US-China Collaborative Research on Stroke Imaging

中美脑卒中影像学合作研究

• 批准号: 8545468
• 负责人: JINYUAN ZHOU
• 金额: $ 19.98万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545468
• 关键词: Acidosis; Acute; Adult; Alteplase; Amides; Animal Model; Animals; Area; Benign; Biological Markers; Blood Vessels; Blood flow; Brain Ischemia; Cause of Death; Cell Respiration; Cerebral Ischemia; Characteristics; China; Clinic; Clinical; Clinical Data; Clinical Trials; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Evolution; FDA approved; Geriatrics; Goals; Hemorrhage; Hospitals; Hour; Human; Image; Imaging Techniques; Imaging technology; Individual; Infarction; Intervention; Intravenous; Ischemia; Ischemic Penumbra; Ischemic Stroke; Lesion; Magnetic Resonance Imaging; Methodology; Methods; Middle Cerebral Artery Occlusion; Modeling; Morbidity - disease rate; Outcome; Patients; Perfusion; Protocols documentation; Protons; Rattus; Reperfusion Therapy; Research; Research Personnel; Research Project Grants; Research Proposals; Risk; Scanning; Selection Criteria; Sensitivity and Specificity; Staging; Stroke; Surrogate Markers; Symptoms; Techniques; Testing; Therapeutic; Time; Tissues; Universities; Weight; acute stroke; base; brain tissue; clinical application; clinically relevant; design; disability; imaging modality; improved; mortality; novel; outcome forecast; public health relevance; restoration; spatial relationship; stroke recovery

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.

描述（由申请人提供）：约翰·霍普金斯大学和北京医院研究人员之间的这一合作研究项目的总体目标是验证一种新颖的综合 MRI 检查方案，包括 pH、扩散和灌注成像，用于评估缺血性中风和中风恢复。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，FDA 批准的唯一治疗缺血性中风的方法是静脉注射组织纤溶酶原激活剂 (IV tPA)，在症状出现后三小时内给予。目前仅在几项临床试验中对中风发作后超过三小时就诊的患者进行治疗。然而，此类治疗的选择标准尚未明确。不幸的是，接受 tPA 的患者出血风险增加，这一事实使情况变得更加复杂。因此，tPA 的获益与风险应根据缺血半暗带的存在和程度进行个体评估，缺血半暗带定义为仍然存活但有梗塞风险的组织。 APT 成像是一种全新的 MRI 方法，可以非侵入性地检测组织 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，由于组织酸中毒，中风中的 pH 加权成像 (pHWI) 缺陷可以预测如果不开始再灌注，最终的最大梗塞面积，并且将 APT-pH 成像添加到灌注/扩散 MRI 方案中可以更好地可视化缺血半暗带，从而改善对最终梗塞面积和结果的预测。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，以评估这项新技术在临床中的可能效用。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/扩散缺陷的特征和时空演变； (ii) 确定超急性和急性缺血性中风患者的放射学特征和 pH 成像的临床价值。如果这些假设被证明是正确的，我们期望有一个额外的标记物可以用于临床中中风患者的诊断和预后。