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

描述(申请人提供)：漫反射光学层析成像(DOT)和CCD技术的最新发展可能使我们能够获得高质量、高分辨率的光学层析图像，为此不可避免地需要先进的三维(3D)成像重建算法。该方案的目的是开发一种快速的全局收敛重建(GCR)算法，用于结合DOT、CGD测量和近红外光谱(NIRS)获得的血管氧合三维断层成像。有了这样一种优越的重建算法，它具有处理大数据集的能力，并且在数学上被证明在任何复杂的背景下都是收敛的，我们将能够完成3D、非侵入性光学成像，作为一种动态监测手段，使用动物模型来研究缺血性中风期间的微循环功能障碍。R21阶段的具体目标是：(1)设计和实现一个基于CCD摄像机的近红外成像系统，适用于动态成像脑氧合血红蛋白(HBO)和总血红蛋白(HBT)浓度；(2)开发和验证基于CCD/NIR测量的用于血管内容物和氧合三维重建的快速GCR算法。在最初的R21开发成功后，PI和她的合作者将使用动物模型将开发的GCR算法应用于缺血性中风期间微循环功能障碍的研究。R33阶段的具体目标是：(1)使用开发的GCR算法与CCD/NIR测量相结合，获得缺血期和卒中后在体大鼠脑内氧合血红蛋白、总血红蛋白和光散射参数的3D断层图像，(2)通过3D NIR成像确定脑缺血诱导的微血管功能障碍的特征，(3)在脑缺血模型中确定抗中风药物对微血管功能障碍的影响，以及(4)实施一种综合的、为学术和医学领域的用户提供用户友好的平台/环境，用于共享(A)我们开发的用于近红外断层成像的3D GCR算法和(B)我们基于CCD相机的数据密集型近红外光谱读数。所提出的技术和发展可以很容易地适用于其他类型的神经系统疾病和治疗监测后，其验证。此外，这种功能成像技术将加深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.