Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations.
Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations.
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发表时间：
2001-04
期刊：
影响因子：
11.2
通讯作者：
M. Gee;H. M. Saunders;James Lee;J. Sanzo;W. T. Jenkins;S. Evans;G. Trinchieri;C. Sehgal;Michael D. Feldman;William Lee
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文献类型：
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作者：
M. Gee;H. M. Saunders;James Lee;J. Sanzo;W. T. Jenkins;S. Evans;G. Trinchieri;C. Sehgal;Michael D. Feldman;William Lee
通过重组白细胞介素12治疗的小鼠肿瘤的连续功率多普勒超声成像对抗血管生成治疗进行无创监测，其结果与显微镜下肿瘤血管分布的评估相关。治疗抑制了已建立的K1735肿瘤的生长，但未抑制IFN-γ无应答的K1735.N23变体的生长。治疗期间K1735肿瘤血管的连续多普勒成像显示了从弥漫性灌注模式到更点状分布的渐进性变化。图像的定量分析显示，代表整体肿瘤灌注的彩色加权分数平均值在这些肿瘤中持续降低，主要是因为携带血流的肿瘤横截面积分数降低。相比之下，这些参数在治疗期间无反应的肿瘤中增加。厚肿瘤切片的共聚焦显微镜显示，在有效治疗的荧光染料结合凝集素标记的血管在体内的密度和分支减少。薄肿瘤切片的免疫组织学检查证实了成功治疗的小血管优先损失。在重组白细胞介素12治疗其他两种反应性小鼠肿瘤类型期间，也观察到肿瘤血管解剖和灌注的类似变化。这些结果表明，能量多普勒超声是一种敏感的，非侵入性的方法，用于报告治疗引起的血管解剖结构变化的功能后果，可用于连续监测肿瘤灌注和抗血管治疗的疗效在临床试验中。
Noninvasive monitoring of antiangiogenic therapy was performed by serial power Doppler ultrasound imaging of murine tumors treated with recombinant interleukin 12, the results of which were correlated with assessments of tumor vascularity by microscopy. Growth of established K1735 tumors, but not of IFN-gamma-unresponsive K1735.N23 variants, was suppressed by treatment. Serial Doppler imaging of K1735 tumor vascularity during treatment revealed a progressive change from a diffuse perfusion pattern to a more punctate distribution. Quantitative analysis of the images revealed that color-weighted fractional average, representing overall tumor perfusion, consistently decreased in these tumors, primarily because of a decrease in fractional tumor cross-sectional area carrying blood flow. In contrast, these parameters increased in nonresponsive tumors during treatment. Confocal microscopy of thick tumor sections revealed a reduction in the density and arborization of vessels labeled in vivo by fluorochrome-conjugated lectin with effective treatment. Immunohistological examination of thin tumor sections confirmed the preferential loss of small vessels with successful therapy. Similar changes in tumor vascular anatomy and perfusion were also observed during recombinant interleukin 12 treatment of two other responsive murine tumor types. These results indicate that power Doppler ultrasound is a sensitive, noninvasive method for reporting functional consequences of therapy-induced vascular anatomical changes that can be used to serially monitor tumor perfusion and efficacy of antivascular therapy in clinical trials.