US-China Collaborative Research on Stroke Imaging

描述（由申请人提供）：约翰霍普金斯大学和北京医院的研究人员之间的这项合作研究项目的总体目标是验证一种新型的综合MRI检查方案，包括pH、弥散和灌注成像，用于评估缺血性卒中和卒中恢复。中风是全球成年人死亡和残疾的主要原因，在中国排名第二，在美国排名第四。目前，唯一FDA批准的缺血性卒中治疗是在症状发作后3小时内给予静脉内组织纤溶酶原激活剂（IV tPA）。中风发作后超过三小时的患者现在只在几个临床试验中接受治疗。然而，这种类型的治疗的选择标准仍然没有很好地定义。不幸的是，接受tPA的患者出血风险增加，这使情况进一步复杂化。因此，应根据缺血半暗带（定义为仍然存活但有梗死风险的组织）的存在和程度，在个体基础上评估tPA的获益与风险。APT成像是一种全新的MRI方法，可以无创地检测组织pH值。这种完全无创的pH成像方法可以识别有氧代谢受损后的组织酸中毒区域。我们假设，脑卒中中由于组织酸中毒引起的pH加权成像（pHWI）不足，可预测未开始再灌注时的最大最终梗死面积，在灌注/弥散MRI方案中增加APT-pH成像可更好地显示缺血半暗带，从而改善对最终梗死面积和结局的预测。我们将使用临床相关的大脑中动脉闭塞模型在动物身上测试我们的假设，并对超急性和急性缺血性中风患者进行试点人体扫描，以评估这种新技术在临床上的可能效用。我们的具体目标是：（i）评估大鼠脑缺血/再灌注模型中灌注/pH/弥散缺陷的特征和时空演变;和（ii）确定超急性和急性缺血性卒中患者的pH成像的放射学特征和临床价值。如果假设被证明是正确的，我们希望有一个额外的标记，可用于诊断和预后的中风患者在临床上。

DESCRIPTION (provided by applicant): The overall goal of this collaborative research project between researchers at Johns Hopkins University and Beijing Hospital is to validate a novel comprehensive MRI exam protocol, including pH, diffusion, and perfusion imaging, for the assessment of ischemic stroke and recovery from stroke. Stroke is a leading cause of death and disability among adults worldwide, second in China and fourth in the US. Currently, the only FDA- approved treatment for ischemic stroke is intravenous tissue plasminogen activator (IV tPA) that is given within three hours of symptom onset. Patients who present beyond three hours after stroke onset are now treated in several clinical trials only. However, the selection criteria for this type of therapy are still not well defined. This is further complicated by the unfortunate fact that patients who receive tPA are at increased risk for hemorrhage. Thus, the benefit versus risk with tPA should be assessed on an individual basis, based on the presence and extent of an ischemic penumbra, defined as tissue that is still viable but at risk of infarctio. APT imaging is an entirely new MRI methodology that can non-invasively detect tissue pH. This totally noninvasive pH imaging method can identify regions of tissue acidosis following impaired aerobic metabolism. We hypothesize that the pH-weighted imaging (pHWI) deficit in stroke, due to tissue acidosis, predicts the maximum final infarction size if no reperfusion is initiated, and he addition of APT-pH imaging to the perfusion/diffusion MRI protocol could better visualize an ischemic penumbra, thus improving predictions about final infarct size and outcome. We will test our hypothesis on animals, using a clinically relevant middle cerebral artery occlusion model, and perform pilot human scanning on hyperacute and acute ischemic stroke patients to assess the possible utility of this new technique in the clinic. Our specific aims are: (i) to assess the characteristics and spatio-temporal evolution of perfusion/pH/diffusion deficits in rat brain ischemia/reperfusion models; and (ii) to determine the radiologic characteristics and clinical values of pH imaging of hyperacute and acute ischemic stroke patients. If the hypotheses are proven correct, we expect to have an additional marker that can be used for diagnosis and prognosis of stroke patients in the clinic.