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: 9423271
• 负责人: John C Gore
• 金额: $ 34.52万
• 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 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9423271
• 关键词: 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; Image Analysis; 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; 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; 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 /摘要 该建议旨在扩大根据R21探索赠款进行的工作，以检测和 使用静止状态验证人颈脊髓（SC）中功能连通性的度量 功能性MRI（RSFMRI）。电线内神经回路的描述和表征可以提供 适用于多种疾病的脊柱功能完整性的有价值的成像生物标志物。 高度相关的低频血液氧合水平依赖（BOLD）的模式的鉴定 在休息状态下的信号提供了一种有力的方法来描述和描述神经回路 脑。我们最近报道了对类似相关的低频信号的首次可靠检测 在正常受试者中，在静止状态下SC的波动，并显示了功能连通性的可能性 在段内和段之间的SC中量化。此外，在非人类的平行研究中 灵长类动物我们已经表明，这些脊柱电路被选择性地，特异性地通过伤害和 随着时间的流逝，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可用于得出组织组成和结构的定量指标 与功能变化有关。我们假设RSFMRI在 SC是脊柱段内神经同步的重要表示，而这反过来是必不可少的 正常功能的特征；功能连接模式的改变可以用作 损伤和治疗干预措施的影响的非侵入性成像生物标志物。我们的目标（1） 通过 优化3T图像的获取和分析； （2）实施一个新颖的多参数脊柱 MRI协议融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组成的定量指标图； （3）验证 功能连接测量和随附的白质变化的解释 组成和微观结构作为脊柱完整性的客观生物标志物和指导临床 管理决策。成像数据将与功能的一系列物理评估相关 在具有广泛功能障碍的受试者中，以证明其临床相关性。我们也会 评估其监测和预测宫颈患者治疗结果的能力 脊柱脊髓病（CSM）和创伤性脊柱绳索损伤（SCI）。工作的意义是 它将使用已证明在大脑研究中成功的新型MRI方法来客观地 评估SC内的功能电路，并表明连接度量可以评估和预测 临床上的功能和症状。评估功能完整性的能力已广泛 表征绳索伤害的潜力，随着时间的流逝而变化以及评估新疗法的潜力。