SCORE-IT: The CTA Spot Sign Score in Acute Cerebral Hemorrhage

描述(申请人提供)：脑出血(ICH)，从破裂的血管出血进入大脑，仍然是最具破坏性的中风亚型，30天死亡率接近40%，大多数幸存者出现严重的功能障碍。从破裂的血管流出的血量是脑出血预后的最强有力的决定因素，虽然目前还没有证实的治疗急性脑出血的方法，但观察到持续出血和血肿增长通常指向一个诱人的治疗目标。有两种干预措施(止血和降压治疗)似乎减缓了血肿的增长，但到目前为止，这种减少的扩张在临床试验中并未转化为临床益处。这些观察结果强调了澄清血肿扩大和临床结果之间关系的重要性。目前这项提议的动机是，改进的血肿增长预测标志物和生物学特征将导致高效、个性化的最佳治疗选择。这种方法的目标是针对扩展风险最高、对特定治疗最有可能有效的患者进行治疗。我们关注两个神经影像标志物：1)对比CT血管造影(CTA)上的对比度或“斑点征”，这是标准头颅急诊CT的广泛应用延伸；2)在敏感的T2加权MRI序列上显示脑微出血(CMB)，这也是急性脑出血常规诊断评估的一部分。越来越多的证据有力地支持了CTA斑点征的发现，认为它是扩张可能性的有力预测指标。来自MRI成像的数据，虽然不太确定，但也暗示CMB是微血管结构的标志和血肿生长的相关风险。由于这两种方法检测脑出血发病机制的不同方面，我们期望它们将提供关于扩张风险的互补的生物学和预测性信息。我们的总体目标是应用CTA和MRI来确定血肿扩大的最高风险患者。与急性脑出血抗高血压治疗-2(ATACH-2)试验合作，我们将确定CTA和MRI是否可以识别血肿增长的高风险患者，以及这些成像技术是否可以选择更有可能从早期强化降压治疗中受益的患者。我们的建议利用了三个具体因素：1)在ATACH-2收集的丰富数据的基础上获得的巨大影响力，2)三级卒中中心在脑出血的临床评估中广泛使用CTA和T2*加权MRI(因此不需要单独的同意程序即可参加我们的子研究)，以及3)我们的研究小组在解释这两种技术方面的广泛认可的专业知识。拟议研究的成功完成将是朝着优化当前和未来血肿生长方法的应用并确定脑出血预后的切实改善迈出的重要一步。

DESCRIPTION (provided by applicant): Intracerebral hemorrhage (ICH), bleeding into the brain from a ruptured blood vessel, remains the most devastating stroke subtype, with 30-day mortality approaching 40% and severe functional impairments in the majority of survivors. The amount of blood that exits the ruptured vessel is the most powerful determinant of outcome in ICH, and while there are currently no proven treatments for acute ICH, the observation that continued bleeding and hematoma growth commonly occur points to an inviting therapeutic target. Two interventions (hemostatic and antihypertensive therapy) appear to slow hematoma growth, but this reduced expansion has thus far failed to translate into clinical benefit in clinical trials. These observations underscore the importance of clarifying the relationship between hematoma expansion and clinical outcome. Motivating the current proposal is the idea that improved predictive markers and biological characterization of hematoma growth will lead to efficient, personalized selection of optimal therapy. The goal of this approach is to target treatment to patients at highest risk for expansion and likeliest to respond to a specific therapy. We focus on two neuroimaging markers characterized by our group and others: 1) pooling of contrast or "spot sign" on contrast CT angiography (CTA), a widely used extension of the standard emergency head CT; and 2) demonstration of cerebral microbleeds (CMB) on sensitive T2*-weighted MRI sequences, also part of the routine diagnostic evaluation of acute ICH. Accumulating evidence strongly supports CTA spot sign findings as powerful predictors of likelihood of expansion. Data from MRI imaging, though less definitive, also implicate CMB as markers of microvascular structure and associated risk of hematoma growth. As these two methods detect distinct aspects of ICH pathogenesis, our expectation is that they will provide complementary biological and predictive information regarding risk of expansion. Our overall goal is to apply CTA and MRI to identify patients at highest risk for hematoma expansion. Partnering with the Antihypertensive Treatment in Acute Cerebral Hemorrhage-2 (ATACH-2) trial, we will determine whether CTA and MRI can identify patients at high risk for hematoma growth and whether these imaging techniques can select patients more likely to benefit from early, intensive antihypertensive treatment. Our proposal takes advantage of three specific factors: 1) the tremendous leverage obtained from building on the wealth of data to be collected in ATACH-2, 2) the widespread use of CTA and T2*-weighted MRI by tertiary stroke centers in the clinical evaluation of ICH (thus necessitating no separate consent process for enrollment in our substudy), and 3) our research group's widely recognized expertise in the interpretation of both of these techniques. Successful completion of the proposed studies will be a major step towards optimizing the application of current and future approaches to hematoma growth and establishing tangible improvements in ICH outcome.