Improved Diagnostics & Advanced Magnetic Resonance Imaging for Pediatric NPSLE

改进的诊断

• 批准号: 8382398
• 负责人: Hermine I Brunner
• 金额: $ 24.66万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8382398
• 关键词: Adult; Affect; Attention; Awareness; Behavior; Biological Markers; Biological Markers; Boxing; Brain; Child; Child Behavior Checklist; Child Development; Childhood; Clinic; Clinical; Clinical Investigator; Clinical Research; 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; Goals; Grant; Growth; Image; Imaging Techniques; Investigation; Knowledge; Magnetic Resonance Imaging; Measurement; Measures; Metric; Molecular; Morbidity - disease rate; National Institute of Arthritis and Musculoskeletal and Skin Diseases; 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; Reporting; Research; Research Personnel; Screening procedure; Self-Administered; Short-Term Memory; Speed; Study Subject; Surrogate Markers; Systemic Lupus Erythematosus; Testing; Time; United States National Institutes of Health; Validation; Work; base; cognitive function; effective therapy; executive function; gray matter; improved; innovation; mortality; multidisciplinary; 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。在理解这些机制的基础上存在着一个根本性的差距。 儿童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），没有有效的筛查工具来帮助诊断儿童NCD 儿科SLE（pSLE）。这是一个重要的问题，因为NCD在患有 pSLE，通常导致注意力、视觉建构能力和工作记忆的普遍下降。的 我们研究的长期目标是通过更好的循证医学证据， 治疗。该应用程序的目标是为非传染性疾病提供一个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，以提高我们的理解， pSLE影响中枢神经系统并引起NCD。待检验的中心假设是pSLE是 与认知发育受损相关，这反映在灰质功能的变化上， 功能性磁共振成像（fMRI），弥散成像显示白色脑物质束改变 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， 小儿神经心理学自动评估量表（Ped-ANAM）具有上级测量功能 与其他可用的自填问卷相比， 行为、认知和执行功能的影响。在强有力的初步数据的指导下，这些假设将 通过追求以下具体目标进行测试：1）将Ped-ANAM作为认知功能的测量， 使用正式的神经心理学测试作为标准2）评估pSLE对 根据正式的神经心理学测试和Ped-ANAM 3a） 使用功能磁共振成像来识别参与注意力、视觉建构能力的认知网络的灰质元件 3 b）使用DTI估计所涉及的白色物质变化 在注意力、视觉建构能力和工作记忆中，pSLE对这些能力的影响最大。40例pSLE受试者 和40个匹配的“最好的朋友”对照将使用Ped-ANAM和其他验证的研究1.5年 神经心理学测试将进行高级成像（fMRI，DTI），重点关注两个最常见的 受pSLE影响的神经认知领域。这项研究是创新的，因为没有 临床医生或研究人员可以使用的pSLE相关NCD的有效筛查工具，以及 导致NCD的机制和pSLE对发育中的大脑的具体作用仍然难以捉摸。的 预期的结果是，我们将确定灰质神经元回路和白色物质束， 与pSLE相关的NCD相关，Ped-ANAM的前瞻性验证将容易产生 pSLE相关NCD的可用筛选工具。 与公共卫生的相关性：这是一个重要的调查领域， 增加患者发病率和死亡率，降低患者生活质量。更好的诊断测试和 关于NCD病因学的知识是未来开发靶向疗法的基础， pSLE儿童患者，也可能用于SLE成人患者。