Development of Contrast Enhanced Functional Ultrasound Imaging to Monitor Induced Neuroplasticity in Chronic Spinal Cord Injury

开发对比增强功能超声成像来监测慢性脊髓损伤的诱导神经可塑性

• 批准号: 10581486
• 负责人: Jennifer Harmon
• 金额: $ 7.22万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10581486
• 关键词: Air; Animals; Assessment tool; Beds; Blood Vessels; Blood capillaries; Blood flow; Breathing; Central Nervous System; Cerebrum; Cervical spinal cord injury; Cervical spinal cord structure; Chronic; Chronic Phase; Compensation; Contrast Media; Development; Developmental Therapeutics Program; Disease; Doppler Ultrasound; Electroencephalography; Exclusion; Fellowship; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Human; Hyperactivity; Hypoxia; Image; Imaging Device; Imaging Techniques; Impairment; Individual; Injury; Investigation; Linear Models; Longevity; Lung; Mediating; Methods; Microbubbles; Microcirculation; Modality; Modeling; Monitor; Motion; Motor; Motor Neurons; Nervous System; Neural Pathways; Neuronal Plasticity; Neurons; Noise; Oxygen; Pathologic; Pathology; Patients; Pattern; Perfusion; Periodicity; Physiologic pulse; Physiological; Plethysmography; Positron-Emission Tomography; Pre-Clinical Model; Regulation; Resolution; Respiration; Respiratory Diaphragm; Rodent; Scheme; Signal Transduction; Site; Spinal Cord; Spinal Cord Contusions; Spinal cord injury; Structure of phrenic nerve; Techniques; Testing; Time; Tissues; Trees; Ultrasonography; Vascular System; Visualization; Work; contrast enhanced; experimental study; hemodynamics; imaging approach; imaging modality; improved; infection rate; injured; innovation; meter; millisecond; model development; neuroimaging; neurovascular; neurovascular coupling; novel; novel therapeutics; respiratory; response; restoration; spatiotemporal; tool; transmission process; ultrasound

Project Summary/Abstract Functional ultrasound (fUS) imaging is a relatively new alternative to standard functional neuroimaging approaches (e.g., fMRI, PET) that utilizes ultrafast plane wave pulsing schemes to achieve improved signal-to- noise ratio and spatiotemporal resolution (1 msec, 100 µm). However, current fUS approaches isolate blood flow signal from tissue motion solely on the basis of relative velocity. This results in the exclusion of slow microcirculatory flows, a critical limitation given the recent implication of capillaries in the direct regulation of cerebral and spinal cord blood flow. The primary goal of this project is to develop a microcirculation-sensitive fUS modality by utilizing nonlinear excitation of circulating microbubble contrast agents. Cervical spinal cord injury (SCI) will be utilized as a model for the development of this new method and subsequent assessment of its utility. Specifically, intermittent hypoxia (IH), a promising method for the induction of neuroplasticity and restoration of healthy breathing function in chronic SCI, will be used to induce localized activation and long term facilitation in the phrenic motor neuron pool. First, contrast-enhanced functional ultrasound (CE-fUS) imaging conducted in the intact spinal cord will be utilized to optimize transmit parameters (i.e., pulse repetition frequency, nonlinear pulsing schemes) and post-processing methods (i.e., motion correction, generalized linear modeling). Spatiotemporal filtering techniques will be utilized to isolate tissue perfusion and larger microvascular flow signals for independent analysis, heretofore impossible with existing fUS imaging techniques. CE-fUS imaging will then be applied to characterize the initial degeneration of neurovascular coupling in the perilesional region following controlled contusion SCI, and subsequent fundamental microvascular changes induced by repeated IH exposure during the chronic phase of injury. Successful completion of these studies will elucidate the fundamental microvascular changes that mediate IH-induced neuroplasticity following SCI. Moreover, CE-fUS imaging will enable further studies of differential hemodynamic response patterns at different levels of the vasculature, and will serve as a fundamental tool for the assessment of neurovascular pathologies and developmental therapies in future work.

项目摘要/摘要 功能超声(Fus)成像是一种相对较新的替代标准功能神经成像的方法。 利用超快平面波脉冲方案实现改进的信号到信号比的方法(例如，fMRI、PET) 噪声比和时空分辨率(1毫秒，100微米)。然而，目前的FUS方法隔离了血流。 仅基于相对速度的来自组织运动的信号。这导致排除了慢速 微循环流动，一个关键的限制，考虑到最近毛细血管在直接调节 大脑和脊髓的血流量。这个项目的主要目标是开发一种对微循环敏感的 利用循环微泡造影剂的非线性激发进行FUS检查。颈髓 损伤(SCI)将被用作这一新方法的开发和后续评估的模型。 它的效用。特别是，间歇性低氧(IH)，一种有希望的神经可塑性诱导方法和 慢性脊髓损伤患者健康呼吸功能的恢复将被用于诱导局部和长期的激活 在膈运动神经元池中的促进作用。第一，对比增强功能超声(CE-FUS)成像 在完整的脊髓中进行的传导将被用于优化传输参数(即，脉冲重复频率， 非线性脉冲方案)和后处理方法(即运动校正、广义线性建模)。 时空滤波技术将被用来分离组织灌注和更大的微血管血流信号 对于独立分析，到目前为止，使用现有的FUS成像技术是不可能的。到那时，CE-FUS成像将 用来描述损伤周围区神经血管偶联的初始变性 反复暴露IH引起的受控挫伤脊髓损伤和随后的基础微血管改变 在受伤的慢性期。这些研究的成功完成将阐明 脊髓损伤后微血管改变介导IH诱导的神经可塑性。此外，CE-FUS成像将 能够进一步研究不同水平的血管系统的不同血流动力学反应模式，以及 将作为评估神经血管病理和发育疗法的基本工具 在今后的工作中。