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

目前的临床实践在治疗中风时没有考虑潜在的性别差异。这是最好的方法吗？ 标准护理图像处理阈值统一应用于所有患者，以识别潜在的 可挽救的脑组织和不可逆的脑梗死组织。然而，女性缺血性中风的经历不同， 比那些在细胞水平上有生理差异的男性更容易被发现。因此，长期研究 目的是在个性化成像的背景下描述男性和女性急性缺血组织演变的特征 急性再灌注治疗和试验的患者选择。 已经确定，急性缺血性卒中的治疗获益随着发病时间的延长而下降， 治疗时间。延迟的病人表现是主要的治疗限制，只有三分之一的急性 缺血性中风患者在出现症状8小时内。缺血性卒中存在性别差异。妇女 有更差的功能和患者报告的结果。尽管女性年龄越大，中风越严重， 和中风时的健康状况较差部分解释了这些差异，但仍然存在大量的知识差距。 女性比男性更常出现可治疗的缺血性中风。女性也有更好的功能 侧支网络和较慢的梗死生长未经处理。为什么妇女遭受更多的残疾，如果他们是 呈现出良好的影像学特征这种矛盾是否源于所使用的成像定义阈值 来识别梗死组织和潜在的可挽救组织这些门槛对男性和女性是否有所不同？ 最近的试验表明，成像阈值的效用，以确定患者将响应治疗 如果男性和女性的缺血核心、可挽救的半暗带和发病时间的最佳阈值不同， 女性，我们是否通过不纳入性别特异性治疗阈值来剥夺患者的治疗益处 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 该知识，以减少神经系统疾病的负担，该项目提出，以解决这些 知识差距和测试假设，急性缺血组织演变是不同的男性和 妇女脑血流动力学的影像学特征将直接关系到梗死演变的性别来评价 急性缺血性卒中患者急性再灌注治疗影像学选择的差异 和审判这将解决缺血性卒中性别差异研究的不足，克服局限性 临床试验的翻译相关性。拟议的项目将产生关于下列问题的可推广的证据： 性别对缺血性组织演变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潜在的可挽救组织。建立性别差异的证据 客观的成像生物标志物是进一步完善患者的个性化成像选择的一步， 急性再灌注治疗和试验。

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.