EARLY DETERMINATION OF STROKE SUBTYPE: CT ANGIOGRAPHY

候选人是一名经过卒中奖学金培训的神经科医生，致力于急性卒中诊断和治疗。本申请提出了一个全面的计划，旨在发展成为一个独立的研究人员在以病人为导向的中风研究的候选人。 宾夕法尼亚大学拥有出色的临床、放射学和流行病学资源来支持这一提议。 该计划的培训部分包括临床流行病学和研究设计方面的正规研究生教育，特别侧重于血管疾病和技术评估。 研究部分是在卒中管理的背景下对新诊断工具进行前瞻性评价。该研究提案的中心假设是，中风机制的早期临床确定是有限的，但计算机断层扫描血管造影（CTA）将有效地识别具有特定中风机制的患者，以进行特定机制导向治疗。 缺血性卒中可能由几种不同病因之一引起，治疗可能最好针对潜在机制。 急性中风的治疗必须在中风发作后的最初几个小时内开始，但目前用于识别中风机制的方法在这一关键时期是不准确的。 用于确定卒中机制的金标准方法需要在治疗时间窗内无法获得的全面评估。 新的成像技术可能有助于早期确定卒中亚型，但尚未对其在卒中分诊和治疗中的效用进行正式分析。 一种非常有前途的新技术是CTA，这是一种快速的无创方法，可以使脑血管可视化。 具体目标：CTA在缺血性卒中亚型早期诊断中的作用将通过测量其阳性预测值（主要结局指标）、敏感性、特异性和可靠性来确定。 我们假设CTA的这些特征比目前的临床卒中诊断方法优越上级。 基于CTA的脑卒中机制诊断将与早期临床诊断相比较，最终将与金标准的最终诊断相比较。 将在卒中发作后24小时内对150例患者进行CTA检查。 研究者将根据现有临床信息对卒中机制进行早期评估，并对CTA结果设盲。 卒中机制将在诊断评估完成后最终确定。然后，研究者将使用临床和CTA数据来确定基于CTA的诊断。 将比较临床诊断和基于CTA的诊断的阳性预测值（PPV），针对多名评定者和多名患者进行调整。 该方法将首次正式评估CTA作为早期卒中诊断和选择具有特定卒中机制的患者进行特定机制导向卒中治疗的工具。

The candidate is a stroke fellowship-trained neurologist dedicated to a career in acute stroke diagnosis and treatment. This application proposes a comprehensive program designed to evolve the candidate into an independent investigator in patient- oriented stroke research. The University of Pennsylvania has outstanding clinical, radiological, and epidemiological resources to support this proposal. The training component of this plan entails formal graduate education in clinical epidemiology and research design, specifically focusing on vascular disease and technology assessment. The research component is a prospective evaluation of a new diagnostic tool in the context of stroke management. The central hypothesis of the research proposal is that early clinical determination of stroke mechanism is limited, but computed tomography angiography (CTA) will effectively identify patients with specific stroke mechanisms for specific mechanism- directed therapies. Ischemic stroke may be caused by one of several different etiologies, and treatment may be best directed toward the underlying mechanism. Therapy for acute stroke must be initiated in the first few hours after stroke onset, but current methods for identifying stroke mechanism are inaccurate during this critical time period. The gold standard method for determination of stroke mechanism requires a thorough evaluation that cannot be obtained within the therapeutic time window. New imaging techniques may be useful for the early determination of stroke subtype, but there has been no formal analysis of their utility in stroke triage and treatment. An extremely promising novel technique is CTA, a quick noninvasive method that allows for visualization of the cerebral vasculature. Specific Aims: The role of CTA in the early diagnosis of ischemic stroke subtype will be determined by measuring its positive predictive value (primary outcome measure), sensitivity, specificity, and reliability. We hypothesize that these characteristics are superior for CTA than current methods of clinical stroke diagnosis. CTA-based diagnosis of stroke mechanism will be compared with early clinical diagnosis, and ultimately will be compared with the gold standard final diagnosis. A cohort of 150 patients will be examined with CTA within 24 hours of the onset of stroke. Investigators will make an early assessment of stroke mechanism based on the available clinical information and will be blinded to CTA results. Stroke mechanism will ultimately be established after a diagnostic evaluation is completed. Investigators will then use both clinical and CTA data to determine a CTA-based diagnosis. The positive predictive value (PPV) of the clinical and CTA-based diagnoses will be compared, adjusting for multiple raters and multiple patients. This approach will, for the first time, formally evaluate CTA as a tool for early stroke diagnosis and selection of patients with specific stroke mechanisms for specific mechanism-directed stroke therapies.