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.

项目概要/摘要 功能超声 (fUS) 成像是标准功能神经成像的一种相对较新的替代方案 方法（例如，fMRI、PET）利用超快平面波脉冲方案来实现改进的信号到 噪声比和时空分辨率（1 毫秒，100 µm）。然而，目前的 fUS 方法隔离血流 仅基于相对速度的组织运动信号。这导致排除慢速 微循环流量，鉴于最近毛细血管在直接调节中的影响，这是一个关键限制 脑和脊髓的血流量。该项目的主要目标是开发一种对微循环敏感的 fUS 模式利用循环微泡造影剂的非线性激发。颈脊髓 损伤（SCI）将被用作开发这种新方法和随后评估的模型 它的效用。具体来说，间歇性缺氧（IH）是一种有前途的诱导神经可塑性和 恢复慢性 SCI 中的健康呼吸功能，将用于诱导局部激活和长期治疗 促进膈运动神经元池。一、对比增强功能超声（CE-fUS）成像 在完整的脊髓中进行的将用于优化传输参数（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）。 将利用时空过滤技术来分离组织灌注和更大的微血管血流信号 进行独立分析，这是迄今为止现有的 fUS 成像技术不可能实现的。 CE-fUS 成像随后将 用于表征以下病灶周围区域神经血管耦合的初始退化 受控挫伤 SCI，以及反复 IH 暴露引起的后续基本微血管变化 在损伤的慢性阶段。成功完成这些研究将阐明基本原理 SCI 后介导 IH 诱导的神经可塑性的微血管变化。此外，CE-fUS 成像将 能够进一步研究不同水平脉管系统的差异血流动力学反应模式，以及 将作为评估神经血管病理学和发育疗法的基本工具 在今后的工作中。