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

 描述(申请人提供)：癌症是世界上主要的死亡原因，仍然是一种难以治疗的疾病。使用纳米粒子(NPs)成像和治疗癌症是一种很有前途的方法。计算机断层扫描(CT)可以提供一种理想的成像方法来辅助开发和在临床前水平测试这些NPs。然而，目前基于能量积分探测器的CT系统对比度分辨率有限。CT成像可以通过增加光谱功能来改进。我们的主要目标是开发下一代光谱CT系统和纳米粒子，用于临床前癌症研究。为了实现这一目标，我们在我们的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，DxRay Inc.是开发光子计数X射线探测器(PCXD)的领先者。我们将追求4个具体目标。具体目标1将侧重于开发将被集成到混合微型CT系统中的多氯二苯醚。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低分辨率光谱成像链。光谱成像链将为CT数据提供多个能源箱，但空间分辨率较低。通过常规成像链，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，逐步扩大视野。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，允许在高空间分辨率下进行前所未有的光谱区分。具体目标3将专门用于NP探测器的开发。虽然我们的PCXD光谱微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)的具有高临床翻译潜力的NPs。我们将合成和表征含有碘的脂质体、金纳米颗粒(AuNPs)和血管内皮生长因子(VEGF)标记的AuNPs(VEGF-AuNPs)。最后，在具体目标4中，我们将使用新开发的光谱Micro-CT成像和VEGF-AuNPs来研究放射治疗对肉瘤肿瘤的增强作用和血管通透性的增加。我们的光谱微型CT将为将新型PCXD和算法转化为临床使用铺平道路。此外，我们的结果将确定金纳米粒子增强的放射治疗如何促进化疗进入肿瘤以提高疗效。最后，新一代光谱微型CT可以提供NPs翻译步骤所需的重要数据，产生必要的信心，将新的癌症疗法转移到患者身上。

 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.