Hemodynamic basis for secondary cervical grey matter tissue loss after spinal cord injury

脊髓损伤后继发性颈灰质组织丢失的血流动力学基础

基本信息

批准号：
10599354
负责人：
ZIN Z KHAING
金额：
$ 39.16万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-15 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599354
关键词：
3-Dimensional 3D ultrasound Acute Affect Algorithms Animals Area Blood Vessels Blood coagulation Blood flow Breathing Cell Death Cerebrovascular Circulation Cervical Cervical spinal cord injury Cervical spinal cord structure Cervical spine Characteristics Clinical Trials Control Groups Custom Development Doppler Ultrasound Edema Event Family suidae Female Frequencies Glyburide Goals Grooming Hand Hand functions Hematoma Hemorrhage Histologic Human Image Imaging Techniques Individual Inflammation Injury Ischemia Legal patent Lesion Life Limb structure Longitudinal Studies Magnetic Resonance Imaging Mechanics Microbubbles Microcirculation Modeling Monitor Morphology Motor Neurologic Neurological outcome Neurons Operative Surgical Procedures Paralysed Patient-Focused Outcomes Patients Perfusion Phase Play Process Quadriplegia Quality of life Rattus Recovery Recovery of Function Research Resolution Respiration Disorders Respiratory Diaphragm Risk Rodent Rodent Model Role Secondary to Sensory Sex Differences Spinal Spinal Cord Spinal Cord Contusions Spinal cord damage Spinal cord injury Sterile coverings Surgical Decompression Swelling Techniques Testing Therapeutic Thoracic spinal cord structure Three-Dimensional Image Three-Dimensional Imaging Time Tissues Transcutaneous Electric Nerve Stimulation Trauma Ultrasonography Upper Extremity Vertebral column Visualization Work arm arm function central gray matter contrast enhanced excitotoxicity experience feeding functional improvement functional outcomes gray matter hemodynamics improved in vivo innovation insight male mechanical pressure meter nerve supply neural new technology novel preservation pressure response temporal measurement treatment effect treatment group treatment strategy ultrasound white matter

项目摘要

Abstract Currently, there is no known treatment to limit and/or protect the injured spinal cord from secondary damage in patients with spinal cord injury (SCI). More than 60% of SCIs occur at the cervical spine, resulting in respiratory dysfunction, and quadriplegia, which is the paralysis of all four limbs, severely affecting patients' quality of life. A therapeutic strategy that can reduce grey matter tissue loss could have dramatic and meaningful functional outcomes for patients with cervical SCI. The overall objective of this proposal is to examine and evaluate critical blood flow parameters that can reduce grey matter loss for improved functional recovery after cervical SCI in a rodent model. Acutely after traumatic SCI, a complete loss of blood flow occurs at the injury center and is thought to be a major contributor of the injury expansion during the secondary phase. Improving blood flow to the lesion center and adjacent tissue has long been considered desirable to mitigate the loss of neural tissue. However, until recently, there were no techniques available to monitor spinal cord blood flow in vivo in real-time. Recently, we have developed a novel intravital ultrafast ultrasound imaging technique to visualize spinal blood flow in real-time with unprecedented spatial and temporal resolution. This new technology has created a unique opportunity to evaluate local spinal hemodynamic changes in real-time. Recent work from our group has shown that ultrafast ultrasound can 1) detect distinct areas of perfusion loss, in both the grey and white matter 2) evaluate quality of peri-lesional blood flow, and 3) visualize patent spinal vessel morphology (down to ~ 50 micrometer) in a rat thoracic SCI model. Excitingly, we have now extended this work to include non- invasive 3D image acquisitions, allowing us to monitor blood flow changes within the injured spinal cord in 4D (3D imaging with time). In addition to the loss of blood flow at the lesion center, injury areas often experience progressive hemorrhaging, resulting in an expanding hematoma. We hypothesize that reducing the propagation of intraparenchymal hemorrhage and reducing elevated intraspinal pressure after SCI can improve spinal tissue perfusion and mitigate secondary grey matter loss for improved functional outcomes. Importantly, because there are known sex differences in cerebral blood flow and response to spinal cord injury, we will examine the hemodynamic changes after cervical SCI in both males and females. By applying this innovative ultrasound imaging, we aim to (1) discover critical perfusion thresholds for grey matter tissue at risk, (2) monitor spatial and temporal development of the intraparenchymal hematoma, and (3) evaluate treatment effects of reducing raised intraspinal pressure in real-time. Overall, these studies will provide direct insights into the critical hemodynamic changes within the microcirculation of the spinal cord, as well as effective ways of limiting secondary grey matter damage for improved functional recovery after SCI.

抽象的目前，没有已知的治疗方法可以限制和/或保护受伤的脊髓免受继发性损伤。脊髓损伤（SCI）患者的损伤。超过 60% 的 SCI 发生在颈椎，导致呼吸功能障碍和四肢瘫痪，严重影响患者的生活生活质量。一种可以减少灰质组织损失的治疗策略可能会产生巨大的效果对颈椎 SCI 患者有意义的功能结果。该提案的总体目标是检查和评估关键血流参数，这些参数可以减少灰质损失，从而改善功能啮齿动物模型中颈椎 SCI 后的恢复。创伤性 SCI 后急性损伤中心发生血流完全丧失，这被认为是是第二阶段损伤扩大的主要因素。改善病变部位的血流长期以来，中心和邻近组织一直被认为是减轻神经组织损失的理想选择。然而，直到最近，还没有可用于实时监测体内脊髓血流的技术。最近，我们开发了一种新颖的活体超快超声成像技术来可视化脊柱具有前所未有的空间和时间分辨率的实时血流。这项新技术创造了这是实时评估局部脊柱血流动力学变化的独特机会。我们小组最近的工作已经表明，超快超声可以 1) 检测灰色和白色区域的不同灌注损失区域重要的是 2) 评估病灶周围血流的质量，以及 3) 可视化开放的脊髓血管形态（低至 ~ 50 微米）在大鼠胸部 SCI 模型中。令人兴奋的是，我们现在已将这项工作扩展到包括非侵入式 3D 图像采集，使我们能够监测受伤脊髓内的血流变化 4D（随时间的 3D 成像）。除了病变中心的血流丧失外，损伤区域也经常经历进行性出血，导致血肿扩大。我们假设减少 SCI 后脑实质内出血的扩散和降低椎内压升高可以改善脊柱组织灌注并减轻继发性灰质损失，从而改善功能结果。重要的是，因为已知脑血流量和对脊柱的反应存在性别差异脊髓损伤后，我们将检查男性和女性颈椎 SCI 后的血流动力学变化。经过应用这种创新的超声成像，我们的目标是 (1) 发现灰质的关键灌注阈值处于危险中的组织，(2) 监测实质内血肿的空间和时间发展，以及 (3) 实时评估降低椎管内压力升高的治疗效果。总体而言，这些研究将提供对脊髓微循环内关键血流动力学变化的直接见解，如以及限制继发性灰质损伤以改善 SCI 后功能恢复的有效方法。