Contrast-enhanced photon-counting micro-CT of tumor xenograft models.
Contrast-enhanced photon-counting micro-CT of tumor xenograft models.
复制标题
肿瘤异种移植模型的对比增强光子计数显微 CT。
DOI：
10.1101/2024.01.03.574097
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Barroso,Margarida
中科院分区：
文献类型：
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作者：
Li,Mengzhou;Guo,Xiaodong;Verma,Amit;Rudkouskaya,Alena;McKenna,AntigoneM;Intes,Xavier;Wang,Ge;Barroso,Margarida
光子计数微型计算机断层扫描（micro-CT）是小动物临床前成像的一项重大进展。基于小分子和纳米颗粒的造影剂已被广泛用于使用光子计数微CT区分肝脏肿瘤与周围组织。然而，在使用光子计数显微CT将这些市售药物应用于乳腺和卵巢肿瘤成像方面存在显著差距。在此，我们使用光子计数显微CT来确定这些造影剂在区分活的完整小鼠中的卵巢和乳腺肿瘤异种移植物方面的有效性。（AU565，MDA-MB-231和SKOV-3人癌细胞）注射ISOVUE-370（基于小分子的试剂）或Exitron Nano 12000（基于纳米颗粒的试剂），并进行光子计数显微CT。为了提高肿瘤可视化使用光子计数显微CT，我们开发了一种新的彩色可视化方法，改变色调，突出对比剂分布，提供了一个强大的替代传统的材料分解方法与较少的计算demands.Main resultsOur体内实验证实了这种彩色可视化方法的有效性，显示出不同的增强特性，为每种造影剂。定性和定量分析表明，Exitron Nano 12000提供了上级血管增强和更好的扫描定量一致性，而ISOVUE-370提供了更全面的肿瘤增强，但由于其血液半衰期短，扫描之间存在显著差异。此外，对肿瘤体积内的平均值和标准偏差值的配对t检验显示，使用基于纳米颗粒的造影剂的AU565和SKOV-3肿瘤模型之间存在显著差异（p值< 0.02），归因于其不同的血管分布，这些发现强调了光子计数显微CT在非肿瘤中的应用，这对于肿瘤表征和纵向监测肿瘤进展和对治疗的反应至关重要。
ObjectivePhoton-counting micro-computed tomography (micro-CT) is a major advance in small animal preclinical imaging. Small molecule-and nanoparticle-based contrast agents have been widely used to enable the differentiation of liver tumors from surrounding tissues using photon-counting micro-CT. However, there is a notable gap in the application of these market-available agents to the imaging of breast and ovarian tumors using photon-counting micro-CT. Herein, we have used photon-counting micro-CT to determine the effectiveness of these contrast agents in differentiating ovarian and breast tumor xenografts in live, intact mice.ApproachNude mice carrying different types of breast and ovarian tumor xenografts (AU565, MDA-MB-231 and SKOV-3 human cancer cells) were injected with ISOVUE-370 (a small molecule-based agent) or Exitron Nano 12000 (a nanoparticle-based agent) and subjected to photon-counting micro-CT. To improve tumor visualization using photon-counting micro-CT, we developed a novel color visualization method, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand.Main resultsOur in vivo experiments confirm the effectiveness of this color visualization approach, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggest that Exitron Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 delivers a more comprehensive tumor enhancement but with significant variance between scans due to its short blood half-time. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based contrast agent (p-values< 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemical analysis.SignificanceThese findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor progression and response to treatments.