Vascular plasticity in Injured Spinal Cord-Investigations using MRI

描述（由申请人提供）：脊髓损伤（SCI）是一个主要的健康和社会经济问题，影响许多人。磁共振成像（MRI）提供了在体的三维图像与精致的软组织对比研究损伤的脊髓（SC）。在SCI大鼠模型的实验研究中，我们定期使用MRI纵向跟踪同一动物，以便每只动物都可以作为自己的对照。然而，常规MRI对损伤后短暂发生的血管变化提供的信息有限。 需要能够感测血管变化的新型成像方法。作为潜在的成像方法，我们最近探索了磁共振血管造影（MRA）和灌注MRI（P-MRI）技术，用于探测大鼠SC的血管系统。我们的初步数据表明，MRA能够产生高分辨率的大血管投影图，为大鼠SC供血，而P-MRI对脐带组织内的微血管敏感。使用造影剂钆喷酸葡胺（Gd），我们也产生了血管造影，描绘更详细的脊髓血管。在纵向动态对比增强MRI（DCE-MRI）研究中，我们以前量化了损伤后血脊髓屏障（BSCB）通透性的时间变化，并检测了损伤脊髓中的新生血管。基于这些初步结果，我们假设，（解剖MRI、MRA、P-MRI和DCE-MRI）将增加检测损伤SC中的形态学和血管变化的可靠性、灵敏度和特异性。基于MR的测量将提供关于损伤SC的病理学、生理学和功能的非侵入性的有价值的直接信息，并可作为SCI最终神经学结果的预测因子。为了验证这一假设，我们将使用植入式射频线圈在损伤和对照大鼠的SC纵向研究中进行高分辨率体内成像。结合成像，我们还将对从损伤中恢复的动物进行标准神经行为测试，并对损伤的脊髓组织进行定量终点组织学分析。我们将统计学比较基于MR的测量与行为评分和组织学结果，以确定损伤SC的内源性血管可塑性及其在SCI恢复中的作用。无创性确定与SCI后功能恢复相关的SC血管网络重组将是理解恢复机制的一大步，并且从长期来看，客观评估潜在的新疗法，这些新疗法具有操纵SC血管系统的能力，无论是否使用外源性过程来改善神经功能结局。

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) is a major health and socio-economic problem, affecting many individuals. Magnetic resonance imaging (MRI) provides in vivo three-dimensional images with exquisite soft tissue contrast for investigating injured spinal cord (SC). In experimental studies with rat models of SCI, we regularly use MRI to follow the same animal longitudinally, so that each animal can serve as its own control. Conventional MRI, however, provides limited information on vascular changes that occur transiently following the injury. Novel imaging methods with capacity to sense vascular changes are required. As potential imaging approaches, we have recently explored MR angiography (MRA) and perfusion MRI (P- MRI) techniques for probing the vascular system of rat SC. Our preliminary data showed that MRA is capable of producing high-resolution maps of macrovascular projections that supply blood to the rat SC while P-MRI is sensitive to the microvasculature within the cord tissue. Using the contrast agent gadopentate dimeglumine (Gd), we also generated angiograms that delineate the spinal vessels in greater detail. In longitudinal dynamic contrast-enhanced MRI (DCE-MRI) studies, we have previously quantified the temporal changes in permeability of blood-spinal cord barrier (BSCB) following the injury and detected the neovasculature in injured cord. Based on these preliminary results, we hypothesize that the combination of the imaging modalities (anatomical MRI, MRA, P-MRI and DCE-MRI) will increase the reliability, sensitivity and specificity of detecting morphological and vascular changes in injured SC. The MR-based measurements will provide valuable direct information on pathology, physiology and function of injured SC non-invasively, and may serve as a predictor of the final neurologic outcome from SCI. To test this hypothesis, we will perform high resolution in vivo imaging using implantable radio frequency coil in longitudinal studies of SC on injured and control rats. In conjunction with imaging, we will also carry out standard neurobehavioral tests on the animals recovering from the injury and perform quantitative end-point histological analysis on the injured cord tissue. We will statistically compare the MR-based measurements with the behavioral scores and histological findings to determine the endogenous vascular plasticity in injured SC and its role in recovery from SCI. A non-invasive determination of reorganization in vascular network of SC that is associated with the recovery of function following SCI will be a large step forward in understanding the recovery mechanisms, and in long term, objective assessment of potential new therapies with power to manipulate the SC vasculature with or without the use of exogenous processes to improve the neurofunctional outcome.