Noninvasive Spinal Cord Perfusion Techniques with MRI

该提案旨在建立脊髓灌注磁共振成像（MRI）作为一种 翻译工具和急性脊髓损伤（SCI）后继发性损伤的预测生物标志物。在SCI中， 最大限度地减少初始损伤（即继发性损伤）之后发生的损伤被认为是主要损伤 治疗靶点当前急性SCI护理的临床建议提倡脊髓恢复 灌注，以减少继发性损伤，并提供最大的机会，改善神经功能的结果。 然而，脊髓灌注状态在SCI患者中并没有常规监测，并且缺乏无创性的 工具在很大程度上阻碍了SCI的个性化护理。值得注意的是，虽然灌注磁共振 在100多项研究中报告了大脑的MRI，几乎完全没有灌注 MRI研究应用于脊髓，尽管其改善患者结局的潜力很大。我们之前 显示啮齿动物脊髓的扩散MRI，与对轴突损伤唯一敏感的对比， 高准确度地预测损伤严重程度和神经系统结局。随着我们最近在高科技领域的进展， 分辨率扩散MRI，脊髓内损伤的位置和范围与个人的细节可视化 科目因此，我们的中心假设是，虽然弥散MRI检测到SCI后急性不可逆损伤， 灌注MRI缺陷反映了在没有干预的情况下存在继发性损伤风险的组织。我们 初步研究证实了获得胸椎高分辨率灌注MRI的可行性 线.我们建议在大鼠挫伤SCI模型中使用体内MRI来增强和调整灌注 对脊髓进行MRI，以准确、高效和高分辨率询问灌注状态（目标2） 表征大鼠急性脊髓创伤性损伤后的灌注和扩散缺陷，以区分 之间的可逆性和不可逆性损伤，和（目的3）证明灌注MRI的效用， 非侵入性监测临床推荐的干预措施。总的来说，这些研究将提供一个强有力的 促进先进MRI在SCI个性化护理中转化应用的技术和科学基础 患者这些转化研究旨在实现无创成像的全部临床效用， 结果，如毁灭性的伤害及其对生活质量的不利影响。

This proposal aims to establish perfusion magnetic resonance imaging (MRI) of the spinal cord as a translational tool and predictive biomarker of secondary damage after acute spinal cord injury (SCI). In SCI, minimizing damage that occurs beyond the initial insult (i.e. secondary injury) is considered a primary therapeutic target. Current clinical recommendations for acute SCI care advocate restoration of spinal cord perfusion to reduce secondary injury and provide the greatest chance for improved neurological outcome. However, spinal cord perfusion status is not routinely monitored in SCI patients, and the lack of noninvasive tools considerably impedes personalized care in SCI. Remarkably, while perfusion magnetic resonance imaging (MRI) of the brain has been reported in 100s of studies, there is almost a complete void of perfusion MRI studies applied to the spinal cord despite its high potential to improve patient outcomes. We previously showed that diffusion MRI of the rodent spinal cord, with contrast uniquely sensitized to axonal injury, could predict injury severity and neurological outcomes with high accuracy. With our recent advances in high resolution diffusion MRI, the location and extent of injury within the cord was visualized with detail in individual subjects. Thus, our central hypothesis is that while diffusion MRI detects irreversible injury acutely after SCI, perfusion MRI deficits reflect tissue at risk of secondary injury in the absence of an intervention. Our preliminary studies demonstrate the feasibility of obtaining high resolution perfusion MRI of the thoracic spinal cord. We propose to use in vivo MRI in a rat model of contusion SCI to (Aim 1) enhance and tailor perfusion MRI to the spinal cord for accurate, efficient, and high-resolution interrogation of perfusion status, (Aim 2) characterize perfusion and diffusion deficits after acute spinal cord traumatic injury in the rat to distinguish between reversible and non-reversible injury, and (Aim 3) demonstrate the utility of perfusion MRI to noninvasively monitor clinically-recommended interventions. Overall, these studies will provide a strong technical and scientific foundation to promote translational use of advanced MRI for personalized care of SCI patients. These translational studies aim to realize the full clinical utility of noninvasive imaging to maximize outcomes from such as devastating injury and its detrimental impact on quality-of-life.