Furman-Haran E, Margalit R, Grobgeld D, Degani H
Department of Chemical Physics, Weizmann Institute of Science, Rehovot, Israel.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6247-51. doi: 10.1073/pnas.93.13.6247.
The mechanism of contrast enhancement of tumors using magnetic resonance imaging was investigated in MCF7 human breast cancer implanted in nude mice. Dynamic contrast-enhanced images recorded at high spatial resolution were analyzed by an image analysis method based on a physiological model, which included the blood circulation, the tumor, the remaining tissues, and clearance via the kidneys. This analysis enabled us to map in rapidly enhancing regions within the tumor, the capillary permeability factor (capillary permeability times surface area per voxel volume) and the fraction of leakage space. Correlation of these maps with T2-weighted spin echo images, with histopathology, and with immunohistochemical staining of endothelial cells demonstrated the presence of dense permeable microcapillaries in the tumor periphery and in intratumoral regions that surrounded necrotic loci. The high leakage from the intratumoral permeable capillaries indicated an induction of a specific angiogenic process associated with stress conditions that cause necrosis. This induction was augmented in tumors responding to tamoxifen treatment. Determination of the distribution and extent of this stress-induced angiogenic activity by contrast-enhanced MRI might be of diagnostic and of prognostic value.
在植入裸鼠的MCF7人乳腺癌模型中，研究了利用磁共振成像增强肿瘤对比度的机制。通过基于生理模型的图像分析方法，对以高空间分辨率记录的动态对比增强图像进行分析，该生理模型包括血液循环、肿瘤、其余组织以及经肾脏的清除过程。这种分析使我们能够在肿瘤内快速增强的区域绘制毛细血管渗透因子（毛细血管渗透率乘以每体素体积的表面积）和渗漏空间分数图。这些图与T2加权自旋回波图像、组织病理学以及内皮细胞免疫组化染色的相关性表明，在肿瘤周边以及围绕坏死灶的瘤内区域存在密集的渗透性微毛细血管。瘤内渗透性毛细血管的高渗漏表明存在与导致坏死的应激条件相关的特定血管生成过程的诱导。在对他莫昔芬治疗有反应的肿瘤中，这种诱导作用增强。通过对比增强MRI确定这种应激诱导的血管生成活性的分布和程度可能具有诊断和预后价值。
