Neuroimaging, Neurocognitive, and Plasma Protein Markers of Brain Injury in Young Children with Sickle Cell Disease

镰状细胞病幼儿脑损伤的神经影像学、神经认知和血浆蛋白标志物

• 批准号: 10281597
• 负责人: EBONI I LANCE
• 金额: $ 8.1万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10281597
• 关键词: 12 year old; 3 year old; 4 year old; 5 year old; 6 year old; Acute; Adult; Age; Anatomy; Anesthesia procedures; Axon; Behavioral; Blood; Brain; Brain Injuries; Brain-Derived Neurotrophic Factor; Case-Control Studies; Cerebral Infarction; Cerebrovascular Circulation; Cerebrum; Characteristics; Child; Chronic; Clinical; Clinical Data; Cognitive; Cohort Studies; Collection; Data; Data Analyses; Data Collection; Development; Diagnosis; Diagnostic; Disease; Early treatment; Educational Intervention; Enzyme-Linked Immunosorbent Assay; Funding; Future; Goals; Guidelines; Hematological Disease; Impaired cognition; Inflammatory; Inherited; Injury; Intelligence; Ischemic Stroke; Knowledge; Language; Lead; Lesion; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medical; Medical History; Metabolic; National Heart, Lung, and Blood Institute; Neurocognitive; Neurodevelopmental Disorder; Neurologic; Neurologic Examination; Neurologic Symptoms; Neurons; Outcome; Oxygen; Participant; Performance; Physicians; Physiological; Pilot Projects; Plasma; Plasma Proteins; Population; Principal Investigator; Proteins; Provider; Psychologist; Recurrence; Research; Research Personnel; Risk; Sampling; School-Age Population; Sedation procedure; Sensitivity and Specificity; Sickle Cell Anemia; Site; Stroke; Testing; Time; Training; Transfusion; Vulnerable Populations; Work; base; brain tissue; clinical care; cohort; executive function; experience; high risk; hydroxyurea; improved; minimal risk; multidisciplinary; multimodality; neurocognitive test; neurogranin; neuroimaging; prevent; prospective; protein biomarkers; screening; skills; stroke risk; treatment group; trend

Project Summary/Abstract Sickle cell disease (SCD) is an inherited blood disorder with several neurological and developmental complications. Young children with SCD between 2 and 5 years of age, in particular, have an increased risk for ischemic stroke and silent cerebral infarctions (SCI). SCI are hyperintense T2 brain magnetic resonance imaging (MRI) lesions with no accompanying acute neurological symptoms but with associated impaired cognition and increased risk of future progressive or additional stroke/SCI. Neuroimaging and neurocognitive profiles associated with SCI are well established in school-aged and adult SCD populations. This information is largely unknown in young children under 6 years of age with SCD due to risk of sedation/anesthesia with MRI. Our preliminary studies have shown that behavioral training can yield high quality neuroimaging data without sedation in 3 to 4 years old children with SCD through a pilot study. The long term goal of this application is to develop a diagnostic battery using a combination of unsedated neuroimaging measures, neurocognitive testing, and plasma brain injury protein levels to identify young children with SCD at risk for SCI. Through a prospective longitudinal case-control study, we will collect medical history and clinical data and perform neurological examination and blood draws annually in 100 children with SCD from study entry to study exit. Participants will also undergo initial neuroimaging battery at 3 to 4 years of age with repeat neuroimaging at study exit as well as longitudinal neurocognitive testing at study entry, with initial neuroimaging, and with exit neuroimaging. This multi-disciplinary and multi-modality proposal has three Aims. Aim 1 will identify the associated neuroimaging and neurocognitive findings in 3 to 4 year-old children with SCD and SCI on initial MRI by comparing their results to children with SCD without SCI. Aim 2 will analyze which neuroimaging measures, neurocognitive test scores, and plasma protein levels may predict future SCI risk, comparing longitudinal data from children with and without SCI on exit MRI. Aim 3 will explore differences in the neuroimaging measures in children on different disease-modifying treatments (chronic transfusion therapy, hydroxyurea) as determined by their clinical providers, through a secondary data analysis. The proposed work will determine which neuroimaging measures and neurocognitive testing may predict SCI, leading to a multi-site study to validate these findings in a larger regionally heterogenous SCD population. The study PI, a neurodevelopmental physician, is an NHLBI K23 principal investigator well suited to expand her existing study cohort with support from a team of co-investigators, including a senior behavioral psychologist and neuroimaging physicist, as well as existing collaborators and staff.

项目概要/摘要 镰状细胞病 (SCD) 是一种遗传性血液疾病，伴有多种神经和发育障碍 并发症。尤其是 2 至 5 岁患有 SCD 的幼儿，罹患 SCD 的风险更高 缺血性中风和无症状脑梗塞（SCI）。 SCI 是高信号 T2 脑磁共振 不伴有急性神经系统症状但伴有相关受损的影像学 (MRI) 病变 认知和未来进行性或额外中风/SCI 的风险增加。神经影像学和神经认知 与 SCI 相关的概况在学龄和成人 SCD 人群中已得到很好的确立。该信息是 由于 MRI 镇静/麻醉的风险，对于患有 SCD 的 6 岁以下幼儿来说，这一点在很大程度上是未知的。 我们的初步研究表明，行为训练可以产生高质量的神经影像数据，而无需 通过一项试点研究对患有 SCD 的 3 至 4 岁儿童进行镇静。 该应用的长期目标是开发一种结合使用的诊断电池 未镇静的神经影像学测量、神经认知测试和血浆脑损伤蛋白水平来识别 患有 SCD 的幼儿有发生 SCI 的风险。通过前瞻性纵向病例对照研究，我们将收集 病史和临床数据，每年进行神经系统检查和抽血 100 患有 SCD 的儿童从入学到毕业。参与者还将在 3 点接受初始神经影像检查 至 4 岁，在研究退出时重复进行神经影像检查以及在研究时进行纵向神经认知测试 入口、初始神经影像和出口神经影像。这项多学科、多模式的提案 有三个目标。目标 1 将确定 3 至 4 岁儿童的相关神经影像学和神经认知发现 通过将 SCD 和 SCI 儿童的初始 MRI 结果与没有 SCI 的 SCD 儿童进行比较。目标2 将分析哪些神经影像学测量、神经认知测试分数和血浆蛋白水平可以预测 未来 SCI 风险，比较有和没有 SCI 儿童退出 MRI 的纵向数据。目标3将探索 接受不同疾病缓解治疗（慢性病）的儿童的神经影像学测量差异 输血疗法（羟基脲）由临床提供者通过二次数据分析确定。 拟议的工作将确定哪些神经影像学测量和神经认知测试可以预测 SCI、 开展了一项多中心研究，以在更大的区域异质性 SCD 人群中验证这些发现。这 研究 PI 是一名神经发育医师，也是 NHLBI K23 首席研究员，非常适合扩展她的研究 现有的研究队列得到了包括一名高级行为心理学家在内的联合研究人员团队的支持 和神经影像物理学家，以及现有的合作者和工作人员。