Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice

Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice
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DOI:
10.1172/jci34928
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发表时间:
2008-05-01
影响因子:
15.9
通讯作者:
Krishna, Murali C.
Krishna, Murali C.
中科院分区:
医学1区
文献类型:
--
作者:
Matsumoto, Shingo;Hyodo, Fuminori;Krishna, Murali C.

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实体瘤中氧分压(氧合; PO 2)的空间和时间变化的先验知识是癌症治疗结果的关键预后因素,可以大大改善放疗和化疗的治疗计划。脉冲电子顺磁共振成像(EPRI)提供活体组织PO 2的定量3D图。在这项研究中,我们实施了EPRI设置,可以在几乎真实的时间内获得2D和3D的PO 2图。我们还设计了一个结合EPRI和MRI的系统,可以在解剖学指导下生成pO(2)图。使用EPRI和空气/碳(95%O-2加5%CO2)呼吸循环,我们可视化灌注限制缺氧小鼠肿瘤。研究了肿瘤血液灌注和PO 2状态之间的关系,发现即使在显示血流的区域也存在显著的缺氧。此外,即使在含氧量正常的肿瘤区域也发现了高水平的乳酸盐,表明小鼠肿瘤中有氧糖酵解占主导地位。本报告提出了一种快速、非侵入性的方法来精确地获得肿瘤中PO 2的定量图,并结合解剖学报告。此外,该方法也可用于研究PO 2状态与肿瘤特异性表型(如有氧糖酵解)之间的关系。
A priori knowledge of spatial and temporal changes in partial pressure of oxygen (oxygenation; PO2) in solid tumors, a key prognostic factor in cancer treatment outcome, could greatly improve treatment planning in radiotherapy and chemotherapy. Pulsed electron paramagnetic resonance imaging (EPRI) provides quantitative 3D maps of tissue PO2 in living objects. In this study, we implemented an EPRI set-up that could acquire PO2 maps in almost real time for 2D and in minutes for 3D. We also designed a combined EPRI and MRI system that enabled generation of pO(2) maps with anatomic guidance. Using EPRI and an air/carbogen (95% O-2 plus 5% CO2) breathing cycle, we visualized perfusion-limited hypoxia in murine tumors. The relationship between tumor blood perfusion and PO2 status was examined, and it was found that significant hypoxia existed even in regions that exhibited blood flow. In addition, high levels of lactate were identified even in normoxic tumor regions, suggesting the predominance of aerobic glycolysis in murine tumors. This report presents a rapid, noninvasive method to obtain quantitative maps of PO2 in tumors, reported with anatomy, with precision. In addition, this method may also be useful for studying the relationship between PO2 status and tumor-specific phenotypes such as aerobic glycolysis.