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仍存在争议。根据我们初步的体内纵向磁共振成像（MRI）、神经行为学和终点组织学研究，我们假设血管生成有助于脊髓损伤的恢复。我们建议在实验性SCI中通过急性和长期给予血管内皮生长因子（VEGF；促进血管生成）和抗VEGF（中和内源性VEGF的作用）来调节血管生成活性来验证这一假设。这些化合物的效果将通过体内纵向多模态磁共振成像（MRI）与免疫组织化学研究和神经行为研究相结合来评估。多模态MRI研究包括高分辨率解剖学、扩散张量成像（DTI）、磁化转移成像（MTI）、灌注成像和动态对比增强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血管系统，确定血管密度，并绘制血脊髓通透性图。复杂的图像处理技术将用于生成和显示新的血管系统。我们将研究脊髓损伤后内源性VEGF表达的时间变化及其与血管生成活性的相关性，以合理地解释MRI结果。将进行详细的免疫组织化学研究以确定新血管。如果血管生成在脊髓损伤恢复中的作用得到证实，那么就有可能通过药物控制血管生成活性来增强内源性修复过程来治疗脊髓损伤受试者。此外，与其他治疗方法（如细胞移植）联合调节血管生成也有可能进一步增强脊髓损伤后的恢复。因此，提出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.