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

摘要/摘要 该提案旨在扩大根据最近的R21探索性拨款开展的工作，以检测和 利用静息状态验证人颈脊髓功能连通性的测量 功能磁共振成像(RsfMRI)。脊髓内神经回路的描绘和特征可以提供 一种有价值的脊柱功能完整性的成像生物标记物，适用于广泛的疾病。 高度相关的低频血氧水平依赖(BOLD)模式的识别 处于休眠状态的信号提供了一种强大的方法来描绘和描述 大脑。我们最近报道了第一次可靠地检测到相似相关的低频信号 正常受试者静息状态下SC的波动，并显示了功能连接性可能是如何 在SC中量化，在部门内和部门之间都是如此。此外，在非人类的平行研究中 灵长类动物我们已经证明，这些脊椎回路是有选择地和特定地被损伤和 随着时间的推移，以与功能恢复相关的方式恢复。我们还展示了多方面的 参数磁共振成像可以用来得出组织成分和结构的定量指标，可以 与功能变化相关。我们假设rsfMRI揭示的大脑中的内在神经回路 SC是脊髓节段内神经同步性的重要代表，而脊髓节段又是必不可少的 正常功能的特征；功能连通性模式的改变可用于 损伤和治疗干预效果的非侵入性成像生物标记物。我们的目标是(1) 进一步开发稳健、可靠的方法来检测和量化人类SC的功能连通性 优化3T图像采集和分析；(2)实现一种新颖的多参数脊柱 结合扩散张量成像和定量磁化传递成像的磁共振成像方案 提供组织微观结构和成分的定量指标图；(3)验证 脑白质功能连通性测量和伴随变化的解释 成分和微结构作为脊柱完整性的客观生物标志物并用于指导临床 管理决策。成像数据将与一组功能的身体评估相关联 在具有广泛功能障碍的受试者中，以证明其临床相关性。我们还将 评价其对宫颈鳞癌患者治疗效果的监测和预测能力 脊髓型颈椎病(CSM)和创伤性脊髓损伤(SCI)。这项工作的意义在于 它将使用在大脑研究中被证明成功的新的核磁共振方法来客观地 评估SC内的功能电路，并表明连通性测量可以评估和预测 与临床相关的功能和症状。评估功能完整性的能力广泛存在 有可能确定脐带损伤的特征，它们随时间的变化，以及评估新的治疗方法。

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.