Abstract：
In tumor therapy anti-angiogenic approaches have the potential to increase the efficacy of a wide variety of subsequently or co-administered agents, possibly by improving or normalizing the defective tumor vasculature. Successful implementation of the concept of vascular normalization under anti-angiogenic therapy, however, mandates a detailed understanding of key characteristics and a respective scoring metric that defines an improved vasculature and thus a successful attempt. Here, we show that beyond commonly used parameters such as vessel patency and maturation, anti-angiogenic approaches largely benefit if the complex vascular network with its vessel interconnections is both qualitatively and quantitatively assessed. To gain such deeper insight the organization of vascular networks, we introduce a multi-parametric evaluation of high-resolution angiographic images based on light-sheet fluorescence microscopy images of tumors. We first could pinpoint key correlations between vessel length, straightness and diameter to describe the regular, functional and organized structure observed under physiological conditions. We found that vascular networks from experimental tumors diverted from those in healthy organs, demonstrating the dysfunctionality of the tumor vasculature not only on the level of the individual vessel but also in terms of inadequate organization into larger structures. These parameters proofed effective in scoring the degree of disorganization in different tumor entities, and more importantly in grading a potential reversal under treatment with therapeutic agents. The presented vascular network analysis will support vascular normalization assessment and future optimization of anti-angiogenic therapy.
摘要：
在肿瘤治疗中，抗血管生成方法有可能增加多种随后或共同给药的药物的功效。可能是通过改善或正常化有缺陷的肿瘤脉管系统。在抗血管生成治疗下成功实施血管正常化的概念，然而,要求详细了解关键特征和定义改善的脉管系统并因此成功尝试的相应评分指标。这里,我们表明，除了常用的参数，如血管通畅和成熟，如果对血管相互连接的复杂血管网络进行定性和定量评估,那么抗血管生成方法将在很大程度上获益.为了更深入地了解血管网络的组织，我们介绍了一种基于肿瘤光片荧光显微镜图像的高分辨率血管造影图像的多参数评估方法.我们首先可以确定血管长度之间的关键相关性，直线度和直径来描述规则，在生理条件下观察到的功能和组织结构。我们发现实验性肿瘤的血管网络从健康器官中转移出来，不仅在单个血管的水平上，而且在组织不足成较大结构方面，都证明了肿瘤血管的功能障碍。这些参数证明在不同肿瘤实体的解体程度评分方面是有效的，更重要的是在用治疗剂治疗下对潜在逆转进行分级。提出的血管网络分析将支持血管正常化评估和抗血管生成治疗的未来优化。
