One Stop Shop Imaging for Acute Ischemic StrokeTreatment

 描述(申请人提供)：中风是美国导致死亡和残疾的主要原因之一。在美国，每年有超过79.5万人中风；超过10万人将死亡，其他大多数人将遭受不同程度的神经损伤。美国国立卫生研究院的一项估计表明，每年照顾中风患者的费用超过730亿美元的美国医疗保健美元。虽然在中风患者的护理方面取得了许多进展(例如，预防措施和康复)，但一旦中风发生，有效预防或限制神经损伤的能力仍然难以捉摸。只有一小部分急性中风患者适合接受血管内治疗；据估计，这个数字每年在58,000到120,000之间。影响成功血管重建的可能性，更重要的是影响良好临床结果的关键因素是：1)从中风发病到血管重建的时间，以及2)区分脑体积小但不可逆性损伤的脑(缺血核心)和大量缺血但可挽救的脑(半暗带)与存在大的缺血核心且极少或没有半暗带的患者的能力。正是基于这两个因素，我们相信所提出的技术的应用将产生量子影响。我们的首要目标是利用现有的C臂锥束CT数据采集系统开发一种新的成像工作流程，这些系统目前在全球血管造影套件中广泛使用。我们相信，这一新的临床模式将使选定的急性缺血性中风(AIS)患者能够使用单一方式进行诊断、分类和治疗，从而大大减少从中风发病到治疗的时间延迟。拟议的成像方案提供的成像数据将增强选择最有可能从血运重建中受益的患者的能力，并消除那些血运重建可能无效或可能有害的患者。这一新的工作流程是由一种革命性的图像重建技术实现的，即由该项目的PI发明的同步多伪影减少与断层重建(SMART-Recon)技术。这种新的重建方法从根本上挑战了教科书和其他最新文献中所写的图像重建的传统条件：它的应用使得能够使用从一系列角度段获取的数据来重建时间分辨的CT图像，所述角度段的角度跨度约为60度，而不是传统的180度加扇角的标准。这项新技术实现了基于C臂的锥束CT成像的巨大飞跃，使人们能够在超低辐射剂量水平下获取和重建高时间分辨率的图像。这些SMART-Recon处理后的图像可用于生成非增强CT图像以排除出血的存在，时间分辨锥束CT血管成像以评估闭塞和侧支循环的位置，以及CT灌注参数图像以评估缺血核心和半暗带的范围，从而满足血管成像套件中一站式成像的成像要求。更有价值的是，能够在辐射暴露水平如此低的情况下获得这些图像，以至于在干预期间进行多项评估变得可行。因此，在这个建议中，主题是用这种技术上的创新来实现临床实践的量子飞跃。为了充分优化和验证所提出的急性缺血性中风诊断和治疗的成像工作流程，使用动物模型和人类受试者研究计划了三个目标。目标#1的目的是开发和优化SMART-Recon技术，以实现一站式成像；目标#2是在动物研究中验证一站式工作流程；目标#3是在两阶段的人体受试者研究中验证一站式成像。在完成提出的目标和相关的可量化里程碑之后，应该已经开发了一个新的神经血管成像平台，并在临床环境中进行了测试。它将为AIS患者的诊断、患者选择、治疗计划、治疗交付和治疗效果评估提供图像指导。在AIS患者中，“时间就是大脑”的程度怎么夸大都不为过。因此，与拟议的革命性成像技术实现的当前技术相比，可以节省时间的工作流程应该允许在诊断和治疗急性缺血性中风患者方面实现质的飞跃。

 DESCRIPTION (provided by applicant): Stroke is one of the leading causes of death and disability in the United States. Each year more than 795,000 people in the U.S. have a stroke; over 100,000 will die and a majority of the others will suffer varying degrees of neurological injury. An NIH estimate indicated that the cost of caring for people with strokes exceeded $73 billion in U.S. healthcare dollars each year. While many advances have been made in the care of people with strokes (e.g. preventative measures and rehabilitation), once a stroke has occurred, the ability to effectively prevent or limit neurological injury remains elusive. Only a small fraction of people having an acute stroke are suitable candidates for endovascular therapy; estimates place this number between 58,000 and 120,000 per year. Critical factors which impact both the likelihood of successful revascularization and, more importantly, the chances of a good clinical outcome are: 1) the time from onset of a stroke to revascularization and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from ones where there is a large ischemic core and very little or no penumbra. It is on these two factors that we believe the application of the proposed techniques will have a quantum impact. Our overarching objective is to develop a new imaging workflow using available C-arm cone-beam CT data acquisition systems that are currently widely available in angiography suites worldwide. We believe that this new clinical paradigm will enable selected patients with an acute ischemic stroke (AIS) to be diagnosed, triaged, and treated using a single modality, thus greatly reducing delay in the time from stroke onset to treatment. The proposed imaging scheme provides imaging data that will enhance the ability to select those patients most likely to benefit from revascularization and eliminate ones for whom revascularization may be futile or potentially harmful. This new workflow is enabled by a revolutionary image reconstruction technique, namely the Synchronized Multi-Artifact Reduction with Tomographic RECONstruction (SMART-RECON) technique, invented by the PI of the project. This new reconstruction method fundamentally challenges the traditional conditions for image reconstruction written in textbooks and other recent literature: Its application enables the reconstruction of time-resolved CT images using data acquired from a series of angular segments taken over an angular span of about 60 degrees rather than the conventional standard of 180 degrees plus the fan angle. This new technique enables a quantum leap in C-arm based cone beam CT imaging, allowing one to acquire and reconstruct high temporal resolution images at ultra low radiation dose levels. These SMART- RECON processed images may then be used to generate non-contrast CT images to exclude the presence of hemorrhage, time-resolved cone beam CT angiography to evaluate the site of occlusion and collaterals, and CT perfusion parametric images to assess the extent of ischemic core and penumbra, thereby fulfilling the imaging requirements for one-stop-shop imaging in an angiography suite. Adding further value is the ability to obtain these images with such low levels of radiation exposure that multiple assessments during an intervention become feasible. Therefore, in this proposal, the theme is to use this innovation in technology to take a quantum leap forward in clinical practice. To fully optimize and validate the proposed imaging workflow for acute ischemic stroke diagnosis and treatment, three aims are planned using both an animal model and human subject studies. The purpose of Aim #1 is to develop and optimize the SMART-RECON technique to enable One-Stop-Shop imaging; Aim #2 is to validate One-Stop-Shop workflow in animal studies; and Aim #3 is to validate One-Stop-Shop imaging in a two-phase human subject studies. Upon the completion of the proposed aims and the associated quantifiable milestones, a new neurovascular imaging platform should have been developed and tested in clinical environment. It will provide image guidance for diagnosis, patient selection, treatment planning, treatment delivery, and treatment efficacy assessment in patients presenting with an AIS. It is impossible to overstate the degree to which "Time is Brain" in patients with an AIS. Thus, a workflow which can save time compared to current techniques enabled by the proposed revolutionary imaging technology should allow for a quantum leap in diagnosis and treatment for patients suffering from an acute ischemic stroke.