Cortical functional connectivity as an early biomarker of recovery in spinal cord injury

项目摘要 脊髓损伤（SCI）治疗干预计划的早期检测反应是至关重要的，因为它将 使无应答患者能够提前终止干预，避免不必要的经济负担，以及 允许及时修改程序。在这个项目中，我们提出静息态功能MRI（rsfMRI）可以 用于检测干预期间发生的早期脑功能网络变化， 这些变化将预测慢性SCI患者的恢复。这项研究的长期目标是建立 rsfMRI作为一种新的成像生物标志物，可预测治疗后的恢复进展。 国际脊髓损伤神经病学分类标准（ISNCSCI）评分系统是 最广泛使用的SCI临床分类系统，描述神经损伤水平和程度， 功能保存。它还用于监测干预措施的进展和反应，如功能性 电刺激（FES）疗法。然而，使用ISNSCI监测响应具有挑战性，因为其 描述功能丧失程度的能力有限。因此，在SCI领域需要一个 生物标志物对功能变化更敏感。 在本项目的目标1中，我们将描述慢性脑梗死患者皮层重组的基线时间曲线， SCI患者在4周的被动FES循环计划中发生，其中运动仅由 自行车的马达（无电刺激）。在第0、2和4周获得的患者的RsfMRI数据将被 分析以使用独立分量执行感觉运动皮层的功能分组 分析（伊卡）和谱聚类分析（SCA）方法。由此产生的感觉运动的BNC测量 然后计算皮质包裹。还将在第0、2和4周测量患者的ISNCSCI评分。 4，为了检验我们将观察到感觉运动皮层BNC和ISNCSCI的最小变化或无变化的假设， 被动FES循环4周后患者的评分。在本项目的目标2中，我们将描述 慢性SCI患者在四周（活动）FES期间发生的皮质重组的时间曲线 骑自行车具体来说，我们预测，我们将观察到早期的功能网络的变化，在感觉运动 在为期四周的FES循环计划的第2周，SCI患者的皮质（使用BNC测量）， 预测第4周ISNSCI评分（神经学结局）的变化。 如果成功，该研究将：1）提供一种新的有效的临床工具来研究可塑性皮质变化， 2）提供一种新的非侵入性成像生物标志物，可预测SCI后的进展， 恢复对治疗的反应，3）扩展我们对功能重组的知识， 在治疗期间和之后。

PROJECT SUMMARY Early detection of response to spinal cord injury (SCI) therapeutic intervention programs is vital, as it will enable early termination of intervention in non-responding patients, prevent unnecessary financial burden, and allow for timely program modifications. In this project, we propose that resting state functional MRI (rsfMRI) can be used to detect early brain functional network changes that occur during an intervention, and that the changes will be predictive of recovery in chronic SCI patients. The long-term goal of this study is to establish rsfMRI as a new imaging biomarker that is predictive of progress towards recovery in response to therapy. International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) scoring system is the most widely used clinical classification system of SCI that describes neurological injury level and degree of functional preservation. It is also used to monitor the progress and response to interventions such as functional electrical stimulation (FES) therapy. However, monitoring responses using ISNSCI is challenging because its ability to describe the degree of functional loss is limited. Therefore, there is a need in the field of SCI for a biomarker that is more sensitive to changes in function. In Aim 1 of this project, we will characterize the baseline time profile of the cortical reorganization in chronic SCI patients that occurs during a 4-weeks program of passive FES cycling, where movement is driven only by the cycle’s motor (no electric stimulation). RsfMRI data of the patients acquired at weeks 0, 2, and 4 will be analyzed to perform functional parcellation of the sensorimotor cortex, using the independent component analysis (ICA) and spectral clustering analysis (SCA) methods. BNC measures of the resulting sensorimotor cortex parcels will then be calculated. ISNCSCI scores of the patients will also be measured at weeks 0, 2, and 4, to test the hypothesis that we will observe minimal to no changes in sensorimotor cortex BNC and ISNCSCI scores of the patients after 4 weeks of passive FES cycling. In Aim 2 of this project, we will characterize the time profile of the cortical reorganization in chronic SCI patients that occurs during the four-week (active) FES cycling. Specifically, we predict that we will observe early functional network changes in the sensorimotor cortex of SCI patients (measured using BNC) at week 2 of the four-week FES cycling program, which will be predictive of changes in ISNSCI scores (neurological outcomes) at week 4. If successful, the study will: 1) provide a new and effective clinical tool to study plastic cortical changes that occur after SCI, 2) provide a new non-invasive imaging biomarker that is predictive of progress towards recovery in response to therapy, and 3) extend our knowledge about the functional reorganization that takes place during and after therapeutic intervention.