BRAIN CONECTIONS: ADD-ON STUDY OF SERIAL BRAIN MRIS EVERY SIX MONTHS

大脑连接：每六个月进行一次连续脑 MRI 附加研究

• 批准号: 7378915
• 负责人: MICHELLE A PETRI
• 金额: $ 0.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378915
• 关键词: BRAIN; CONECTIONS; ADD; STUDY; SERIAL

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Brain CONECTIONS: Add-on Study of Serial Brain MRIs Every Six Months ABSTRACT (Annual Report 12/01/2004 - 11/30/2005) Background: Neuropsychaitric SLE (NPSLE) occurs in 50-75% of SLE patients, depending on the sampling procedures and diagnostic criteria used and is a major source of morbidity and decreased quality of life. If cognitive function is carefully evaluated with sensitive neuropsychological testing, an even larger number of patients may have SLE-related neurologic involvement. SLE-related neurologic involvement encompasses a wide spectrum of overt neurologic and psychiatric features ranging from strokes, seizures, peripheral neuropathy, chorea, dementia, anxiety, and depression to more subtle cognitive abnormalities such as attention, memory, and visio-spatial abnormalities. Brain imaging is a powerful tool to noninvasively identify and differentiate the pathophysiological mechanisms responsible for NPSLE syndromes. Alone or in combination, anatomic Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) are the most widely used brain imaging techniques to study patients with NPSLE syndromes. Inconsistencies in the literature regarding the sensitivity and specificity of these techniques likely reflect inclusion of SLE patients with heterogeneous clinical presentations caused by different underlying pathophysiological mechanisms. Brain CONECTIONS is an NIH-funded ongoing, prospective, observational multi-center cohort study of cognitive function in newly-diagnosed patients with SLE. Brain MRI and PET are done at baseline, at year 3, and if there is an important decline in cognitive functioning on the ANAM, an automated battery of tests. Rationale: Analyses of 31 baseline brain MRI scans done to date among the participants of Brain CONECTIONS study found a surprising frequency of brain atrophy: 26% of patients had mild brain atrophy and 26% had moderate brain atrophy. This recent imaging findings from the Brain CONECTIONS study suggest the following: 1) newly diagnosed SLE patients have a high frequency of anatomic brain MRI abnormalities, 2) MRI abnormalities are associated with decreased sustained attention and reaction time and higher disease activity at study entry. This suggests that both functional and structural damage to the brain is evident early in the disease process and underscores the critical need to understand the underlying mechanism of brain involvement in SLE. "Brain CONECTIONS: Add-on Study of Serial Brain MRIs Every Six Months" allows brain MRIs to be done every 6 months, to find associates and predictors of brain atrophy irrespective of major change in cognitive functioning. Study questions and Specific aim: One: Determine the frequency of and potential reversibility or worsening of brain atrophy at baseline AND at 6 monthly follow-up. Two: Determine if atrophy is associated with clinical activity, as measured by clinical disease indices or serologic assays including low complements, high anti-DNA, and antiphospholipid antibodies. Three: Determine whether SLE treatment (determined by activity in other organs) affects brain atrophy: does prednisone worsens brain atrophy? Study Design: This is a pilot study designed to ascertain whether brain atrophy in SLE patients is progressive, stable, or reversible. In addition, we will explore demographic and clinical characteristics that may be associated with or predictive of brain atrophy. Neuro Image Acquisition Anatomic MRI image scanning are done every six months for the time that the patient has remaining in the Brain CONECTIONS study. As the prevalence of atrophy was so high at baseline, we feel it is important to follow subjects at six month intervals to determine if the atrophy is reversible and if it is associated with clinical activity. Anatomical MRI scans will include a T1- weighted, a T2- weighted, a proton density-weighted, and a 3D Gradient Recalled Acquisitions. Image reading will be performed on images displayed on screen monitors. All MRI images will be in DICOM 3 format. Controls are always included, in a blinded fashion, in the reading sessions at the University of Texas, San Antonio. Male controls are available. Dr. Brey and Dr. Fox (neurologist and neuroradiologist) are the principal readers. For patients, we record psychiatric illness. For qualitative analyses, images obtained from the brain MRI scans will be displayed on a screen using computer projection in a blinded fashion. Images will be projected in random order and will be read by consensus by the neurologists at the University of Texas, San Antonio. The rating for the MRI are: 0 = Normal, 1 = Mild atrophy, 2 = Moderate atrophy, any focal lesion, 3 = Severe atrophy, >5 focal lesions. Study Population: All Brain CONECTIONS patients entered at Hopkins are eligible for this add-on study. Outcome Measures: The primary outcome is the rating scale of 0, 1 (Mild), 2 (Moderate), and 3 (Severe). Current enrollment (12/01/2004 - 11/30/2005): 31 patients already completed the 1st Brain MRI of the add-on study of which 18 patients also completed the 6 month follow-up MRI.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。脑连接：每六个月进行一次连续脑 MRI 附加研究 摘要（年度报告 12/01/2004 - 11/30/2005） 背景：神经精神系统性红斑狼疮 (NPSLE) 发生在 50-75% 的系统性红斑狼疮患者中，具体取决于所使用的采样程序和诊断标准，并且是发病率和生活质量下降的主要根源。如果通过敏感的神经心理学测试仔细评估认知功能，则更多的患者可能患有与 SLE 相关的神经系统受累。 SLE 相关的神经系统受累涵盖广泛的明显神经和精神特征，从中风、癫痫、周围神经病变、舞蹈症、痴呆、焦虑和抑郁到更微妙的认知异常，如注意力、记忆力和视觉空间异常。 脑成像是一种强大的工具，可以无创地识别和区分 NPSLE 综合征的病理生理机制。单独或组合使用 2-[18F]氟-2-脱氧-D-葡萄糖 (FDG) 的解剖磁共振成像 (MRI) 和正电子发射断层扫描 (PET) 是研究 NPSLE 综合征患者最广泛使用的脑成像技术。文献中关于这些技术的敏感性和特异性的不一致可能反映出纳入了由不同的潜在病理生理机制引起的具有异质临床表现的 SLE 患者。 Brain CONECTIONS 是一项由 NIH 资助的持续性、前瞻性、观察性多中心队列研究，研究新诊断的 SLE 患者的认知功能。脑 MRI 和 PET 在基线、第三年进行，如果 ANAM（一组自动测试）认知功能显着下降，则进行。理由：对 Brain CONECTIONS 研究参与者迄今为止进行的 31 次基线脑 MRI 扫描的分析发现，脑萎缩的频率令人惊讶：26% 的患者患有轻度脑萎缩，26% 的患者患有中度脑萎缩。 Brain CONECTIONS 研究的最新影像学结果表明：1) 新诊断的 SLE 患者具有较高的解剖脑 MRI 异常频率，2) MRI 异常与持续注意力和反应时间减少以及研究开始时较高的疾病活动性相关。这表明大脑的功能和结构损伤在疾病过程的早期就很明显，并强调了了解 SLE 大脑参与的潜在机制的迫切需要。 “大脑连接：每六个月进行一次连续脑 MRI 的附加研究”允许每 6 个月进行一次脑 MRI，以发现脑萎缩的关联因素和预测因素，无论认知功能是否发生重大变化。研究问题和具体目标： 一：确定基线和 6 个月随访时脑萎缩的频率和潜在可逆性或恶化。 二：确定萎缩是否与临床活动相关，通过临床疾病指数或血清学检测（包括低补体、高抗 DNA 和抗磷脂抗体）来测量。 三：确定SLE治疗（由其他器官的活动决定）是否影响脑萎缩：泼尼松是否会加重脑萎缩？研究设计：这是一项试点研究，旨在确定 SLE 患者的脑萎缩是进行性的、稳定的还是可逆的。此外，我们将探讨可能与脑萎缩相关或可预测脑萎缩的人口统计学和临床​​特征。神经图像采集 在患者参与 Brain CONECTIONS 研究期间，每六个月进行一次解剖 MRI 图像扫描。由于基线时萎缩的患病率如此之高，我们认为每隔六个月对受试者进行一次随访以确定萎缩是否可逆以及是否与临床活动相关非常重要。解剖 MRI 扫描将包括 T1 加权、T2 加权、质子密度加权和 3D 梯度回忆采集。图像读取将在屏幕监视器上显示的图像上进行。 所有 MRI 图像均采用 DICOM 3 格式。 在德克萨斯大学圣安东尼奥分校的阅读课程中，控制总是以盲法的方式包含在内。可以使用男性控制装置。 Brey 博士和 Fox 博士（神经科医生和神经放射科医生）是主要读者。对于患者，我们记录精神疾病。对于定性分析，从大脑 MRI 扫描获得的图像将以盲法方式使用计算机投影显示在屏幕上。图像将以随机顺序投影，并由德克萨斯大学圣安东尼奥分校的神经学家一致阅读。 MRI 的评级为：0 = 正常，1 = 轻度萎缩，2 = 中度萎缩，任何局灶性病变，3 = 严重萎缩，> 5 个局灶性病变。研究人群：所有在霍普金斯大学进入的 Brain CONECTIONS 患者都有资格参加这项附加研究。结果测量：主要结果是评级量表 0、1（轻度）、2（中度）和 3（重度）。目前入组（2004 年 1 月 12 日 - 2005 年 11 月 30 日）：31 名患者已经完成了附加研究的第一次脑 MRI，其中 18 名患者还完成了 6 个月的随访 MRI。