Long Term Clinical Correlates of TBI: Imaging, Biomarkers, Clinical Phenotyping

这项研究于2010年3月17日获得CNS IRB Blue批准。研究团队人员齐全，我们正在积极招募患者参加这一方案。 2011年7月，我们获得了IRB的批准，进行了一项子研究，将研究纳入标准扩大到受伤后5年。子研究将主要集中于收集TBI通用数据元素(CDE)、血统和想象。 2012年6月，IRB批准将我们的注册年龄范围从18-70岁扩大到18岁及以上。在协议的成像部分，同样的修改将PET-CT替换为PET-MRI。增加了关于提供治疗的一节，以满足那些有功能需要但获得社区资源有限的受试者的需要。 2014年底，IRB批准收集超高场(7特斯拉)成像参数，核磁共振中心每月分配时间。7T磁铁已经被用来扫描冲击性和非冲击性脑外伤患者，以确定是否可以在超高场下检测到损伤类型之间的差异。 2015年9月，IRB批准扩大我们的研究人群，增加一个健康的志愿者对照组。此外，我们注意到，当地的脑损伤患者人口并不是正态分布的，其教育水平略高于平均水平。尽管比较结果的标准数据在人口统计学上进行了调整，但与来自相同人群的对照组的直接比较将为我们的发现提供支持。在该议定书的早期版本中，讨论了设立控制组的必要性。然而，直到当地脑外伤人群的人口学特征已知，并且健康对照可以与患者人群相匹配时，才决定暂缓设立对照组。 将健康志愿者的对照组纳入数据集，可以直接与当地正常样本进行比较。因此，在同一扫描仪上同时收集对照组和患者群体的成像数据将为这项研究提供实质性的影响。在当地健康志愿者样本群体中收集相同的临床相关性，就像在脑外伤人群中所做的那样，将在评估新的诊断成像和生物标记物技术时满足这一关键需求。在这项研究中，这一对照人群可能需要与各种患者人口统计学以及任何可能影响我们的成像或血清结果的共病疾病相匹配。 评估语言、话语和社会认知的其他SLP措施已被添加到议定书中。话语措施将包括录音和/或录像。语篇分析是对程序性、叙事性、对话性和其他语篇任务中的语言和非言语行为的评估。将健康志愿者与年龄相近、性别匹配的脑外伤患者配对，比较脑外伤患者与非脑损伤患者的话语测量。 前几年的修正案增加了健康志愿者的登记人数，并增加了日程安排和进行方案评估的灵活性。NIH的工作人员/雇员已被添加为潜在的研究参与者。根据FDA的指导，添加了语言以反映有关造影剂的预防措施。2022年，精选暴露(SEG)参与者的登记人数增加到96人。这些参与者被美国一家政府机构确认为可能接触到非天然能源，他们有脑损伤症状，并进行了纵向研究。听觉和前庭测试也被添加到协议中。此外，还将招募96名未受影响的匹配健康志愿者。正电子发射断层扫描被从研究中删除，它将研究风险分类更改为不超过最低风险。 在过去的一年(FY22)，我们修改了方案，从我们的扫描中删除了对比度，并进一步将SEG和他们的对照组的数量从96人增加到115人，因为我们被转诊的全球病例增加了。此外，我们开始了初步的探索性分析，并正在准备数据以供传播。 展望未来，我们继续在我们的队列中收集预期的数据，并计划未来的出版物，以呈现纵向数据供同行审查。

This study received CNS IRB Blue approval on March 17, 2010. The study team is fully staffed and we are actively recruiting patients for this protocol. In July 2011 we received IRB approval for a sub-study that broadens the study inclusion criteria up to 5 years since injury. The sub-study will focus on collecting primarily the TBI Common Data Elements (CDEs), bloods, and imagining. In June 2012 the IRB approved expanding our enrollment age range from 18-70, to 18 and older. This same amendment exchanged PET-CT for PET-MRI in the imaging section of the protocol. A section regarding offered treatment was added to address the needs of those subjects who have functional needs with limited access to community resources. At the end of 2014 approval to collect ultra-high field (7 Tesla) imaging parameters was granted by the IRB and the NMR Center allotted time monthly. The 7T magnet has been used to scan both blast and non-blast TBI patients in order to determine if differences between the types of injury can be detected at ultra-high field. In September 2015, the IRB approved expanding our study population with the addition of a healthy volunteer control group. Additionally, we have noted that the local TBI patient population is not normally distributed and has a somewhat higher level of education than average. Although normative data to which results are compared is demographically adjusted, direct comparisons to a control group from the same population will add support to our findings. In earlier versions of the protocol the need for a control group was discussed. However, the decision to hold off on a control group was made until the demographics of the local TBI population was known and healthy controls could be matched to the patient population. Including a control group of healthy volunteers to the data set provides direct comparisons to be made with a normal local sample. Therefore, collecting imaging data on a control group on the identical scanner concurrently with the patient population would provide substantial influence to this research. Collecting the same clinical correlates on a local healthy volunteer sample population, as done in the TBI population, will address this critical need when assessing novel diagnostic imaging and biomarkers techniques. In the case of this study, this control population may need to be matched for a variety of patient demographics as well as any co-morbid illnesses that might affect our imaging or serum results. Additional SLP measures assessing language, discourse, and social cognition have been added to the protocol. Discourse measures will include audio and/or video recording. The discourse analysis is an assessment of language and nonverbal behaviors during procedural, narrative, conversational, and other discourse tasks. Healthy Volunteers are paired with TBI patients of similar age and matching gender, to compare discourse measures between individuals with and without a TBI. Amendments in previous years increased enrollment of healthy volunteers and, added increased flexibility for scheduling and conducting protocol assessments. NIH staff/employees have been added as potential study participants. As per FDA guidance, language was added to reflect precaution regarding contrast agents. Enrollment of Select Exposure (SEG) participants was increased to 96 in 2022. These participants, who have been identified by a US governmental agency as potentially being exposed to a non-natural energy source, with TBI symptomology are studied longitudinally. Auditory and vestibular testing was also added to the protocol. In addition, 96 unaffected matched Healthy Volunteers will also be enrolled. Postitron Emission Tomography was removed from the study, which changed study risk classification to no more than minimal risk. In the past year (FY22), we amended the protocol remove contrast from our scans and further increased the number of SEG and their control group from 96 to 115, due to the increase in worldwide cases we were being referred. Additionally, we began initial exploratory analysis and are preparing data for dissemination. Moving forward, we continue to collect prospective data in our cohorts and plan future publications to present the longitudinal data for peer-review.