Resting State FMRI as a Biomarker of Functional Integrity of Spinal Cord

静息态 FMRI 作为脊髓功能完整性的生物标志物

• 批准号: 9981027
• 负责人: John C Gore
• 金额: $ 36.48万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981027
• 关键词: 3-Dimensional; Adopted; Animals; Back; Biological Markers; Brain; Cervical; Cervical spinal cord structure; Characteristics; Chemicals; Clinical; Clinical Management; Data; Detection; Diffusion Magnetic Resonance Imaging; Disease; Equipment; Frequencies; Functional Magnetic Resonance Imaging; Funding; Grant; Human; Image; Injury; Intervention; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Monitor; Monkeys; Motivation; Nature; Noise; Pathology; Patients; Pattern; Physical assessment; Physiologic pulse; Physiological; Property; Protocols documentation; Recovery of Function; Reporting; Reproducibility; Rest; Role; Seeds; Signal Transduction; Spinal; Spinal Cord; Spinal Cord Diseases; Spinal Injuries; Spinal cord grey matter structure; Structure; Symptoms; System; Therapeutic Intervention; Time; Tissues; Translating; Treatment outcome; Vertebral column; Work; base; blood oxygen level dependent; clinical application; clinical predictors; clinically relevant; functional disability; high risk; human subject; imaging biomarker; indexing; injury recovery; insight; neural circuit; non-invasive imaging; nonhuman primate; novel; novel therapeutics; outcome prediction; patient population; quantitative imaging; relating to nervous system; time use; tool; treatment effect; white matter

Abstract / Summary This proposal aims to extend the work performed under a recent R21 exploratory grant to detect and validate measures of functional connectivity in the human cervical spinal cord (SC) using resting state functional MRI (rsfMRI). The delineation and characterization of neural circuits within the cord may provide a valuable imaging biomarker of functional integrity of the spine applicable to a wide range of disorders. The identification of patterns of highly correlated low frequency blood oxygenation level dependent (BOLD) signals in a resting state has provided a powerful approach to delineate and describe neural circuits in the brain. We recently reported the first reliable detection of similarly correlated low frequency signal fluctuations in SC in a resting state in normal subjects, and showed how functional connectivity may be quantified in the SC both within and between segments. Moreover, in parallel studies in non-human primates we have shown that these spine circuits are selectively and specifically altered by injury and revert back over time in a manner that correlates with functional recovery. We have also shown how multi- parametric MRI can be used to derive quantitative indices of tissue composition and structure which can be related to the functional changes. We hypothesize that the intrinsic neural circuits revealed by rsfMRI in the SC are an important representation of neural synchrony within spinal segments that in turn are an essential feature of normal functions; and that alterations in the patterns of functional connectivity may be used as non-invasive imaging biomarkers of the effects of injury and of therapeutic interventions. We aim (1) to further develop robust, reliable methods to detect and quantify functional connectivity in human SC by optimizing the acquisition and analysis of images at 3T; (2) to implement a novel, multi-parametric spine MRI protocol incorporating diffusion tensor imaging and quantitative magnetization transfer imaging which provide maps of quantitative indices of tissue microstructure and composition; (3) to validate the interpretation of functional connectivity measurements and accompanying changes in white matter composition and microstructure as objective biomarkers of spinal integrity and for guiding clinical management decisions. Imaging data will be correlated with a battery of physical assessments of function in subjects with a wide range of functional impairments to demonstrate their clinical relevance. We will also evaluate their capacity for monitoring and predicting outcome of treatments in patients with cervical spondylotic myelopathy (CSM) and with traumatic spine cord injuries (SCI). The significance of the work is that it will use novel MRI methods that have proven successful in studies of the brain to objectively evaluate functional circuits within the SC, and show that connectivity measures can assess and predict clinically-relevant functions and symptoms. The ability to assess functional integrity has widespread potential for characterizing injuries to the cord, their changes over time, and for assessing novel therapies.

摘要/总结 该提案旨在扩展最近 R21 探索性资助下开展的工作，以检测和 使用静息状态验证人类颈脊髓 (SC) 功能连接的测量 功能性 MRI（rsfMRI）。脊髓内神经回路的描绘和表征可以提供 脊柱功能完整性的有价值的成像生物标志物，适用于多种疾病。 高度相关的低频血氧水平依赖性（BOLD）模式的识别 静息状态下的信号提供了一种强有力的方法来描绘和描述神经回路 脑。我们最近报告了首次可靠地检测类似相关的低频信号 正常受试者静息状态下 SC 的波动，并显示功能连接可能如何变化 在 SC 中对段内和段间进行量化。此外，在非人类的平行研究中 我们已经证明，在灵长类动物中，这些脊柱回路会因损伤和损伤而选择性地、特异性地改变。 随着时间的推移，以与功能恢复相关的方式恢复。我们还展示了如何多 参数 MRI 可用于导出组织成分和结构的定量指标，这些指标可以 与功能变化有关。我们假设 rsfMRI 揭示的内在神经回路 SC 是脊柱节段内神经同步的重要表现，而脊髓节段又是必不可少的 正常功能的特点；并且功能连接模式的改变可以用作 损伤和治疗干预效果的非侵入性成像生物标志物。我们的目标 (1) 进一步开发稳健、可靠的方法来检测和量化人类 SC 的功能连接 优化 3T 图像的采集和分析； (2) 实现新颖的多参数脊柱 MRI 协议结合了扩散张量成像和定量磁化转移成像， 提供组织微观结构和成分的定量指标图； (3) 验证 功能连接测量的解释以及白质的伴随变化 成分和微观结构作为脊柱完整性的客观生物标志物并指导临床 管理决策。成像数据将与一系列身体功能评估相关联 在具有广泛功能障碍的受试者中证明其临床相关性。我们也会 评估他们监测和预测颈椎病患者治疗结果的能力 脊髓病（CSM）和创伤性脊髓损伤（SCI）。该项工作的意义在于 它将使用在大脑研究中已被证明成功的新型 MRI 方法来客观地 评估 SC 内的功能电路，并表明连接性测量可以评估和预测 临床相关的功能和症状。评估功能完整性的能力已得到广泛应用 具有描述脊髓损伤特征、损伤随时间变化以及评估新疗法的潜力。

项目成果

Mapping Pediatric Spinal Cord Development with Age.

绘制儿童脊髓发育随年龄变化的图。

• DOI: 10.1117/12.2612210
• 发表时间: 2022
• 期刊: Proceedings of SPIE--the International Society for Optical Engineering
• 作者: Kumar,Ashwin;Vandekar,Simon;Schilling,Kurt;Bhatia,Aashim;Landman,BennettA;Smith,Seth
• 通讯作者: Smith,Seth