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

• 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
• 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

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，尚无已知的治疗方法来限制和/或保护受伤的脊髓免受次要 脊髓损伤患者（SCI）的损害。超过60％的SCI发生在颈椎，导致 呼吸功能障碍和四肢瘫痪，这是所有四肢的麻痹，严重影响患者 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影响，并且 宫颈SCI患者的有意义的功能结果。该提议的总体目的是 检查和评估关键的血流参数，以减少灰质损失以提高功能 啮齿动物模型中的宫颈SCI后恢复。 创伤后急性，在伤害中心发生完全流动的完全损失，被认为是 在第二阶段成为损伤扩张的主要因素。改善流向病变的血液流动 长期以来，中心和邻近组织被认为可以减轻神经组织的丧失。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，我们开发了一种新型的插入性超级超声成像技术来可视化脊柱 实时血液流动，并以空前的空间和时间分辨率。这项新技术创造了 一个独特的机会，可以评估实时局部血液动力学变化。我们小组的最新工作 已经表明超声超声可以1）检测灰色和白色的不同区域 物质2）评估流体流动流量的质量，3）可视化专利的脊柱形态（向下至 〜50千分尺）在大鼠胸科SCI模型中。令人兴奋的是，我们现在已经扩展了这项工作，以包括非 - 侵入性的3D图像采集，使我们能够监测受伤的脊髓中的血流变化 在4D（随时间的3D成像）中。除了病变中心的血液流量损失外，伤害区域经常 经历渐进性出血，导致血肿的膨胀。我们假设减少了 科学后掌内出血的传播和降低的脊柱内压力升高 可以改善脊柱组织灌注并减轻次级灰质损失，以提高功能 结果。重要的是，因为脑血流有已知的性别差异和对脊柱的反应 脐带损伤，我们将检查男性和女性宫颈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 有风险的组织，（2）监测核内血肿的空间和时间发育，（3） 评估实时降低升高内压力的治疗效果。总体而言，这些研究将 直接见解脊髓微循环中的临界血流动力学变化，如 以及限制继发性灰质损害的有效方法，以改善SCI后功能恢复。