Noninvasive Spinal Cord Perfusion Techniques with MRI

这项建议旨在建立脊髓的灌注磁共振成像(MRI)作为一种 急性脊髓损伤(SCI)后继发性损伤的翻译工具和预测生物标志物。在SCI中， 将初次伤害(即二次伤害)以外的伤害降至最低被认为是主要伤害 治疗靶点。当前急性脊髓损伤治疗的临床建议提倡脊髓恢复 灌注可减少继发性损伤，并提供最大机会改善神经预后。 然而，脊髓损伤患者的脊髓血流灌注状态没有得到常规监测，而且缺乏无创的 工具在很大程度上阻碍了SCI的个性化护理。值得注意的是，当灌注磁共振 脑部的成像(MRI)已经报道了100多年的研究，几乎完全没有脑血流灌注 尽管脊髓具有改善患者预后的高潜力，但MRI研究仍适用于脊髓。我们之前 结果显示，啮齿动物脊髓的弥散磁共振成像，加上对轴突损伤唯一敏感的对比剂，可以 高精度地预测损伤严重程度和神经预后。随着我们在高科技领域的最新进展 分辨率弥散磁共振成像显示脊髓内损伤的位置和程度 研究对象。因此，我们的中心假设是，虽然扩散磁共振成像可以迅速检测到脊髓损伤后不可逆转的损伤， 磁共振灌注成像缺陷反映了在缺乏干预的情况下存在二次损伤风险的组织。我们的 初步研究证实获得高分辨率胸椎核磁共振灌注成像的可行性 电源线。我们建议在大鼠脊髓挫伤模型中使用活体磁共振成像来(目标1)增强和定制灌注 用于准确、高效和高分辨率询问血流状态的脊髓MRI(目标2) 表征大鼠急性脊髓损伤后的血流和弥散功能缺陷以区分 可逆性和不可逆性损伤之间的区别，以及(目标3)展示了磁共振灌注成像在 无创监测临床推荐的干预措施。总体而言，这些研究将提供强有力的 促进先进磁共振成像在脊髓损伤个性化护理中的应用的技术和科学基础 病人。这些转化性研究旨在实现非侵入性成像的全部临床效用，以最大限度地 造成毁灭性伤害的后果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.