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

目前的临床实践是不考虑潜在的性别差异来治疗中风。这是最好的方法吗？ 标准护理图像处理阈值被统一应用于所有患者，以识别潜在的 可挽救的与不可逆转的脑梗塞的脑组织。然而，女性经历缺血性中风的方式有所不同 而不是那些已知生理差异源自细胞水平的男性。因此，长期的研究 目标是在个性化成像的背景下表征男性和女性的急性缺血组织演变 急性再灌注治疗的患者选择和试验。 众所周知，治疗急性缺血性中风的益处随着发病时间的延长而下降。 治疗次数。延迟的患者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8小时内出现症状。缺血性卒中存在性别差异。女人 有更差的功能和患者报告的结果。尽管女性年龄较高，中风严重程度较高， 而中风时较差的健康状况在一定程度上解释了这些差异，但仍存在实质性的知识差距。 女性比男性更容易出现可治疗的缺血性中风。女性也有更好的功能 未经治疗的侧支网络和较慢的梗塞增长速度。为什么女性遭受更多的残疾如果她们是 呈现出良好的成像配置文件？这一矛盾是否源于所使用的成像定义的阈值 以确定梗死组织和潜在的可挽救组织？对于男性和女性来说，这些门槛会不会有所不同？ 最近的试验表明，成像阈值可用于识别对治疗有反应的患者。 如果缺血核心、可挽救半暗带和发病时间的最佳阈值对于男性和 女性，我们是不是因为没有纳入针对性别的治疗门槛而剥夺了患者的治疗好处？ 转化为治疗选择算法？ NINDS的使命是寻求关于大脑和神经系统的基础知识，并使用 为了减轻神经系统疾病的负担，该项目建议解决以下问题 知识差距并检验急性缺血组织进化在男性和女性之间存在差异的假设 女人。脑血流动力学的成像特征将直接与脑梗塞的演变相关，以评估性别 急性缺血性卒中患者急性再灌注治疗影像选择的差异 和审判。这将解决缺乏关于缺血性中风性别差异的研究，克服局限性 在临床试验的翻译相关性方面。拟议的项目将产生关于 性别对缺血组织演变的影响及对目前影像阈值选择的启示 用于识别梗死组织和潜在的可挽救组织。建立性别差异的证据 目的影像生物标志物是进一步完善患者个体化影像选择的一步。 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.