Mechanisms of Brain Hemorrhage in Chronic Kidney Disease

慢性肾脏病脑出血的机制

基本信息

批准号：
10681454
负责人：
Peter Chang
金额：
$ 19.63万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10681454
关键词：
Academic Medical Centers Address Affect American Area Blood Blood Vessels Brain Brain hemorrhage Brain imaging California Cardiovascular system Cerebral hemisphere hemorrhage Chronic Kidney Failure County Databases Detection Disease Early Diagnosis Early identification Event Extravasation Functional disorder Hematoma Hemorrhage Hospitalization Image Incidence Individual Injury Institution Institutional Review Boards Investigation Kidney Kidney Diseases Medical center Modeling Neurological outcome Oranges Outcome Pathogenesis Pathway interactions Patients Persons Population Prevalence Prospective cohort Research Personnel Risk Risk Factors Scanning Severities Statistical Models Stroke United States Universities Vascular calcification X-Ray Computed Tomography brain magnetic resonance imaging calcification cerebral microbleeds cerebrovascular clinical database clinical investigation clinical risk cohort comorbidity deep learning diagnostic tool high risk imaging biomarker improved inhibitor inhibitor therapy innovation metropolitan mortality prospective randomized, clinical trials tool vascular injury

项目摘要

PROJECT SUMMARY Intracerebral hemorrhage (ICH) affects over two million people per year worldwide and is associated with a 54% one-year mortality. One important risk factor for ICH is chronic kidney disease (CKD), an entity that affects over 20 million people in the United States and is associated with higher ICH incidence and worse outcomes. ICH patients with advanced CKD have a 2.3-fold larger hematoma volume and a >4-fold increase in 1-year mortality. Given a prevalence as high as 14% in the U.S. population, CKD is a prime yet understudied disease in the pathogenesis of ICH. In this mechanistic clinical investigation, we hypothesize that CKD-induced vascular injury leading to ICH can be characterized by two intermediate imaging biomarkers: (1) intracranial arterial calcification (IAC), and (2) cerebral microbleeds (CMB). Specifically, we hypothesize that arteriolar injury in CKD results in higher IAC and CMB burden, which are predictive of ICH volume and hematoma expansion. To better characterize these relationships, this study leverages a 10-year institutional database of 1,500 spontaneous ICH patients spanning July 2011 and June 2020 as well as 150 prospective ICH patients aggregated over the first study year. For each patient, deep learning imaging analysis is used to quantify ICH volume as well as IAC burden on computed tomography scans. For patients with corresponding brain magnetic resonance imaging within 2-weeks of hospital admission, deep learning analysis will also be used to quantify CMB burden. Key target outcomes include prediction of ICH volume and hematoma expansion as a function of IAC and CMB burden stratified by CKD stage. In Specific Aim 1, the relationship between CKD status and IAC burden is characterized, which is used in combination with clinical risk factors to predict ICH volume and hematoma expansion. In Specific Aim 2, the relationship between CKD status and CMB burden is characterized, which is used in combination with IAC burden and clinical risk factors to predict ICH volume and hematoma expansion. All statistical models derived from the 10-year historic cohort of 1,500 patients are validated against the prospective cohort of 150 patients. Through an improved understanding of the shared pathophysiology between these disease states, quantitative models derived from the proposed analysis can be used for early identification of patients at high-risk for ICH and associated complications, who in turn are optimal candidates for aggressive management of underlying CKD.

项目概要脑出血 (ICH) 每年影响全球超过 200 万人，与 54% 的患者相关一年死亡率。 ICH 的一个重要危险因素是慢性肾脏病 (CKD)，这是一种影响超过美国有 2000 万人，与较高的 ICH 发生率和较差的结果相关。 ICH 晚期 CKD 患者的血肿量增加 2.3 倍，1 年死亡率增加 4 倍以上。鉴于 CKD 在美国人口中的患病率高达 14%，因此它是美国一种主要但尚未得到充分研究的疾病。 ICH的发病机制。在这项机制临床研究中，我们假设 CKD 引起的血管损伤导致 ICH 可能是以两种中间成像生物标志物为特征：（1）颅内动脉钙化（IAC）和（2）脑微出血（CMB）。具体来说，我们假设 CKD 中的小动脉损伤会导致较高的 IAC 和 CMB 负荷，可预测 ICH 体积和血肿扩张。为了更好地表征这些关系，本研究利用了 10 年机构数据库，其中包含 1,500 名自发性 ICH 患者，涵盖第一个研究年汇总了 2011 年 7 月和 2020 年 6 月以及 150 名前瞻性 ICH 患者。对于每个针对患者，深度学习成像分析用于量化 ICH 体积以及计算机的 IAC 负担断层扫描。对于入院2周内有相应脑磁共振检查的患者承认，深度学习分析也将用于量化CMB负担。主要目标成果包括根据 CKD 分层的 IAC 和 CMB 负荷预测 ICH 体积和血肿扩张阶段。在具体目标 1 中，描述了 CKD 状态与 IAC 负担之间的关系，使用结合临床危险因素来预测ICH体积和血肿扩张。在具体目标 2 中，表征 CKD 状态与 CMB 负担之间的关系，与 IAC 结合使用预测 ICH 体积和血肿扩张的负担和临床危险因素。所有统计模型的推导来自 1,500 名患者的 10 年历史队列中的结果与 150 名患者的前瞻性队列进行了验证。通过更好地了解这些疾病状态之间共同的病理生理学，定量从所提出的分析中得出的模型可用于早期识别 ICH 高风险患者以及相关的并发症，而这些人又是积极治疗潜在疾病的最佳候选者慢性肾病。