Development of a New Generation Micro-CT imaging for Functional and Molecular Imaging of Cancer

 描述（由申请人提供）：癌症是世界上主要的死亡原因，并且仍然是一种难以治疗的疾病。使用纳米颗粒（NPs）是一种有前途的方法，可以用同一种药物成像和治疗癌症。计算机断层扫描（CT）可以提供理想的成像方法，以协助开发和测试这些纳米粒子在临床前水平。然而，基于使用能量积分探测器的当前CT系统具有有限的对比度分辨率。CT成像可以通过增加光谱能力来改善。我们的主要目标是为临床前癌症研究开发下一代光谱CT系统和NP。为了实现这一目标，我们在学术研究机构杜克大学和工业合作伙伴DxRay Inc.之间建立了合作关系。光子计数X射线探测器（PCXD）的领导者。我们将实现四个具体目标。具体目标1将侧重于开发将集成在混合微型CT系统中的PCXD。该混合系统使用基于能量积分探测器的传统高分辨率成像链和包含X射线光子计数探测器的较低分辨率光谱成像链。光谱成像链将为CT数据提供多个能量箱，但空间分辨率较低。通过常规的成像链，我们将在有限的光谱信息下实现高分辨率成像。DxRay将为PCXD提供新颖的设计，逐步增加视野。在具体目标2中，我们将开发新的算法，如光谱扩散和光谱去模糊，以实现前所未有的高空间分辨率光谱区分。具体目标3将致力于NP探针的开发。虽然我们的PCXD光谱显微CT系统应该能够基于广泛的高Z材料进行灵敏的NP成像，但我们专注于基于金（Au）和碘（I）的具有高临床转化潜力的NP。我们将合成和表征含有碘、金纳米颗粒（AuNPs）和血管内皮生长因子（VEGF）结合的AuNPs（VEGF-AuNPs）的脂质体。最后，在具体目标4中，我们将使用新开发的光谱显微CT成像和VEGF-AuNP来研究肉瘤肿瘤中放射治疗引起的增强效应和血管通透性增加。我们的光谱显微CT将为新型PCXD和算法的临床应用铺平道路。此外，我们的结果将确定金纳米粒子增强的放射疗法如何促进将化疗递送到肿瘤中以改善反应。最后，新一代光谱显微CT可以提供NP平移步骤所需的重要数据，从而产生将新的癌症疗法转移到患者身上所需的信心。

 DESCRIPTION (provided by applicant): Cancer is a leading cause of death in the world and remains a difficult disease to treat. A promising approach to image and treat cancer with the same agent is using nanoparticles (NPs). Computed tomography (CT) can offer an ideal imaging method to assist developments and test these NPs at preclinical level. However, current CT systems based on the use of energy integrating detectors, have limited contrast resolution. CT imaging can be improved by adding spectral capabilities. Our primary goal is to develop the next-generation spectral CT system and NPs for preclinical cancer research. To achieve this goal, we have established a collaboration between our academic research institution, Duke University ,and an industrial partner DxRay Inc.-a leader in developing photon-counting x-ray detectors (PCXD). We will pursue 4 specific aims. Specific aim 1 will focus on the development of PCXDs that will be integrated in a hybrid micro-CT system. The hybrid system uses a conventional high-resolution imaging chain based on an energy-integrating detector and a lower-resolution spectral imaging chain containing an x-ray photon-counting detector. The spectral imaging chain will provide multiple energy bins for the CT data, but with low spatial resolution. Through the conventional imaging chain, we will achieve high-resolution imaging with limited spectral information. DxRay will supply PCXDs with novel designs, progressively increasing the field of view. During specific aim 2, we will develop novel algorithms such as spectral diffusion and spectral deblurring allowing unprecedented spectral differentiation at high spatial resolution. Specific aim 3 will be dedicated to NP probe developments. Although our PCXD spectral micro-CT system should enable sensitive NP imaging based on a wide range of high Z-materials, we focus on NPs with high potential for clinical translation based on gold (Au) and iodine (I). We will synthesize and characterize liposomes containing iodine, gold nanoparticles (AuNPs), and vascular endothelial growth factor (VEGF)- conjugated AuNPs (VEGF-AuNPs). Finally, during specific aim 4, we will use the newly developed spectral micro-CT imaging and VEGF-AuNPs to study the augmentation effects and the increased vascular permeability caused by radiation therapy in sarcoma tumors. Our spectral micro-CT will pave the way for the translation of novel PCXDs and algorithms to clinical use. Furthermore, our results will establish how AuNPs- augmented radiation therapy can facilitate the delivery of chemotherapy into tumors to improve response. In the end, the new-generation spectral micro-CT can provide significant data required for the translational steps of NPs, generating the confidence necessary to move new cancer therapies to patients.