UCL Centre for Advanced Biomedical Imaging, Division of Medicine, London, UK.
Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, UK.
Cancer Res. 2018 Apr 1;78(7):1859-1872. doi: 10.1158/0008-5472.CAN-17-1546. Epub 2018 Jan 9.
Several distinct fluid flow phenomena occur in solid tumors, including intravascular blood flow and interstitial convection. Interstitial fluid pressure is often raised in solid tumors, which can limit drug delivery. To probe low-velocity flow in tumors resulting from raised interstitial fluid pressure, we developed a novel MRI technique named convection-MRI, which uses a phase-contrast acquisition with a dual-inversion vascular nulling preparation to separate intra- and extravascular flow. Here, we report the results of experiments in flow phantoms, numerical simulations, and tumor xenograft models to investigate the technical feasibility of convection-MRI. We observed a significant correlation between estimates of effective fluid pressure from convection-MRI with gold-standard, invasive measurements of interstitial fluid pressure in mouse models of human colorectal carcinoma. Our results show how convection-MRI can provide insights into the growth and responsiveness to vascular-targeting therapy in colorectal cancers. A noninvasive method for measuring low-velocity fluid flow caused by raised fluid pressure can be used to assess changes caused by therapy. .
实体瘤中存在几种不同的流体流动现象,包括血管内血流和间质对流。实体瘤中间质流体压力常常升高,这会限制药物输送。为了探测由升高的间质流体压力引起的肿瘤中的低速流动,我们开发了一种新的 MRI 技术,称为对流 MRI,该技术使用具有双反转血管零化准备的相位对比采集来分离血管内和血管外的流动。在这里,我们报告了在流动模型、数值模拟和肿瘤异种移植模型中的实验结果,以研究对流 MRI 的技术可行性。我们观察到从对流 MRI 对有效流体压力的估计与在人结直肠癌的小鼠模型中对间质流体压力的金标准、侵入性测量之间存在显著相关性。我们的结果表明,对流 MRI 如何提供对结直肠癌生长和对血管靶向治疗的反应性的深入了解。用于测量由升高的流体压力引起的低速流体流动的非侵入性方法可用于评估治疗引起的变化。