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: 10470928
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470928
• 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 magnetic resonance imaging; 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.

项目总结/文摘