Improved Diagnostics & Advanced Magnetic Resonance Imaging for Pediatric NPSLE

改进的诊断

• 批准号: 7475983
• 负责人: Hermine I Brunner
• 金额: $ 26.55万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475983
• 关键词: Adult; Affect; Attention; Awareness; Behavior; Biological; Biological Markers; Boxing; Brain; Child; Child Behavior; Child Development; Childhood; Clinic; Clinical; Clinical Investigator; Cognition; Cognitive; Control Groups; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Diffusion Magnetic Resonance Imaging; Early Diagnosis; Elements; Equipment and supply inventories; Evidence based treatment; Foundations; Friends; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Glass; Goals; Grant; Growth; Image; Imaging Techniques; Investigation; Knowledge; Magnetic Resonance Imaging; Measurement; Measures; Metric; Molecular; Morbidity - disease rate; Neuraxis; Neurocognitive; Neurocognitive Deficit; Neurons; Neuropsychiatric Systemic Lupus Erythematosus; Neuropsychological Tests; Parents; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Principal Investigator; Property; Public Health; Quality of life; Questionnaires; Rate; Reporting; Research; Research Personnel; Screening procedure; Self-Administered; Short-Term Memory; Speed; Standards of Weights and Measures; Study Subject; Surrogate Markers; Systemic Lupus Erythematosus; Testing; Time; Validation; Work; base; cognitive function; executive function; gray matter; improved; innovation; mortality; neuronal circuitry; neuropsychological; outcome forecast; programs; prospective; skills; tool; white matter; white matter change

PROJECT SUMMARY. There is a fundamental gap in understanding the mechanisms underlying the development of pediatric neuropsychiatric systemic lupus erythematosus (pNPSLE), especially pertaining to neurocognitive dysfunction (NCD), and no effective screening tools to help diagnose NCD in children with pediatric SLE (pSLE) are available. This is an important problem because NCD is common among children with pSLE, often resulting in a pervasive decline in attention, visuoconstructional ability and working memory. The long-term goal of our research is to improve the prognosis of children with pSLE through better evidence-based treatments. The objectives of this application are to make an easy-to-use screening tool for NCD available for use in routine clinic settings and to employ advanced imaging techniques to heighten our understanding in how pSLE affects the central nervous system and causes NCD. The central hypotheses to be tested are that pSLE is associated with impaired cognitive growth as reflected by changes in the grey matter functioning detected by functional magnetic resonance imaging (fMRI), alterations of white brain matter tracts seen with Diffusion Tensor Imaging (DTI), and confirmed by formal neuropsychological testing. Additionally, we hypothesize that the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) has superior measurement properties for the early detection of pSLE-associated NCD over other available self-administered questionnaires of behavior, cognition and executive functioning. Guided by strong preliminary data, these hypotheses will be tested by pursuing the following specific aims: 1) Validate the Ped-ANAM as a measure of cognitive function in pSLE using formal neuropsychological testing as the criterion standard 2) Assess the effects of pSLE on cognitive development during childhood based on formal neuropsychological testing and the Ped-ANAM 3a) Use fMRI to identify grey matter elements of cognitive networks involved in attention, visuoconstructional ability & working memory that are most affected by pSLE; and 3b) Use DTI to estimate white matter changes involved in attention, visuoconstructional ability & working memory that are most affected by pSLE. Forty pSLE subjects and 40 matched 'best-friend' controls will be studied for 1.5 years using the Ped-ANAM and other validated neuropsychological tests. Advanced imaging will be done (fMRI, DTI) with focus on the two most commonly affected neurocognitive domains afflicted by pSLE. The proposed research is innovative, because there are no effective screening tools for pSLE-associated NCD that can be used by clinicians or researchers, and mechanisms leading to NCD and the specific effects of pSLE on the developing brain remain elusive. The expected results are that we will identify grey matter neuronal circuitries and white matter tracts that are associated with pSLE-associated NCD and that the prospective validation of the Ped-ANAM will yield a readily usable screening tool for pSLE-associated NCD. Relevance to Public Health: This is an important and underinvestigated field of investigation as pNPSLE worsens patient morbidity and mortality and decreases patient quality of life. Better diagnostic tests and knowledge about the pathoetiology of NCD is the basis for the future development of targeted therapies for children with pSLE and can likely also be used for adults with SLE.

项目摘要。在理解其背后的机制方面存在根本差距 小儿神经精神系统性红斑狼疮 (pNPSLE) 的发展，特别是与 神经认知功能障碍 (NCD)，并且没有有效的筛查工具来帮助诊断患有神经认知功能障碍 (NCD) 的儿童 儿科系统性红斑狼疮 (pSLE) 可供选择。这是一个重要的问题，因为非传染性疾病在患有以下疾病的儿童中很常见 pSLE，通常导致注意力、视觉建构能力和工作记忆普遍下降。这 我们研究的长期目标是通过更好的基于证据的方法来改善 pSLE 儿童的预后 治疗。该应用程序的目标是为非传染性疾病提供易于使用的筛查工具 在常规临床环境中使用并采用先进的成像技术来加深我们对如何 pSLE 影响中枢神经系统并导致非传染性疾病 (NCD)。要检验的中心假设是 pSLE 是 与认知生长受损有关，这反映在灰质功能的变化上 功能磁共振成像（fMRI），弥散观察到的白脑质束的改变 张量成像（DTI），并通过正式的神经心理学测试证实。此外，我们假设 儿科自动神经心理评估指标 (Ped-ANAM) 具有卓越的测量效果 与其他可用的自填问卷相比，具有早期发现 pSLE 相关非传染性疾病的特性 行为、认知和执行功能。在强有力的初步数据的指导下，这些假设将被 通过追求以下具体目标进行测试： 1) 验证 Ped-ANAM 作为认知功能的衡量标准 pSLE 使用正式的神经心理学测试作为判定标准 2) 评估 pSLE 对 基于正式神经心理学测试和 Ped-ANAM 3a) 的儿童时期认知发展 使用功能磁共振成像来识别与注意力、视觉建构能力相关的认知网络的灰质元素 & 受 pSLE 影响最大的工作记忆； 3b) 使用 DTI 估计所涉及的白质变化 注意力、视觉建构能力和工作记忆受 pSLE 影响最大。四十个 pSLE 科目 40 个匹配的“最好的朋友”对照将使用 Ped-ANAM 和其他经过验证的方法进行为期 1.5 年的研究 神经心理学测试。将进行高级成像（fMRI、DTI），重点关注两种最常见的成像 受 pSLE 影响的神经认知域。所提出的研究具有创新性，因为没有 可供临床医生或研究人员使用的 pSLE 相关非传染性疾病的有效筛查工具，以及 导致 NCD 的机制以及 pSLE 对发育中的大脑的具体影响仍然难以捉摸。这 预期的结果是我们将识别灰质神经元回路和白质束 与 pSLE 相关的 NCD 相关，并且 Ped-AAM 的前瞻性验证将很容易产生一个 pSLE 相关非传染性疾病的可用筛查工具。 与公共卫生的相关性：与 pNPSLE 一样，这是一个重要且未经充分调查的研究领域 使患者的发病率和死亡率恶化，并降低患者的生活质量。更好的诊断测试和 对非传染性疾病病理学的了解是未来开发靶向治疗的基础 患有 pSLE 的儿童，也可能用于患有 SLE 的成人。