Cognitive and Neuroimaging Study in Sickle Cell Disease

镰状细胞病的认知和神经影像学研究

• 批准号: 6780503
• 负责人: ELIAS R MELHEM
• 金额: $ 44.77万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6780503
• 关键词: bioimaging /biomedical imaging; blood flow measurement; brain circulation; brain imaging /visualization /scanning; children; cognition disorders; developmental disease /disorder; developmental neurobiology; disease /disorder proneness /risk; human subject; infarct; longitudinal human study; magnetic resonance imaging; neuroanatomy; neuropsychological tests; neuropsychology; pathologic process; sickle cell anemia; ultrasound blood flow measurement

DESCRIPTION (provided by applicant): Many children with sickle cell disease (SCD) who have no history of overt stroke are still at risk for brain injury manifested by cognitive impairment, a major source of morbidity in this population. Unfortunately, conventional diagnostic methods, such as anatomical MRI, MRA and TCD are not sensitive for demonstrating the extent and severity of brain injury, and may be normal in the majority of those children. Thus there is a need for more sensitive diagnostic tools that can identify children at risk before onset of brain injury. In a subset of children with cognitive impairment, anatomical MRI may demonstrate silent infarctions, the pathogenesis of which is complex and remains speculative. Importantly, several studies have shown associations between extent of silent infarctions and severity of cognitive impairment. However, reports on associations between location of silent infarcts and type of cognitive dysfunction are less convincing and sometimes inconsistent. Possible reasons may be related to 1) use of anatomical MRI as the only surrogate marker for brain injury, 2) qualitative assignment of total lesion burden and spatial distribution in the brain, and 3) lack of longitudinal comparison of subjects. To address those issues we intend to 1) use advanced MRI-based techniques (perfusion and quantitative MRI for measuring T1-relaxation of brain parenchyma) specially designed to interrogate the microcirculation and microstructure of the brain in order to gain further insight into the pathogenesis of brain injury, 2) demonstrate that those advanced MRI-based techniques are sensitive predictors of subsequent increase in the volume of silent infarctions, and progressive decline in performance on neuropsychological tests, and 3) integrate cross sectional and longitudinal data into our computer-based Brain-Image Database (BRAID) so that we can more accurately quantify and map regional MRI-based abnormalities and better correlate with type of cognitive dysfunction. The results of this project will help identify risk factors for silent brain infarcts and cognitive decline in children with SCD, provide some insight into the pathogenesis of these silent infarcts, and improve our understanding of the relationship between the spatial distribution of MRI-based brain abnormalities and domain-specific brain dysfunction measured by tailored neuropsychological tests.

描述（由申请人提供）：许多没有公开中风病史的镰状细胞疾病（SCD）的儿童仍处于认知障碍表现出的脑损伤的风险，这是该人群中发病率的主要来源。 不幸的是，常规的诊断方法（例如解剖学MRI，MRA和TCD）对证明脑损伤的程度和严重程度并不敏感，并且在大多数儿童中可能是正常的。因此，需要更敏感的诊断工具，这些工具可以在脑损伤发作之前识别有风险的儿童。 在认知障碍的儿童的一部分中，解剖学MRI可能表现出沉默的梗塞，其发病机理很复杂，并且保持投机性。重要的是，一些研究表明，无声梗塞的程度与认知障碍的严重程度之间存在关联。但是，关于无声梗塞与认知功能障碍类型之间关联的报告不那么令人信服，有时不一致。可能的原因可能与1）使用解剖学MRI作为脑损伤的唯一替代标记，2）总病变负担和大脑中空间分布的定性分配，以及3）缺乏对受试者的纵向比较。 To address those issues we intend to 1) use advanced MRI-based techniques (perfusion and quantitative MRI for measuring T1-relaxation of brain parenchyma) specially designed to interrogate the microcirculation and microstructure of the brain in order to gain further insight into the pathogenesis of brain injury, 2) demonstrate that those advanced MRI-based techniques are sensitive predictors of subsequent increase in the volume of silent infarctions, and progressive decline in performance关于神经心理学测试，以及3）将横截面和纵向数据整合到我们的基于计算机的脑图像数据库（编织）中，以便我们可以更准确地量化和映射基于区域MRI的异常，并更好地与认知功能障碍类型更好地相关。 该项目的结果将有助于确定SCD儿童无声脑梗塞和认知能力下降的危险因素，提供对这些无声梗塞的发病机理的深入了解，并提高我们对基于MRI的大脑异常的空间分布与结构域特异性脑功能障碍之间的关系的理解。