de Bazelaire C, Calmon R, Chapellier M, Pluvinage A, Frija J, de Kerviler E
Service de Radiologie, Hôpital Saint-Louis, 1 Avenue Claude-Vellefaux, 75010 Paris, France.
Bull Cancer. 2010 Jan;97(1):79-90. doi: 10.1684/bdc.2010.0961.
Angiogenesis is the process of activating dormant endothelial cells to form new vessels, after stimulation and it is essential in tumor growth. In many types of cancer, angiogenesis results from the activation of oncogenes that stimulate the production of Vascular Endothelial Growth Factor (VEGF). However, these newly formed vessels have a great number of abnormalities: increased density of fragile and hyper-permeable microvessels, arterial-venous shunts, caliber abnormalities and flow instabilities susceptible to flow direction inversion according to interstitial pressure. Anti-angiogenic treatments inhibit VEGF activity, perceived as structural and functional normalization of the microvascular pattern, such as reduced density of microvessels and restored morphology of the remaining ones. Conventional imaging techniques are not sensible to these changes, at best they show tumor size stabilization, hence the need of new techniques. Microvascularization imaging can be achieved by detecting functional disturbances to blood flow and not by showing the microvasculature per se. These techniques are based in quantifying the enhancement in tumor due to the passage of contrast agent after injection or protons labeled by a magnetic field. Through these measurements, one can derive interstitial and blood volumes as well as the tissue perfusion and capillary wall permeability. Microvascular imaging has greatly benefited from the improvements seen in CT and MRI equipment allowing large volume coverage with high spatial and temporal resolutions as from the evolutions in the methods to calculate, present and compare maps of the microcirculation and it's heterogeneity. However, software to analyze microvascularization are still rare, limiting the technique's application and validation in large scale. Nevertheless, imaging of the microcirculation is useful throughout the care of the oncological patient: it can reinforce the suspicious nature of a lesion, suggest anti-angiogenic treatment efficacy in hypervascular lesions, and show early treatment response before morphological changes as in RECIST criteria.
血管生成是指在受到刺激后激活休眠的内皮细胞以形成新血管的过程,它在肿瘤生长中至关重要。在许多类型的癌症中,血管生成是由刺激血管内皮生长因子(VEGF)产生的癌基因激活所致。然而,这些新形成的血管存在大量异常:脆弱且高通透性微血管的密度增加、动静脉分流、管径异常以及血流不稳定,易根据间质压力发生血流方向反转。抗血管生成治疗可抑制VEGF活性,被视为微血管模式的结构和功能正常化,如微血管密度降低以及剩余微血管形态恢复。传统成像技术对这些变化不敏感,充其量只能显示肿瘤大小稳定,因此需要新技术。微血管成像可通过检测血流功能障碍来实现,而非直接显示微血管本身。这些技术基于量化注射造影剂后或经磁场标记的质子通过肿瘤时的增强情况。通过这些测量,可以得出间质和血容量以及组织灌注和毛细血管壁通透性。微血管成像极大地受益于CT和MRI设备的改进,这些设备能够以高空间和时间分辨率实现大体积覆盖,这也得益于计算、呈现和比较微循环及其异质性图谱的方法的发展。然而,用于分析微血管生成的软件仍然很少,限制了该技术在大规模应用和验证中的应用。尽管如此,微循环成像在肿瘤患者的整个治疗过程中都很有用:它可以强化病变的可疑性质,提示抗血管生成治疗对高血管病变的疗效,并在出现RECIST标准中的形态学变化之前显示早期治疗反应。