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

项目摘要/摘要 镰状细胞病是一种遗传性血液疾病，具有多种神经系统和发育性疾病。 并发症。特别是2至5岁患有SCD的幼儿，患上 缺血性中风和无症状脑梗塞(SCI)。脊髓损伤是高信号的T2脑磁共振 无急性神经系统症状但伴有相关损害的MRI病变 认知和未来进展性或额外卒中/脊髓损伤的风险增加。神经影像与神经认知 在学龄期和成年SCD人群中，与SCI相关的资料已经很好地建立了。此信息是 在6岁以下患有SCD的幼儿中，由于MRI有镇静/麻醉的风险，这种情况很少发生。 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，而不需要 通过先导性研究对患有SCD的3-4岁儿童进行镇静。 该应用程序的长期目标是开发一种诊断电池，该电池使用 未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的幼儿有患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 患有SCD的儿童从研究开始到研究结束。参与者还将在3点接受初步的神经成像电池 至4岁，在研究结束时重复进行神经成像，并在研究中进行纵向神经认知测试 入门，进行初始神经成像，以及出口神经成像。这一多学科、多模式的提案 有三个目标。目标1将确定3至4岁儿童的相关神经成像和神经认知表现 对SCD和SCI患儿进行初步MRI检查，并与无SCI的SCD患儿进行比较。目标2 将分析哪些神经成像指标、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的儿童在EXIT MRI上的纵向数据。《目标3》将探索 不同疾病调整治疗(慢性疾病)儿童神经影像测量的差异 输血疗法、羟基脲)，由其临床提供者通过二次数据分析确定。 这项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脊髓损伤， 导致了一项多点研究，以在更大的地区异质性SCD人群中验证这些发现。这个 研究派是一名神经发育内科医生，是NHLBI K23的首席研究员，非常适合扩展她 现有的研究队列得到了一组合作调查人员的支持，其中包括一名高级行为心理学家 和神经成像物理学家，以及现有的合作者和工作人员。

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.