Development of kurtosis MRI to image acute stroke patients

开发峰度 MRI 来对急性中风患者进行成像

• 批准号: 8622820
• 负责人: Phillip Zhe Sun
• 金额: $ 21.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8622820
• 关键词: Acute; Adopted; Algorithms; Alteplase; American Heart Association; Angiography; Animals; Area; Biological; Brain; Characteristics; Classification; Clinic; Clinical; Clinical Research; Complex; Development; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Fibrinolytic Agents; Filament; Future; Heterogeneity; Histology; Hour; Human; Image; Imaging Techniques; Infarction; Injury; Ischemia; Ischemic Penumbra; Ischemic Stroke; Lesion; Magnetic Resonance Imaging; Maps; Methods; Modeling; Monitor; Outcome; Patients; Perfusion; Perfusion Weighted MRI; Pilot Projects; Play; Protocols documentation; Rattus; Recommendation; Reperfusion Therapy; Role; Stroke; Testing; Therapeutic; Time; Tissues; Translating; Translations; United States Food and Drug Administration; Variant; acute stroke; base; human subject; improved; indexing; injured; ischemic lesion; public health relevance; response; spatiotemporal; success; thrombolysis

Title: Development of kurtosis MRI to image acute stroke patients Project Summary/Abstract Early tPA thrombolysis is critical for ischemic stroke treatment, known as "time is brain". However, very few patients present for treatment within 3 hours of the stroke onset, the narrow therapeutic window of tPA. Because ischemic tissue injury is heterogeneous, imaging plays a crucial role in stroke patient management. Perfusion and diffusion (PWI and DWI) MRI have proven clinically useful as an imaging approximation to the ischemic tissue prior to infarction (penumbra). The rationale is that PWI identifies hypoperfused tissue while DWI defines the severely damaged ischemic core. As such, the PWI/DWI mismatch identifies the ischemic penumbra, and has been adopted in multiple trials to select patients for tPA therapy. Additionally, variant DWI- based paradigms, including MR angiogram (MRA)/DWI and clinical/DWI have been chosen to overcome the technical challenges of PWI to more practically guide tPA therapy in clinic. However, it is now recognized that the approximation of the DWI lesion as ischemic core is oversimplified. As noted in the recommendation for imaging of acute ischemic stroke from American Heart Association in both 2009 and 2013, "DWI is not a simple indicator of irreversible infarction but a complex variable that requires more study." Our proposal to develop kurtosis MRI as a means to augment the standard DWI is thus directly responsive to this call. We have recently established kurtosis MRI for imaging acute stroke. We demonstrated that kurtosis MRI detects the most severely damaged ischemic tissue within the conventional DWI lesion. Importantly, using a transient filament animal stroke model, we showed that kurtosis MRI defines the irreversibly damaged ischemic core while the DWI lesion without kurtosis abnormality recovers upon reperfusion. A key step before we can translate the new kurtosis MRI and guide tPA therapy in acute stroke patients is to evaluate it in an embolic stroke model that more reasonably mimics human stroke. Our central hypothesis is that kurtosis MRI is an ischemic core-specific index, which can overcome the limitation of conventional DWI for imaging acute stroke. Specifically, our proposal will use histology to verify that kurtosis MRI defines more severely injured ischemic tissue (Aim 1), determine kurtosis lesion response to tPA therapy in experimental stroke models (Aim 2), and translate and evaluate kurtosis MRI in the acute stroke clinical setting (Aim 3). The success of our proposal will establish the biological significance of kurtosis MRI, and establish DKI in the acute stroke clinical setting for future larger scale clinical studies.

标题：开发峰度MRI对急性卒中患者进行成像 项目总结/摘要 早期tPA溶栓对于缺血性卒中的治疗至关重要，被称为“时间就是大脑”。但很少 患者在中风发作的3小时内出现接受治疗，这是tPA的窄治疗窗。 由于缺血性组织损伤是异质性的，成像在卒中患者管理中起着至关重要的作用。 灌注和弥散（PWI和DWI）MRI已被证明在临床上可用作MRI的成像近似。 梗死前缺血组织（半暗带）。基本原理是PWI识别低灌注组织， DWI定义了严重受损的缺血核心。因此，PWI/DWI不匹配可识别缺血性 半暗带，并已在多项试验中采用，以选择患者进行tPA治疗。另外，DWI- 已选择基于范例，包括MR血管造影（MRA）/DWI和临床/DWI，以克服 PWI的技术挑战，以更实际地指导临床tPA治疗。然而，现在人们认识到， 将DWI病变近似为缺血核心过于简单化。如关于下列问题的建议所述， 美国心脏协会在2009年和2013年的急性缺血性卒中成像中，“DWI不是一个 不可逆转梗死的简单指标，但却是一个需要更多研究的复杂变量。“我们建议， 因此，开发峰度MRI作为增强标准DWI的手段直接响应了这一呼吁。 我们最近建立了峰度MRI成像急性中风。我们证明了峰度MRI 检测常规DWI病变中受损最严重的缺血组织。重要的是，使用 短暂的丝状动物中风模型，我们表明，峰度MRI定义了不可逆的缺血性损伤， 而无峰度异常的DWI病变在再灌注后恢复。关键的一步 翻译新的峰度MRI并指导tPA治疗急性脑卒中患者的目的是在栓塞性 更合理地模仿人类中风的中风模型。我们的中心假设是，峰度MRI是一个 缺血核心特异性指数，可克服常规DWI对急性脑卒中成像的局限性。 具体来说，我们的建议将使用组织学来验证峰度MRI定义更严重的缺血性损伤， 组织（目的1），确定实验性卒中模型中对tPA治疗的峰度病变反应（目的2），以及 翻译和评估峰度MRI在急性卒中临床环境中的作用（目的3）。我们的建议如果成功， 建立峰度MRI的生物学意义，并在急性卒中临床环境中建立DKI， 未来更大规模的临床研究。