MRI of Angiogenesis in Spinal Cord Injury

描述(由申请人提供)：血管生成是对创伤性脊髓损伤(SCI)的反应。然而，血管生成在脊髓损伤中的作用存在争议。基于我们初步的活体纵向磁共振成像(MRI)、神经行为和终点组织学研究，我们假设血管生成有利于脊髓损伤的恢复。我们建议通过急性和长期给予血管内皮生长因子(用于促进血管生成)和抗血管内皮生长因子(中和内源性血管内皮生长因子的作用)来调节实验性脊髓损伤的血管生成活性来验证这一假说。这些化合物的效果将通过结合体内纵向多模式磁共振成像(MRI)与免疫组织化学研究和神经行为研究相结合来评估。多模式MRI研究包括高分辨率解剖、弥散张量成像(DTI)、磁化传递成像(MTI)、灌注成像和动态增强MRI(DCE MRI)。DTI和MTI将用于探测纤维束的完整性，而DCE MRI和灌注MRI将使我们能够识别和表征新生血管，确定血管密度，并绘制血-脊髓通透性图。将采用复杂的图像处理技术来生成和显示新生血管。我们将研究脊髓损伤后内源性血管内皮生长因子表达的时间变化及其与血管生成活性的关系，以期合理解释MRI结果。将进行详细的免疫组织化学研究以确定新生血管。如果证实了血管生成在脊髓损伤后康复中的作用，那么通过调控血管生成活性以增强内源性修复过程的药物治疗脊髓损伤患者应该是可能的。此外，有可能与其他治疗方法(如细胞移植)一起调节血管生成，以进一步促进脊髓损伤的恢复。因此，拟议的研究具有非常高的临床相关性。

DESCRIPTION (provided by applicant): Angiogenesis occurs in response to traumatic spinal cord injury (SCI). However, the role of angiogenesis in SCI is controversial. Based on our preliminary in vivo longitudinal magnetic resonance imaging (MRI), neurobehavioral, and end point histology studies, we hypothesize that angiogenesis is beneficial to recovery from SCI. We propose to verify this hypothesis by modulating the angiogenic activity by acute and long term administration of vascular endothelial growth factor (VEGF; for promoting angiogenesis) and anti-VEGF (neutralizing the effects of endogenous VEGF) in experimental SCI. The effect of these compounds will be assessed by combining in vivo longitudinal multi-modal magnetic resonance imaging (MRI) with immunohistochemical studies and neurobehavioral studies. The multi-modal MRI studies include high resolution anatomical, diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), perfusion imaging, and dynamic contrast enhanced MRI (DCE MRI). DTI and MTI will be used to probe the integrity of fiber tracts while DCE MRI and perfusion MRI will allow us to identify and characterize the neovasculature, determine the vascular density, and map the blood-spinal cord permeability. Sophisticated image processing techniques will be implemented for generating and displaying the neovasculature. The temporal changes in the endogenous VEGF expression and its correlation with angiogenic activity following SCI will be investigated for interpreting the MRI results on a rational basis. Detailed immunohistochemical studies will be performed for identifying neovasculature. The MRI measures will be correlated with neurobehavioral scores If the role of angiogenesis in recovery from SCI is confirmed, it should be possible to treat SCI subjects with drugs that manipulate the angiogenic activity to augment the endogenous repair processes. In addition, it is possible to modulate angiogenesis in conjunction with other treatments, such as cellular grafts to further enhance the recovery from SCI. Thus the proposed studies have a very high degree of clinical relevance.