Acute Ischemic Tissue Evolution and Implications for Imaging Selection of Patients for Therapy and Clinical Trials using Sex-Disaggregated Data

急性缺血组织的演变以及对使用按性别分类数据进行治疗和临床试验的患者影像学选择的影响

• 批准号: 10818647
• 负责人: Adrienne Nicole Dula
• 金额: $ 6.02万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10818647
• 关键词: Acute; Address; Age; Algorithms; Anterior; Biological; Blood flow; Brain; Brain Infarction; Cell Survival; Clinical; Clinical Trials; Collateral Circulation; Data; Data Set; Diagnostic; Disease; Disparity; Drops; Eligibility Determination; Etiology; Evolution; Glucose; Goals; Growth; Health; Hour; Image; Infarction; Injury; Ischemia; Ischemic Stroke; Knowledge; Lesion; Linear Models; Measures; Mission; Modeling; National Institute of Neurological Disorders and Stroke; Nervous System; Outcome; Patient Outcomes Assessments; Patient Selection; Patients; Performance; Perfusion; Physiological; Reperfusion Therapy; Research; Scanning; Selection for Treatments; Severities; Sex Differences; Source; Stroke; Symptoms; Testing; Time; Tissues; Treatment Efficacy; Woman; Work; age effect; biological sex; brain tissue; cerebral hemodynamics; clinical practice; clinically relevant; cohort; disability; experience; follow-up; hypoperfusion; image processing; imaging biomarker; improved; male; men; nervous system disorder; optimal treatments; perfusion imaging; recruit; secondary analysis; sex; sex disparity; sexual dimorphism; standard of care; stem; stroke patient; stroke therapy; study population; treatment guidelines

Current clinical practice treats stroke without regard to potential sex differences. Is this the best approach? Standard of care image processing thresholds are uniformly applied across all patients to identify potentially salvageable versus irreversibly infarcted brain tissue. However, women experience ischemic stroke differently than men with known physiological differences originating at the cellular level. As such, the long-term research goal is to characterize acute ischemic tissue evolution for men and women in the context of personalized imaging selection of patients for acute reperfusion therapy and trials. It is well established that the benefit of treatment for acute ischemic stroke declines with longer onset to treatment times. Delayed patient presentation is the major treatment limitation with only one-third of all acute ischemic stroke patients presenting within 8 hours of symptoms. Sex disparities exist in ischemic stroke. Women have worse functional and patient-reported outcomes. Although women's higher age, greater stroke severity, and poorer health at the time of stroke partially explain these disparities, a substantial knowledge gap remains. Women present more often with treatable ischemic strokes than men. Women also have better-functioning collateral networks and slower infarct growth untreated. Why do women suffer from more disability if they are presenting with favorable imaging profiles? Does this paradox stem from the imaging-defined thresholds used to identify infarcted tissue and potentially salvageable tissue? Could these thresholds differ for men and women? Recent trials have demonstrated the utility of imaging thresholds to identify patients that will respond to treatment If the optimal thresholds for ischemic core, salvageable penumbra, and time from onset are different for men and women, are we denying patients the benefits of treatment by not incorporating sex-specific treatment thresholds into treatment selection algorithms? In line with NINDS's mission to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease, this project proposes to addresses these knowledge gaps and test the hypothesis that acute ischemic tissue evolution is different between men and women. Imaging features of cerebral hemodynamics will be directly related to infarct evolution to evaluate sex differences in acute ischemic stroke in the context of imaging selection of patients for acute reperfusion therapy and trials. This will address the paucity of studies on sex differences in ischemic stroke, overcoming limitations in translational relevance of clinical trials. The proposed project will result in generalizable evidence on the influence of sex on ischemic tissue evolution and inform on the selection of imaging-based thresholds currently used to identify infarcted tissue and potentially salvageable tissue. Establishing evidence of sex differences in objective imaging biomarkers is a step toward further refining the individualized imaging selection of patients for acute reperfusion therapy and trials.

目前的临床实践治疗中风时不考虑潜在的性别差异。这是最好的方法吗？ 护理标准图像处理阈值统一应用于所有患者，以识别潜在的 可挽救的梗塞脑组织与不可逆的梗塞脑组织。然而，女性经历缺血性中风的方式不同 与具有源自细胞水平的已知生理差异的男性相比。因此，长期研究 目标是在个性化成像的背景下描述男性和女性的急性缺血组织演变特征 选择患者进行急性再灌注治疗和试验。 众所周知，急性缺血性中风的治疗效果随着发病时间的延长而下降。 治疗次数。患者就诊延迟是主要的治疗限制，仅占所有急性患者的三分之一 缺血性中风患者在出现症状后 8 小时内出现症状。缺血性中风存在性别差异。女性 具有更差的功能和患者报告的结果。尽管女性年龄较大，中风严重程度较高， 中风时健康状况不佳部分解释了这些差异，但仍然存在巨大的知识差距。 女性比男性更容易出现可治疗的缺血性中风。女性也有更好的机能 未经治疗的侧支网络和梗塞生长缓慢。为什么女性会遭受更多的残疾？ 呈现良好的成像轮廓？这个悖论是否源于所使用的成像定义阈值 识别梗塞组织和可能可挽救的组织？男性和女性的这些阈值会有所不同吗？ 最近的试验证明了成像阈值可用于识别对治疗有反应的患者 如果男性和女性的缺血核心、可挽救半暗带和发病时间的最佳阈值不同 女性，我们是否因为不考虑性别特异性治疗阈值而剥夺了患者治疗的益处 进入治疗选择算法？ 根据 NINDS 的使命，寻求有关大脑和神经系统的基础知识并使用 该项目建议解决这些问题 知识差距并检验男性和女性之间急性缺血组织进化不同的假设 女性。脑血流动力学的影像学特征将与梗塞演变直接相关以评估性别 急性缺血性卒中在急性再灌注治疗患者影像学选择方面的差异 和考验。这将解决缺血性中风性别差异研究的缺乏问题，克服局限性 临床试验的转化相关性。拟议的项目将产生关于以下问题的普遍证据： 性别对缺血组织进化的影响以及目前基于成像的阈值选择的信息 用于识别梗塞组织和可能可挽救的组织。建立性别差异的证据 客观成像生物标志物是进一步完善患者个体化成像选择的一步 急性再灌注治疗和试验。