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
基本信息
- 批准号:10281597
- 负责人:
- 金额:$ 8.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:12 year old3 year old4 year old5 year old6 year oldAcuteAdultAgeAnatomyAnesthesia proceduresAxonBehavioralBloodBrainBrain InjuriesBrain-Derived Neurotrophic FactorCase-Control StudiesCerebral InfarctionCerebrovascular CirculationCerebrumCharacteristicsChildChronicClinicalClinical DataCognitiveCohort StudiesCollectionDataData AnalysesData CollectionDevelopmentDiagnosisDiagnosticDiseaseEarly treatmentEducational InterventionEnzyme-Linked Immunosorbent AssayFundingFutureGoalsGuidelinesHematological DiseaseImpaired cognitionInflammatoryInheritedInjuryIntelligenceIschemic StrokeKnowledgeLanguageLeadLesionLiteratureLongitudinal StudiesMagnetic Resonance ImagingMeasuresMedicalMedical HistoryMetabolicNational Heart, Lung, and Blood InstituteNeurocognitiveNeurodevelopmental DisorderNeurologicNeurologic ExaminationNeurologic SymptomsNeuronsOutcomeOxygenParticipantPerformancePhysiciansPhysiologicalPilot ProjectsPlasmaPlasma ProteinsPopulationPrincipal InvestigatorProteinsProviderPsychologistRecurrenceResearchResearch PersonnelRiskSamplingSchool-Age PopulationSedation procedureSensitivity and SpecificitySickle Cell AnemiaSiteStrokeTestingTimeTrainingTransfusionVulnerable PopulationsWorkbasebrain tissueclinical carecohortexecutive functionexperiencehigh riskhydroxyureaimprovedminimal riskmultidisciplinarymultimodalityneurocognitive testneurograninneuroimagingpreventprospectiveprotein biomarkersscreeningskillsstroke risktreatment grouptrend
项目摘要
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/摘要
镰状细胞病(SCD)是一种遗传性血液病,具有几种神经和发育障碍。
并发症特别是2至5岁的SCD幼儿,
缺血性中风和无症状性脑梗塞(SCI)。SCI是高信号T2脑磁共振
无伴随急性神经系统症状但伴有相关损害的MRI病变
认知和未来进行性或额外卒中/SCI的风险增加。神经成像和神经认知
与SCI相关的特征在学龄和成人SCD人群中已得到很好的确立。该信息
由于MRI的镇静/麻醉风险,在6岁以下患有SCD的幼儿中基本未知。
我们的初步研究表明,行为训练可以产生高质量的神经成像数据,
通过初步研究,对3至4岁SCD儿童进行镇静。
本申请的长期目标是开发一种使用以下组合的诊断电池:
未使用镇静剂的神经成像测量、神经认知测试和血浆脑损伤蛋白水平,以确定
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,
从研究入组到研究退出的SCD儿童。参与者还将在3点接受初始神经影像学检查
至4岁,在研究退出时重复神经影像学检查以及在研究时进行纵向神经认知测试
入路、初始神经成像和出路神经成像。这一多学科、多模式的建议
有三个目标。目的1将确定3至4岁儿童的相关神经影像学和神经认知表现
通过将SCD和SCI儿童的结果与SCD无SCI儿童的结果进行比较。目的2
将分析哪些神经影像学指标、神经认知测试分数和血浆蛋白水平可以预测
未来脊髓损伤风险,比较有脊髓损伤和无脊髓损伤儿童的MRI纵向数据。Aim 3将探索
不同疾病缓解治疗(慢性)的儿童神经影像学指标的差异
输血治疗,羟基脲),由其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成像测量和神经认知测试可以预测SCI,
从而导致多中心研究以在更大的区域异质性SCD群体中验证这些发现。的
研究PI,神经发育医生,是NHLBI K23的主要研究者,非常适合扩大她的研究领域。
现有的研究队列,由一组合作研究者提供支持,包括一名高级行为心理学家
和神经影像物理学家,以及现有的合作者和工作人员。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('EBONI I LANCE', 18)}}的其他基金
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 - 财政年份:2023
- 资助金额:
$ 8.1万 - 项目类别:
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 - 财政年份:2021
- 资助金额:
$ 8.1万 - 项目类别:
Clinical and Neuroimaging Phenotypes of Neurodevelopmental Disorders inPediatric Sickle Cell Disease
小儿镰状细胞病神经发育障碍的临床和神经影像表型
- 批准号:
9385561 - 财政年份:2017
- 资助金额:
$ 8.1万 - 项目类别:
Clinical and Neuroimaging Phenotypes of Neurodevelopmental Disorders inPediatric Sickle Cell Disease
小儿镰状细胞病神经发育障碍的临床和神经影像表型
- 批准号:
9539716 - 财政年份:2017
- 资助金额:
$ 8.1万 - 项目类别:
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