Laser Speckle Imaging of Brain Tumor Vasculature

描述(申请人提供)：今年大约20,500名美国人将被诊断出患有中枢神经系统肿瘤。超过一半的确诊患者将失去生命。这些患者的主要治疗方法是手术切除加放射治疗。最近，非侵入性药物治疗已经发展到靶向抑制肿瘤血管生成。在这些治疗方案中对血管系统的评估是重要的，并辅之以成像方式。然而，超声的低分辨率和MRI成像的繁琐特性呈现出显著的局限性。此外，这些模式没有阐明肿瘤相关微血管的变化，这对于基于血管生成的研究工作是重要的。因此，脑癌研究和治疗干预将受益于成像技术的发展，以查看肿瘤部位的高分辨率、高对比度的血管图像。提出了一种新的基于激光散斑现象的成像方式。LS光学成像利用激光的随机反射特性来跟踪血管水平的血液流动。与其他现代成像方式不同，LS成像不需要使用造影剂，并且可以在极高的分辨率下使用。我们提出了一项第一阶段的工作，重点是为这种成像方式获得概念验证。具体地说，我们将开发一个配有图像处理套件的LS成像系统，以：1)增强肿瘤相关微血管的可视化，2)创建宽视野图像，以更好地显示暴露在脑中更广泛区域的血管。微血管将使用脊线跟踪算法增强，并将使用马赛克方法将单独的高分辨率图像拼接在一起，创建宽视野图像。在啮齿动物脑肿瘤模型中验证LS成像技术，通过使用平均血管密度的空间计算来量化肿瘤血管并与组织学结果相关联。第一阶段的主要里程碑是产生高分辨率和宽视野的肿瘤相关血管图像，并得到组织学证实。如果我们成功了，我们设想第二阶段的工作将集中在开发LS成像研究原型，以在动物模型中跟踪药物治疗和肿瘤血管生成。长期目标是建立一种临床LS成像设备，以提高脑癌患者手术治疗的可视化。公共卫生相关性：该项目的目标是开发一种新的基于激光散斑的成像模式，用于评估脑肿瘤血管生成。这项技术可用于测试新的肿瘤药物疗法，并最终在肿瘤切除过程中辅助手术中的血管成像。

DESCRIPTION (provided by applicant): Approximately 20,500 Americans will be diagnosed with a central nervous system tumor this year. Over half of those diagnosed will lose their lives. The mainstay of treatment for these patients has been surgical resection with radiation therapy. More recently, non-invasive pharmacotherapies have been developed to target inhibition of tumor angiogenesis. Evaluation of the vasculature during these treatment options is important and is aided by imaging modalities. However, the low resolution of ultrasound and cumbersome nature of MRI imaging present significant limitations. In addition, these modalities do not elucidate changes in tumor-associated microvasculature, which is important to investigate for angiogenesis-based research efforts. Thus, brain cancer research and therapeutic interventions would benefit from the development of imaging techniques to view high resolution, high contrast vascular images at the tumor site. We propose a new imaging modality based on the Laser Speckle (LS) phenomenon. LS optical imaging uses the random reflection nature of laser light to track the flow of blood at the vessel level. Unlike other modern imaging modalities, LS imaging does not require the use of a contrast agent and may be used at extremely high resolutions. We propose a Phase I effort focused on obtaining proof- of-concept for this imaging modality. Specifically, we will: " Develop an LS imaging system complete with an image processing suite to: 1) enhance the visualization of tumor-associated microvasculature, and 2) create wide field images to better visualize blood vessels across broader areas of the exposed brain. The microvasculature will be enhanced using a ridge tracking algorithm, and wide field images will be created by stitching together individual high-resolution images using a mosaicking method. " Validate the LS imaging technology in a rodent model of brain tumor by quantifying tumor vasculature using spatial calculations of Mean Vasculature Density and correlating with histological findings. The major milestone of Phase I is to produce high resolution and wide field images of tumor- associated vasculature with histological confirmation. If we are successful, we envision a Phase II effort focused on development of a LS imaging research prototype to track drug therapy and tumor angiogenesis in an animal model. The long-term goal is to build a clinical LS imaging device to improve visualization of surgical treatment in brain cancer patients. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a novel imaging modality based on laser speckle for evaluating brain tumor angiogenesis. This technology can be used to test new tumor drug therapies and eventually assist with intra-operative vasculature imaging during tumor resection.