Vascular plasticity in Injured Spinal Cord - Investigations using MRI

描述(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)为研究损伤脊髓(SC)提供了具有精细软组织对比的活体三维图像。在对大鼠脊髓损伤模型的实验研究中，我们定期使用MRI对同一动物进行纵向跟踪，以便每种动物都可以作为自己的对照。然而，常规MRI提供的关于损伤后发生的短暂血管变化的信息有限。需要具有感知血管变化能力的新的成像方法。作为潜在的成像手段，我们最近探索了磁共振血管成像(MRA)和灌注磁共振成像(P-MRI)技术来探测大鼠SC的血管系统。我们的初步数据显示，MRA能够产生高分辨率的大血管投射图，为大鼠SC提供血液，而P-MRI对脊髓组织内的微血管系统很敏感。使用造影剂加多巴喷丁(Gd)，我们还生成了更详细地描绘脊髓血管的血管造影。在纵向动态增强磁共振成像(DCE-MRI)研究中，我们已经量化了损伤后血脊髓屏障(BSCB)通透性的时间变化，并检测了损伤脊髓的新生血管。基于这些初步结果，我们推测联合应用影像技术(解剖MRI、MRA、P-MRI和DCE-MRI)将提高检测损伤SC形态和血管改变的可靠性、敏感性和特异性。基于MR的测量将无创性地提供关于损伤SC的病理、生理和功能的有价值的直接信息，并可能作为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对损伤和对照大鼠的SC进行纵向研究，进行高分辨率的活体成像。在成像的同时，我们还将对从损伤中恢复的动物进行标准的神经行为测试，并对损伤的脊髓组织进行定量的终点组织学分析。我们将把基于MR的测量结果与行为评分和组织学结果进行统计学比较，以确定受损SC的内源性血管可塑性及其在脊髓损伤后恢复中的作用。与脊髓损伤后功能恢复相关的SC血管网络重组的无创性测定将是理解SCI恢复机制的一大进步，从长远来看，客观评估潜在的新疗法的能力，无论是否使用外源性过程来改善神经功能结果。

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.