数的3D断层图像，（2）表征通过3D NIR成像鉴定的脑缺血诱导的微血管功能障碍，（3）确定抗中风药物对脑缺血模型中微血管功能障碍的影响，以及（4）为学术和医学团体中的用户实现集成的、用户友好的平台/环境，以共享（a）我们开发的用于NIR断层摄影成像的3D GCR算法和（B）我们的数据密集型、基于CCD相机的NIR光谱读数。经验证后，该技术可用于其他类型的神经系统疾病和治疗监测。此外，这种功能成像技术将提高我们对缺血性卒中的动力学、机制和异质性的理解。

DESCRIPTION (provided by applicant): Recent development in diffuse optical tomography (DOT) and CCD technology may allow us to achieve high-quality, good-resolution, optical tomographic images, for which advanced 3-dimensional (3D) imaging reconstruction algorithms are inevitably needed. The objective of this proposal is to develop a fast globally convergent reconstruction (GCR) algorithm for 3D tomographic imaging of vascular oxygenation obtained by combining DOT, CGD measurements, and the near infrared spectroscopy (NIRS). With such a superior reconstruction algorithm, which has a capability to handle large data sets and proven mathematically to be of convergence at any complex background, we will be able to accomplish 3D, non-invasive optical imaging as a dynamic monitoring means to investigate microcirculatory dysfunction during ischemic stroke using animal models. The specific aims in the R21 phase are (1) to design and implement a CCD-camera-based, NIRS imaging system suitable for dynamic imaging of cerebral concentrations of oxygenated hemoglobin (HbO) and total hemoglobin (HbT), and (2) to develop and to validate the fast GCR algorithm for 3D tomographic reconstruction of vascular contents and oxygenation based on the CCD/NIR measurements. After success of the initial R21 development, the PI and her collaborators will apply the developed GCR algorithm to the investigation of microcirculatory dysfunction during ischemic stroke using animal models. The specific aims in the R33 phase are: (1) using the developed GCR algorithm with the CCD/NIR measurements to obtain 3D tomographic images of cerebral concentrations of oxygenated hemoglobin, total hemoglobin, and light scattering parameters from the rats in vivo during and after ischemic stroke, (2) to characterize the cerebral-ischemia- induced microvasculature dysfunction identified by the 3D NIR imaging, (3) to determine the effect of a anti- stroke drug on microvasculature dysfunction in the cerebral ischemia model, and (4) to implement an integrated, user-friendly platform/environment for users in academic and medical communities for sharing both (a) our developed 3D GCR algorithm for NIR tomographic imaging and (b) our data-intensive, CCD camera based, NIR spectroscopic readings. The proposed technique and development can be readily applicable to other types of neurological deceases and therapeutic monitoring after its validation. Furthermore, this functional imaging technique will enhance our understanding on dynamics, mechanism, and heterogeneity of ischemic stroke.