Neuroimaging and Neurocognitive 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和神经认知标志物

• 批准号: 10636709
• 负责人: EBONI I LANCE
• 金额: $ 37.33万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636709
• 关键词: 3 year old; 4 year old; 5 year old; 6 year old; Acute; Adult; Age; Anesthesia procedures; Axon; Behavioral; Blood; Brain Injuries; Case/Control Studies; Cephalic; Cerebral Infarction; Cerebrovascular Circulation; Cerebrum; Characteristics; Child; Chronic Disease; Clinical; Clinical Data; Cognition; Cognitive; Cohort Studies; Collection; Data; Data Collection; Development; Diagnosis; Diagnostic; Disease; Early identification; Early treatment; Education; Enzyme-Linked Immunosorbent Assay; Evaluation; Fetal Hemoglobin; Future; Goals; Guidelines; Hematological Disease; Hemoglobin concentration result; Impaired cognition; Inflammatory; Inherited; Injury; Intelligence; Ischemic Stroke; Knowledge; Language; Lesion; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Mathematics; Measures; Medical; Medical History; Metabolic; Metabolic stress; Metabolism; Morbidity - disease rate; Neurocognitive; Neurodevelopmental Deficit; Neurologic; Neurologic Examination; Neurologic Symptoms; Neurons; Neuropsychological Tests; Outcome; Oxygen; Participant; Patients; Performance; Physical Function; Physicians; Pilot Projects; Plasma; Plasma Proteins; Population; Proteins; Psychologist; Reading; Recommendation; Recording of previous events; Recurrence; Research; Research Personnel; Risk; Risk Factors; Sample Size; Sampling; School-Age Population; Sedation procedure; Sensitivity and Specificity; Services; Sickle Cell Anemia; Site; Stroke; Test Result; Testing; Therapeutic Intervention; Time; Training; Vulnerable Populations; White Blood Cell Count procedure; Work; brain magnetic resonance imaging; brain tissue; disability; executive function; experience; high risk; hydroxyurea; improved; male; minimal risk; multidisciplinary; multimodality; neurocognitive test; neuroimaging; neuroprotection; predictive marker; prevent; prospective; risk prediction; screening; sex; skills; standard of care; verbal

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 two Aims. Aim 1 will identify the cross-sectional 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 compare longitudinal data from 6 year-old children with and without SCI on exit MRI. Exploratory aims will explore differences in the neuroimaging measures in children on different disease-modifying treatments (hydroxyurea) and plasma protein levels in children with and without SCI. 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 early stage 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.

项目摘要/摘要 镰状细胞病（SCD）是一种遗传性血液疾病，有几种神经和发育 并发症。尤其是2至5岁的SCD的幼儿有增加的风险 缺血性中风和无声的脑梗塞（SCI）。 SCI是超强度T2脑磁共振 成像（MRI）病变没有伴有急性神经系统症状，但相关障碍 认知和未来进步或其他中风/SCI的风险增加。神经影像学和神经认知 与SCI相关的概况已在学龄和成人SCD人群中建立。此信息是 在6岁以下的幼儿患有SCD的幼儿由于镇静/MRI麻醉的风险，这在很大程度上未知。 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学数据 通过试点研究，有3至4岁儿童患有SCD的儿童的镇静。 该应用程序的长期目标是使用组合来开发诊断电池 未培养的神经影像学措施，神经认知测试和血浆脑损伤蛋白水平鉴定 SCD有SCI风险的幼儿。通过一项前瞻性纵向病例对照研究，我们将收集 病史和临床数据并进行神经系统检查和血液每年100 从研究进入到研究退出的SCD的儿童。参与者还将在3时进行初始神经影像电池 在研究出口时重复神经影像以及研究的纵向神经认知测试，在研究中重复神经影像学检查 进入，具有初始神经影像，并带有出口神经影像。这个多学科和多模式的建议 有两个目标。 AIM 1将确定3至4年的横断面神经影像学和神经认知发现 初始MRI的SCD和SCI的老孩子将其结果与无SCI的儿童进行比较。目的 2将比较来自有或没有SCI的6岁儿童出口MRI的纵向数据。探索目的 将探索不同疾病改良治疗的儿童神经影像措施的差异 （羟基脲）和患有SCI儿童的血浆蛋白水平。拟议的工作将决定 哪些神经影像学措施和神经认知测试可能会预测SCI，从而导致多站点研究 在较大的区域异质SCD种群中验证这些发现。研究pi，一个 神经发育医师是一名早期研究员，非常适合扩大她现有的研究队列 在一个共同评估者团队的支持下，包括高级行为心理学家和神经影像学 物理学家以及现有的合作者和员工。