Department of Tumor Biology and Angiogenesis, South San Francisco, CA 94080, USA.
Magn Reson Med. 2011 Mar;65(3):889-99. doi: 10.1002/mrm.22880.
Imaging of tumor microvasculature has become an important tool for studying angiogenesis and monitoring antiangiogenic therapies. Ultrasmall paramagnetic iron oxide contrast agents for indirect imaging of vasculature offer a method for quantitative measurements of vascular biomarkers such as vessel size index, blood volume, and vessel density (Q). Here, this technique is validated with direct comparisons to ex vivo micro-computed tomography angiography and histologic vessel measurements, showing significant correlations between in vivo vascular MRI measurements and ex vivo structural vessel measurements. The sensitivity of the MRI vascular parameters is also demonstrated, in combination with a multispectral analysis technique for segmenting tumor tissue to restrict the analysis to viable tumor tissue and exclude regions of necrosis. It is shown that this viable tumor segmentation increases sensitivity for detection of significant effects on blood volume and Q by two antiangiogenic therapeutics [anti-vascular endothelial growth factor (anti-VEGF) and anti-neuropilin-1] on an HM7 colorectal tumor model. Anti-vascular endothelial growth factor reduced blood volume by 36±3% (p<0.0001) and Q by 52±3% (p<0.0001) at 48 h post-treatment; the effects of anti-neuropilin-1 were roughly half as strong with a reduction in blood volume of 18±6% (p<0.05) and a reduction in Q of 33±5% (p<0.05) at 48 h post-treatment.
肿瘤微血管成像已成为研究血管生成和监测抗血管生成治疗的重要工具。超顺磁氧化铁对比剂可间接对血管成像，为血管生物标志物（如血管大小指数、血容量和血管密度（Q））的定量测量提供了一种方法。在此，通过与离体 micro-CT 血管造影和组织学血管测量的直接比较来验证该技术，结果显示体内血管 MRI 测量与离体结构血管测量之间具有显著相关性。还证明了 MRI 血管参数的敏感性，结合用于分割肿瘤组织的多光谱分析技术，将分析限制在存活的肿瘤组织内，并排除坏死区域。结果表明，这种对存活肿瘤组织的分割增加了对两种抗血管生成治疗药物（抗血管内皮生长因子（anti-VEGF）和抗神经纤毛蛋白-1）对 HM7 结直肠肿瘤模型的血容量和 Q 产生显著影响的检测敏感性。抗血管内皮生长因子在治疗后 48 小时内使血容量减少 36±3%（p<0.0001），Q 值减少 52±3%（p<0.0001）；抗神经纤毛蛋白-1 的作用大约减半，血容量减少 18±6%（p<0.05），Q 值减少 33±5%（p<0.05），在治疗后 48 小时。
