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BBB Permeability Imaging in CADASIL

BBB Permeability Imaging in CADASIL
CADASIL 中的 BBB 渗透性成像
批准号:
10335122
负责人:
Danny JJ WANG
金额:
$24.75万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-02-01 至 2025-01-31

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中文摘要
翻译
项目摘要/摘要 这个美国-中国生物医学研究合作项目的目的是了解 血脑屏障在脑小血管病发病机制中的作用及验证 通透性成像作为SVD的早期标志物。SVD是中风、脑白质(WM)疾病的主要原因 和痴呆症,但大脑损伤和认知能力下降的机制在很大程度上仍然难以捉摸。这 该提案将检验这样的假设,即血脑屏障的破坏在人类中引发疾病的发生和发展 常染色体显性遗传性脑动脉病的基因定义SVD(NOTCH3突变携带者) 伴有皮质下梗塞和白质脑病(CADASIL)。该提案将使用一组独特的 中国CADASIL患者已在首都医科大学宣武医院排队接受研究 在北京。采用3特斯拉和7特斯拉的尖端BBB渗透率成像技术,使用动态对比度 增强(DCE)MRI和扩散加权动脉自旋标记(DW ASL),以及其他创新 SVD的生物标记物作为MarkVCID财团(www.markvsid.org)的一部分,我们将系统地调查 CADASIL进展过程中的临床、神经心理和影像变化。在三个目标中,我们将首先 Gd基造影剂血脑屏障通透性的可重复性及相关性评价 (GBCA)和水分别在中国CADASIL患者队列中。通过纵向研究,我们将 然后用DCE MRI和DW ASL确定中国人队列中血脑屏障破坏的启动作用 CADASIL患者验证NOTCH3突变携带者血脑屏障通透性增加的假设 引发疾病的发生和发展,如脑血流量(CBF)减少、WM的发展 损伤和自由水含量,缺血性脑梗塞和微出血,以及认知能力下降。我们将进一步 CADASIL患者包括血脑屏障通透性的多参数磁共振成像方案的建立和评估 7T超高场成像。利用中国CADASIL患者的独特队列,并应用 尖端成像方法在3T和7T,这个美国和中国的生物医学合作项目将定义 血脑屏障功能障碍在脑SVD中的启动作用,并将建立血脑屏障作为治疗的新的关键靶点 CADASIL和SVD的治疗干预。该项目还将产生尖端的BBB 3T和7T透气性成像方案可作为SVD的早期成像标志。
英文摘要
Project Summary/Abstract The purpose of this US-China Biomedical Research Collaboration project is to understand the role of the blood-brain barrier (BBB) in the pathogenesis of cerebral small vessel disease (SVD) and to validate BBB permeability imaging as an early marker of SVD. SVD is a major cause of stroke, white matter (WM) disease and dementia, but the mechanisms underlying brain damage and cognitive decline remain largely elusive. This proposal will test the hypothesis that BBB breakdown initiates disease onset and progression in humans with genetically defined SVD (NOTCH3 mutation carriers suffering from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL). The proposal will use a unique cohort of Chinese CADASIL patients already lined up for study inclusion at Xuanwu Hospital, Capital Medical University in Beijing. With cutting-edge BBB permeability imaging techniques at 3 and 7 Tesla, using dynamic contrast enhanced (DCE) MRI and diffusion-weighted arterial spin labeling (DW ASL), as well as other innovative biomarkers of SVD as part of the MarkVCID consortium (www.markvcid.org), we will systematically investigate the clinical, neuropsychological, and imaging changes during CADASIL progression. In 3 aims, we will first evaluate the repeatability and correlation between BBB permeability to Gadolinium-based contrast agent (GBCA) and water respectively in the cohort of Chinese CADASIL patients. Using a longitudinal study, we will then determine the initiating role of BBB breakdown using DCE MRI and DW ASL in the cohort of Chinese CADASIL patients to test the hypothesis that increased BBB permeability in NOTCH3 mutation carriers initiates disease onset and progression, such as cerebral blood flow (CBF) reductions, development of WM lesions and free water content, ischemic infracts and mircrohemorhages, and cognitive decline. We will further develop and evaluate a multiparametric MRI protocol for CADASIL patients including BBB permeability imaging at ultrahigh field of 7T. Leveraging a unique cohort of Chinese CADASIL patients, and applying cutting-edge imaging approaches at 3 and 7T, this US-China Biomedical Collaboration project will define the initiating role of BBB dysfunction in cerebral SVD, and will establish the BBB as a new key target for therapeutic interventions in CADASIL and by extension SVD. This project will also result in cutting-edge BBB permeability imaging protocols at 3 and 7T as early imaging markers of SVD.
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