Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI
Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI
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DOI：
10.1073/pnas.0908447106
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发表时间：
2009-10-20
影响因子：
11.1
通讯作者：
Krishna, Murali C.
中科院分区：
文献类型：
--
作者：
Matsumoto, Shingo;Yasui, Hironobu;Krishna, Murali C.
血管的结构和功能异常是肿瘤的常见特征。血管渗透性增加和伴随的异常血流的结果是氧气和药物的输送不良，这与治疗抵抗有关。在本研究中，我们描述了一种策略，通过使用超极化H-1-MRI（称为Over-hauser增强MRI（OMRI））和氧敏造影剂OX 63同时可视化组织氧浓度和微血管通透性。动态核极化（DNP）诱导实质性MRI信号增强。与在热平衡状态下相比，DNP在1.5mM的OX 63浓度下实现了MRI信号的高达7，000%的增加。超极化的程度主要受OX 63的局部浓度的影响，而受组织氧水平的影响相反。通过收集不同超极化水平的动态OMRI图像，可以同时确定OX 63的局部氧浓度和微血管通透性。将这种模式应用于小鼠肿瘤揭示了具有高血管通透性的肿瘤区域与缺氧在时空上一致。对来自个体动物的图像数据的定量分析显示肿瘤血管渗漏和中值氧浓度之间呈负相关。在OMRI实验后从相同动物获得的肿瘤组织的免疫组织化学分析表明，肿瘤血管缺乏完整性与肿瘤微血管通透性增加相关。这种双重成像技术可用于纵向评估肿瘤血管功能和氧合对化疗、放疗或抗血管生成治疗的反应。
Architectural and functional abnormalities of blood vessels are a common feature in tumors. A consequence of increased vascular permeability and concomitant aberrant blood flow is poor delivery of oxygen and drugs, which is associated with treatment resistance. In the present study, we describe a strategy to simultaneously visualize tissue oxygen concentration and microvascular permeability by using a hyperpolarized H-1-MRI, known as Over-hauser enhanced MRI (OMRI), and an oxygen-sensitive contrast agent OX63. Substantial MRI signal enhancement was induced by dynamic nuclear polarization (DNP). The DNP achieved up to a 7,000% increase in MRI signal at an OX63 concentration of 1.5 mM compared with that under thermal equilibrium state. The extent of hyperpolarization is influenced mainly by the local concentration of OX63 and inversely by the tissue oxygen level. By collecting dynamic OMRI images at different hyperpolarization levels, local oxygen concentration and microvascular permeability of OX63 can be simultaneously determined. Application of this modality to murine tumors revealed that tumor regions with high vascular permeability were spatio- temporally coincident with hypoxia. Quantitative analysis of image data from individual animals showed an inverse correlation between tumor vascular leakage and median oxygen concentration. Immunohistochemical analyses of tumor tissues obtained from the same animals after OMRI experiments demonstrated that lack of integrity in tumor blood vessels was associated with increased tumor microvascular permeability. This dual imaging technique may be useful for the longitudinal assessment of changes in tumor vascular function and oxygenation in response to chemotherapy, radiotherapy, or anti-angiogenic treatment.