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

描述（由申请人提供）：脑出血（ICH），从破裂的血管出血到大脑，仍然是最具破坏性的中风亚型，30天死亡率接近40%，大多数幸存者有严重的功能障碍。流出破裂血管的血量是ICH结局的最有力决定因素，虽然目前尚无经证实的急性ICH治疗方法，但观察到持续出血和血肿生长通常发生，这指向了一个诱人的治疗目标。两种干预措施（止血和抗高血压治疗）似乎可以减缓血肿的生长，但这种扩张的减少迄今未能在临床试验中转化为临床获益。这些观察结果强调了澄清血肿扩大与临床结局之间关系的重要性。 当前提案的动机是，改进的血肿生长的预测标志物和生物学表征将导致有效的、个性化的最佳治疗选择。这种方法的目标是将治疗靶向于扩展风险最高且最有可能对特定疗法作出反应的患者。我们重点关注两个神经影像学标志物，这两个标志物是我们小组和其他人的特征：1）对比CT血管造影术（CTA）上的对比剂汇集或“斑点征”，这是标准急诊头部CT的广泛使用的扩展; 2）在敏感的T2* 加权MRI序列上显示脑微出血（CMB），也是急性ICH常规诊断评估的一部分。越来越多的证据强烈支持CTA斑点征结果作为扩张可能性的有力预测因素。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物和血肿生长的相关风险。由于这两种方法检测ICH发病机制的不同方面，我们的期望是，他们将提供互补的生物学和预测信息的风险扩展。 我们的总体目标是应用CTA和MRI识别血肿扩大风险最高的患者。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是否可以识别血肿生长的高风险患者，以及这些成像技术是否可以选择更有可能从早期强化抗高血压治疗中获益的患者。 我们的建议利用了三个具体因素：1）在ATACH-2中收集的大量数据的基础上获得的巨大优势，2）三级卒中中心在ICH临床评价中广泛使用CTA和T2* 加权MRI（因此不需要单独的知情同意程序来入组我们的子研究），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。成功完成拟定研究将是优化当前和未来血肿生长方法应用和确定ICH结局明显改善的重要一步。

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.