Tumor perfusion in small animals with tomographic digital subtraction angiography

描述(申请人提供)：啮齿类动物肿瘤血管的体内成像可以提供关于肿瘤发展和治疗效果的宝贵信息。由于对高空间和时间分辨率的综合要求，体内精细的微血管结构和功能成像对现有的小动物成像技术包括Micro-CT和Micro-MRI提出了挑战。我们建议使用断层数字减影血管造影术(TDSA)来评估小动物肿瘤的血流灌注。TDSA结合了数字减影血管造影(DSA)的高时间分辨率和Micro-CT的高空间分辨率的优点。TDSA通过使用断层合成和CT重建算法提供三维信息来增强投影成像方法，例如DSA。TDSA方法基于一种新的范式，即在一系列不同的旋转角度下，在多次连续注射微L体积的对比剂时可以再现相同的时间密度曲线。我们将建立一个带有两个管/探测器的TDSA系统，以提供时间分辨率为100毫秒、空间分辨率为100微米至1毫米的4D成像数据。这意味着时间分辨率提高了10倍，比用于小动物的灌注成像的最先进的临床前微型CT系统实现的分辨率至少高出两倍。TDSA的能力将在大鼠和小鼠的肿瘤生理学研究中建立。TDSA灌注测量将使用动态体模和利用微球和血管染色的技术进行校准和验证。我们将TDSA与传统的Micro-CT相结合，使用常规和血池碘造影剂的组合，为肿瘤的血流灌注、渗透性和3D血管结构的特征提供一个标准化的方案。TDSA将提供4D功能成像方法，能够达到在小动物上进行肿瘤生理学研究和抗血管生成药物评估所需的非常高的时间和空间分辨率。

DESCRIPTION (provided by applicant): The in-vivo imaging of tumor vasculature in rodents can provide invaluable information about tumor development and treatment efficacy. Imaging in vivo fine micro-vascular structure and function presents a challenge to existing small animal imaging techniques including micro-CT and micro-MRI due to combined requirements for high spatial and temporal resolution. We propose the use of Tomographic Digital Subtraction Angiography (TDSA) for estimation of tumor perfusion in small animals. TDSA combines the advantages of high temporal resolution of digital subtraction angiography (DSA) and high spatial resolution of micro-CT. TDSA augments projection imaging methods such as DSA by providing three-dimensional information using tomosynthesis and CT reconstruction algorithms. TDSA approach is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of microL volumes of contrast at a series of different angles of rotation. We will build a TDSA system with two tubes/detectors to provide data for 4D imaging with a temporal resolution on the order of 100 ms and spatial resolution ranging from 100 microns to 1 mm. This represents a ten fold increase in temporal resolution and at least two times higher resolution than those achieved by the state of the art pre-clinical micro-CT systems used in perfusion imaging in small animals. The capabilities of TDSA will be established in studies on tumor physiology in both rats and mice. TDSA perfusion measures will be calibrated and validated using a dynamic phantom and techniques exploiting microspheres and vascular staining. We will integrate TDSA with conventional micro-CT to provide a standardized protocol for characterization of tumor perfusion, permeability and 3D vascular architecture, using a combination of conventional and blood pool iodinated contrast agents. TDSA will provide the 4D functional imaging method capable of achieving the very high temporal and spatial resolution required for studies on tumor physiology and evaluation of anti-angiogenic drugs on small animals.