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

TBI 的长期临床相关性：影像学、生物标志物、临床表型

• 批准号: 10928546
• 负责人: Leighton Chan
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10928546
• 关键词: Address; Affect; Age; Agreement; Amendment; Auditory; Behavior; Biological Markers; Blood; Case Study; Cells; Clinical; Cognitive; Common Data Element; Communities; Contrast Media; Control Groups; Data; Data Set; Databases; Diagnostic Imaging; Discourse analysis; Educational Status; Employee; Energy-Generating Resources; Enrollment; Exposure to; Future; Gender; Generations; Grant; Hematology; Image; Individual; Injury; Institutional Review Boards; Language; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medical History; Natural History; Outcome; Outcome Measure; PET/CT scan; Participant; Pathology; Patient Recruitments; Patients; Peer Review; Persons; Phenotype; Population; Population Control; Positron-Emission Tomography; Prospective, cohort study; Protocols documentation; Publications; Records; Recruitment Activity; Research; Research Personnel; Resources; Saliva; Sampling; Scanning; Schedule; Series; Serum; Severities; TBI Patients; Taxonomy; Techniques; Testing; Time; Traumatic Brain Injury; Travel; United States National Institutes of Health; Video Recording; arm; biobank; clinical phenotype; cohort; comorbidity; data dissemination; demographics; diagnostic biomarker; flexibility; healthy volunteer; inclusion criteria; interest; non-verbal; novel diagnostics; outcome prediction; patient population; prospective; recruit; social cognition; study population; tomography

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. In 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. We also added a remote samples group, for those participants who are interested in study participation, but are unable to travel to Bethesda, MD for the in-person arm of the study. The remote samples group will answer similar questions around their medical history and provide records if they choose, as well as send in their biospecimens for analysis. Moving forward, we continue to collect prospective data in our cohorts and plan future publications to present the longitudinal data for peer-review.

本研究于2010年3月17日获得CNS IRB Blue批准。研究团队人员配备齐全，我们正在积极招募本方案的患者。 2011年7月，我们获得了IRB对一项子研究的批准，该子研究将研究纳入标准扩大至损伤后5年。该子研究将主要集中于收集TBI通用数据元素（CDE）、血液和成像。 2012年6月，IRB批准将我们的入组年龄范围从18-70岁扩大到18岁及以上。在方案的成像章节中，相同的修正案将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求但获得社区资源有限的受试者的需求。 2014年底，IRB批准收集超高场（7特斯拉）成像参数，NMR中心每月分配时间。7 T磁体已用于扫描冲击波和非冲击波TBI患者，以确定是否可以在超高场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，增加健康志愿者对照组。此外，我们注意到，当地TBI患者群体不是正态分布的，他们的教育水平略高于平均水平。虽然与结果进行比较的规范性数据是经过人口统计学调整的，但与来自同一人群的对照组进行直接比较将为我们的研究结果提供支持。在方案的早期版本中，讨论了是否需要对照组。然而，在当地TBI人群的人口统计学已知并且健康对照可以与患者人群相匹配之前，决定推迟对对照组的研究。 将健康志愿者对照组纳入数据集可以与正常当地样本进行直接比较。因此，在同一台扫描仪上同时收集对照组与患者人群的成像数据将对本研究产生重大影响。在当地健康志愿者样本人群中收集相同的临床相关性，如在TBI人群中所做的那样，将在评估新的诊断成像和生物标志物技术时解决这一关键需求。在本研究的情况下，该对照人群可能需要与各种患者人口统计数据以及可能影响我们的成像或血清结果的任何合并症进行匹配。 评估语言、话语和社会认知的其他SLP措施已添加到方案中。话语措施将包括录音和/或录像。语篇分析是对程序性、叙述性、会话性和其他语篇任务中的语言和非语言行为的评估。将健康志愿者与年龄和性别相似的TBI患者配对，以比较患有和没有TBI的个体之间的话语测量。 前几年的修订增加了健康志愿者的入组，并增加了计划和进行方案评估的灵活性。NIH工作人员/雇员已被添加为潜在的研究参与者。根据FDA指南，增加了反映造影剂相关注意事项的语言。2022年，选择暴露（SEG）参与者的入组人数增加至96人。这些参与者，谁已被美国政府机构确定为潜在的暴露于非天然能源，与TBI生物学纵向研究。方案中还增加了听觉和前庭测试。此外，还将入组96例未受影响的匹配健康志愿者。从研究中删除了Postitron发射断层扫描。 在2022财年，我们修改了方案，从扫描中删除了造影剂，并进一步将SEG及其对照组的数量从96例增加到115例，这是由于我们被转诊的全球病例增加。此外，我们开始了初步的探索性分析，并正在准备数据以供分发。我们还增加了一个远程样本组，用于那些有兴趣参与研究，但无法前往马里兰州贝塞斯达参加研究的人。远程样本组将回答有关他们病史的类似问题，并提供记录（如果他们愿意），以及发送他们的生物样本进行分析。 展望未来，我们将继续收集队列中的前瞻性数据，并计划未来的出版物，以提供纵向数据供同行评审。

项目成果

Estimating premorbid intelligence in persons with traumatic brain injury: an examination of the Test of Premorbid Functioning.

评估创伤性脑损伤患者的病前智力：病前功能测试的检查。

• DOI: 10.1080/23279095.2019.1661247
• 发表时间: 2021
• 期刊: Applied neuropsychology. Adult
• 作者: Joseph,Annie-LoriC;Lippa,SaraM;McNally,ShannonM;Garcia,KatelynM;Leary,JacobB;Dsurney,John;Chan,Leighton
• 通讯作者: Chan,Leighton

How do you treat traumatic brain injury? One symptom at a time.

如何治疗脑外伤？

• DOI: 10.1002/ana.25529
• 发表时间: 2019
• 期刊: Annals of neurology
• 影响因子: 11.2
• 作者: Brody,DavidL;Chan,Leighton;Cizza,Giovanni
• 通讯作者: Cizza,Giovanni

Headaches in Traumatic Brain Injury: Improvement Over Time, Associations With Quality of Life, and Impact of Migraine-Type Headaches.

创伤性脑损伤中的头痛：随时间的推移而改善、与生活质量的关联以及偏头痛型头痛的影响。

• DOI: 10.1097/htr.0000000000000790
• 发表时间: 2023
• 期刊: The Journal of head trauma rehabilitation
• 作者: Flynn,Spencer;Moore,Brian;vanderMerwe,AndreJ;Moses,Anita;Lo,Jessica;Shahim,Pashtun;Chan,Leighton
• 通讯作者: Chan,Leighton