MRI of Angiogenesis in Spinal Cord Injury

脊髓损伤血管生成的 MRI

• 批准号: 7105461
• 负责人: PONNADA A NARAYANA
• 金额: $ 57.01万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-03 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105461
• 关键词: angiogenesis; diffusion magnetic resonance imaging; hormone therapy; image processing; immunocytochemistry; laboratory rat; longitudinal animal study; magnetic resonance imaging; neural plasticity; neurophysiology; nonhuman therapy evaluation; regeneration; spinal cord imaging /visualization; spinal cord injury; statistics /biometry; vascular endothelial growth factors; western blottings

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.

描述（由申请人提供）：血管生成是响应创伤性脊髓损伤（SCI）而发生的。然而，血管生成在 SCI 中的作用存在争议。根据我们初步的体内纵向磁共振成像 (MRI)、神经行为和终点组织学研究，我们假设血管生成有利于 SCI 的恢复。我们建议通过在实验性 SCI 中急性和长期施用血管内皮生长因子（VEGF；用于促进血管生成）和抗 VEGF（中和内源性 VEGF 的影响）来调节血管生成活性来验证这一假设。这些化合物的作用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、弥散张量成像 (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液脊髓通透性图。将采用复杂的图像处理技术来生成和显示新血管系统。将研究 SCI 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，以便合理解释 MRI 结果。将进行详细的免疫组织化学研究以鉴定新血管系统。 MRI 测量结果将与神经行为评分相关。如果血管生成在 SCI 恢复中的作用得到证实，那么应该可以使用操纵血管生成活性以增强内源性修复过程的药物来治疗 SCI 受试者。此外，还可以结合其他治疗（例如细胞移植）来调节血管生成，以进一步促进 SCI 的恢复。因此，拟议的研究具有非常高的临床相关性。