ERIS - Effective Reserve In Stroke

ERIS - 有效储备冲程

• 批准号: 10724761
• 负责人: Markus D Schirmer
• 金额: $ 45.42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724761
• 关键词: Accident and Emergency department; Accounting; Acute; Admission activity; Age; Aging; Area; Biological; Biological Markers; Blood Vessels; Brain; Cerebrovascular Disorders; Characteristics; Clinical; Cognitive; Compensation; Data; Dementia; Dimensions; Disease; Drops; Ensure; Event; Goals; Image; Investigation; Ischemic Stroke; Lesion; Machine Learning; Measures; Methodology; Modeling; Nature; Neurodegenerative Disorders; Outcome; Pathologic; Pathology; Patient-Focused Outcomes; Patients; Pattern; Persons; Phenotype; Population; Prevalence; Resolution; Site; Stroke; Techniques; Testing; Time; Validation; Variant; White Matter Hyperintensity; acute stroke; age related; brain health; brain volume; burden of illness; cerebrovascular pathology; clinical imaging; clinically relevant; clinically significant; cognitive reserve; cohort; deep learning; design; disability; efficacy validation; functional disability; functional independence; functional outcomes; high dimensionality; image processing; imaging biomarker; imaging study; improved outcome; insight; mixed dementia; multidisciplinary; neuroimaging; neuroimaging marker; personalized care; post stroke; prevent; prognostication; quantitative imaging; segmentation algorithm; specific biomarkers; stroke model; stroke outcome; stroke patient; stroke risk; targeted treatment; translational approach; translational potential; treatment optimization

PROJECT SUMMARY/ABSTRACT Stroke and dementia are two of the leading contributors to age-related disease burden and long-term disability. With aging populations in the US and worldwide, the prevalence of stroke increases and it becomes imperative to prevent related long-term functional disability from cerebrovascular disease and pathology. Understanding the determinants of post-stroke outcome that may lead to functional independence is of great clinical significance and essential to developing targeted treatment options. In the field of neurodegenerative diseases, the concepts of structural and functional reserve have been invoked to explain better than expected cognitive outcomes. Reserve describes the brain’s capacity to compensate for pathology. Specifically in stroke, elucidating such protective mechanisms has major practical implications for understanding outcome, however, few studies have investigated these concepts in stroke populations. Structural reserve generally aims to quantify the maximum brain reserve of a person, while pre-existing disease burden is not accounted for. The remaining, effective reserve, however, more likely reflects the brain’s ability to compensate for a sudden vascular event. The overall goal of this project is to create a translational approach to estimate the effective reserve from the low-resolution clinical imaging data of patients with acute ischemic stroke as they are acquired in the emergency department, and expand the concept by incorporating longitudinal and spatial lesion information to help improve outcome modeling. Aim 1 will investigate the concept of effective reserve and its feasibility in patients with acute ischemic stroke. We leverage two large-scale, retrospective stroke cohorts with clinical imaging available (single site: N=453, multi-site: N=912). To ensure the translational nature of effective reserve, we will enhance existing and develop new deep-learning enabled image processing pipelines to extract the required quantitative imaging biomarkers. These biomarkers will then be used to model functional outcome, measured as modified Rankin Scale score, ~90 days post-stroke. Aim 2 will develop longitudinal assessment methodologies for effective reserve and investigate how a drop in effective reserve post-stroke impacts stroke outcome. Aim 3 will further enhance this principle by harnessing spatial information of the stroke lesion and determining its impact on the brain’s ability to compensate for pathology. An important and unique feature of this project lies in its direct translational potential, as it is assessed on stroke neuroimaging data acquired in the emergency department to answer important questions about the brain’s ability to compensate for the acute vascular event and its focus on protective mechanisms in the brain relating to brain health. To achieve these goals, this project leverages unique data and multidisciplinary expertise, to create a clinically available, longitudinal, and spatially specific biomarker that enhances real-time stroke prognostication, and which can guide individualized patient care to improve outcomes.

项目概要/摘要 中风和痴呆是与年龄相关的疾病负担和长期残疾的两个主要原因。 随着美国和世界范围内的人口老龄化，中风的患病率不断增加，这已成为当务之急 预防脑血管疾病和病理导致的相关长期功能障碍。了解 可能导致功能独立的卒中后结果的决定因素具有重要的临床意义 对于制定有针对性的治疗方案至关重要。在神经退行性疾病领域，概念 结构和功能储备的增加被用来解释比预期更好的认知结果。 储备描述了大脑补偿病理的能力。特别是在中风方面，阐明了这样的 保护机制对于理解结果具有重大的实际意义，然而，很少有研究表明 研究了中风人群中的这些概念。结构储备通常旨在量化最大 一个人的大脑储备，而不考虑预先存在的疾病负担。剩余有效 然而，储备更可能反映了大脑补偿突发血管事件的能力。整体 该项目的目标是创建一种转化方法来估计低分辨率的有效储量 在急诊科获得的急性缺血性中风患者的临床影像数据， 并通过整合纵向和空间病变信息来扩展概念，以帮助改善结果 造型。目标 1 将研究有效储备的概念及其在急性缺血患者中的可行性 中风。我们利用两个具有可用临床影像的大规模回顾性卒中队列（单中心： N=453，多站点：N=912）。为确保有效储备的转化性，我们将加强现有和 开发新的深度学习图像处理管道来提取所需的定量图像 生物标志物。然后，这些生物标志物将用于模拟功能结果，并以改良 Rankin 进行测量 中风后约 90 天的量表评分。目标 2 将开发纵向评估方法，以实现有效的 储备并研究中风后有效储备的下降如何影响中风结果。目标3将进一步 通过利用中风病变的空间信息并确定其对 大脑补偿病理的能力。该项目的一个重要且独特的特点在于它的直接 转化潜力，因为它是根据急诊科获得的中风神经影像数据进行评估的 回答有关大脑补偿急性血管事件的能力及其重点的重要问题 与大脑健康相关的大脑保护机制。为了实现这些目标，该项目利用了独特的 数据和多学科专业知识，创建临床可用的、纵向的、空间特异性的生物标志物 增强实时中风预测，并可以指导个体化患者护理以改善 结果。