Improved Diagnostics & Advanced Magnetic Resonance Imaging for Pediatric NPSLE

项目总结。在理解潜在的机制方面存在着根本性的差距 儿童神经精神性系统性红斑狼疮(PNPSLE)的进展 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NCD儿童 儿童系统性红斑狼疮(PSLE)是可用的。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，通常会导致注意力、视觉建构能力和工作记忆的普遍下降。这个 我们研究的长期目标是通过更好的循证证据来改善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一个简单易用的筛查工具 在常规的临床环境中使用，并使用先进的成像技术来提高我们对 PSLE影响中枢神经系统，导致NCD。需要检验的中心假设是pSLE是 与认知发育受损有关，表现为大脑灰质功能的改变。 功能磁共振成像(FMRI)，弥漫性脑白质束改变 张量成像(DTI)，并经正式神经心理测试证实。此外，我们假设 儿科自动化神经心理评估指标(Ped-ANAM)具有优越的测量能力 与其他可用的自填式问卷相比，早期发现pSLE相关NCD的特性 行为、认知和执行功能。在强劲的初步数据的指导下，这些假设将是 通过追求以下具体目标进行测试：1)验证Ped-ANAM作为认知功能的测量工具 以正式的神经心理测试为标准2)评估pSLE对 基于正式神经心理测试和Ped-ANAM 3a的儿童认知发展 使用功能磁共振成像识别认知网络中与注意力、视觉建构能力有关的灰质元素 &受pSLE影响最大的工作记忆；以及3b)使用DTI估计涉及的脑白质变化 在注意力方面，受pSLE影响最大的是视觉建构能力和工作记忆。40名pSLE受试者 使用Ped-ANAM和其他经验证的方法对40名匹配的“最好的朋友”对照进行为期1.5年的研究 神经心理测试。将进行高级成像(fMRI、DTI)，重点关注这两种最常见的 受pSLE影响的神经认知域。这项拟议的研究具有创新性，因为没有 可供临床医生或研究人员使用的pSLE相关NCD的有效筛查工具，以及 导致NCD的机制和pSLE对发育中大脑的具体影响仍然难以捉摸。这个 预期的结果是，我们将识别出灰质神经元回路和白质束 与pSLE相关的NCD相关，Ped-ANAM的预期验证将容易地产生 可用于pSLE相关NCD的筛查工具。 与公共卫生的相关性：与pNPSLE一样，这是一个重要而未被调查的领域 加重患者的发病率和死亡率，降低患者的生活质量。更好的诊断测试和 对NCD病因学的了解是未来开发针对NCD的靶向治疗的基础 患有pSLE的儿童，也可能用于患有SLE的成人。

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.