Dynamic micro-CT using a field emission x-ray source

描述（由申请人提供）： 本提案的目的是开发一种动态微计算机断层扫描（micro-CT）系统，与目前的商业micro-CT扫描仪相比，具有增强的空间和时间分辨率和更通用的成像能力，并探索其在生物医学研究中的应用。目标是提供一种扫描仪，其将最大化图像分辨率用于小鼠的体内扫描，并且目标器官系统是心肺系统。建议的系统将利用微焦点场发射X射线源最近在我们的实验室证明。与传统的微焦点X射线源相比，碳纳米管（CNT）为基础的场发射X射线源提供了高分辨率，大大减少了尺寸，快速脉动能力目前还不可能，以及更高的通量的潜力。所提出的CT扫描仪具有门控场发射X射线源、数字2D X射线探测器和电动物体载物台，可以同步X射线曝光、数据收集、物体旋转和物体的生理信号。该系统将能够以每幅图像1-10毫秒的速率进行触发和门控成像，并将具有30克或更低的分辨率，这些能力在目前的门控微型CT系统中尚未得到证实，将为生物医学研究提供新的成像模式，如小动物的动态心脏和肺成像。当完全实现时，可以在10分钟内获得心脏运动的完整周期的动态CT图像。新的设计还将大大降低微型CT扫描仪的成本和物理尺寸，从而使该技术更容易为研究界所用。 已经获得了大量的初步结果，它们证实了我们的假设的有效性。我们还在纳米技术方面建立了广泛的基础设施，这将用于这项拟议的研究。我们预计这项研究将有很高的成功概率。 在R21阶段（第一年），我们将设计，建造和评估一个使用碳纳米管作为电子源的三极管型场发射X射线源。X射线源的目标特性为：100-500？管电流30？分辨率40- 100 KVp，脉冲宽度和重复频率可编程（在高达10 KHz时宽度小于0.1毫秒），通量波动小于1%。我们将进一步设计并制作一个具有电子选择性可变焦斑尺寸的场发射X射线源。将对X射线管的成像能力和性能特征进行评估，并与商业微焦点X射线源进行比较。 在R33阶段（第2-4年），我们将使用场发射X射线源、商用高分辨率快速响应数字二维X射线探测器和锥束重建算法组装动态微型CT扫描仪。将开发用户界面、仪器控制和成像软件。通过电子同步X射线曝光、数据收集、对象运动和生理信号，该系统将实现具有高空间和时间分辨率的动态CT成像。校准后，我们将展示1）高分辨率成像？ENaC转基因小鼠气道粘液量与存活率的关系; 2）心肺运动动态显像。 我们已经组建了一个由材料科学、医学物理、放射学和生理学领域的顶尖科学家和工程师组成的团队，他们来自美国加州大学（Zhou，Lu，Grubb，Lin和Boucher）、美国国家科学院（NCSU）（Lalush）和爱荷华州大学（U of Iowa）（霍夫曼，麦克伦南）。这项研究将主要在北卡罗来纳州纳米材料中心进行，该中心是PI的创始主任。Zhou和Lu在CNT场发射技术方面拥有丰富的经验，并且是第一批使用CNT演示冷阴极X射线管的人。他们将主要负责仪器的开发。Lalush将负责图像重建工作。霍夫曼和麦克伦南是在动态，容积心肺CT成像和图像分析领域的领先专家。他们将建议CT设计，将其性能与商业系统进行比较，并在测试应用中使用该系统进行动态成像：吸烟小鼠肺气肿模型。Grubb、Lin和Boucher将利用CT扫描仪来评估气道病理。

DESCRIPTION (provided by applicant): The aim of this proposal is to develop a dynamic micro-computed tomography (micro-CT) system with enhanced spatial and temporal resolution and more versatile imaging capabilities compared to the current commercial micro-CT scanners, and to explore its applications for biomedical research. The goal is to provide a scanner that will maximize image resolution for in vivo scanning of mice and with the target organ systems being the cardiopulmonary system. The proposed system will utilize a micro-focus field-emission x-ray source recently demonstrated in our laboratory. Compared to the conventional micro-focus x-ray sources with thermionic cathodes, the new carbon nanotube (CNT) based field emission x-ray source offers high resolution at significantly reduced size, fast pulsation capability currently not possible, and the potential for higher flux. The proposed CT scanner with the gated field-emission x-ray source, digital 2D x-ray detector and motorized object stage can synchronize x-ray exposure, data collection, objection rotation and the physiological signal of the object. The system will enable triggered and gated imaging at the rate of 1-10 millisecond (msec) per image, and will have a resolution of 30 gm or less. These capabilities, which have not been demonstrated in the current gated micro-CT systems, will provide new imaging modalities for biomedical research such as dynamic cardiac and pulmonary imaging of small animals. When fully implemented, dynamic CT images of a full cycle of cardiac motion can be obtained in 10 minutes. The new design will also significantly reduce the cost and physical size of the micro-CT scanner and thus making the technology more readily available for the research community. A substantial amount of preliminary results have been obtained and they have confirmed the validity of our hypothesis. We have also established extensive infrastructure in nanotechnology, which will be leveraged for this proposed research. We expect this proposed research will have a high degree of probability of success. In the R21 Phase (Year 1) we will design, construct and evaluate a triode-type field emission x-ray source using CNTs as the electron source. The targeted characteristics of the x-ray source are: 100-500?A tube current at 30?m resolution, 40-100KVp, programmable pulse width and repetition rate (less than 0.1 misec width at up to 10KHz) and less than 1% fluctuation in flux. We will further design and construct a field emission x-ray source with electronicallyselective variable focal spot sizes. The imaging capability and performance characteristics of the x-ray tubes will be evaluated and compared with the commercial micro-focus x-ray sources. In the R33 Phase (Year 2-4) we will assemble a dynamic micro-CT scanner using the field emission x-ray source, a commercial high-resolution fast-response digital two-dimensional x-ray detector, and cone-beam reconstruction algorithm. User interface, instrumentation control and imaging softwares will be developed. By electronically synchronizing x-ray exposure, data collection, object motion, and physiological signals, the system will enable dynamic CT imaging with high spatial and temporal resolution. After calibration we will demonstrate 1) high resolution imaging of ?ENaC transgenic mice airway to asses the relationship of survive rate to the quantity of mucus present; 2) dynamic imaging of cardiac and pulmonary motion. We have assembled a team of leading scientists and engineers in the fields of materials science, medical physics, radiology, and physiology from UNC (Zhou, Lu, Grubb, Lin and Boucher), NCSU (Lalush) and U of Iowa (Hoffman, McLennan). The research will be carried out primarily at the North Carolina Center of Nanoscale Materials at UNC where this PI is the founding director. Zhou and Lu have extensive experiences in the CNT field emission technology and are among the first to demonstrate a cold-cathode x-ray tube using the CNTs. They will be primarily responsible for the instrumentation development. Lalush will be responsible for the image reconstruction effort. Hoffman and McLennan are leading experts in the area of dynamic, volumetric cardiopulmonary CT imaging and image analysis. They will advise the CT design, compare its performance with the commercial system and use the system for dynamic imaging in a test application: smoking mouse model of emphysema. Grubb, Lin, and Boucher will utilize the CT scanner at UNC to evaluate airway pathology.