Imaging the extracellular pH of tumors by MRI after injection of a single cocktail of T1 and T2 contrast agents.
Imaging the extracellular pH of tumors by MRI after injection of a single cocktail of T1 and T2 contrast agents.
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DOI：
10.1002/nbm.1701
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发表时间：
2011-12
影响因子：
2.9
通讯作者：
Gillies, Robert J.
中科院分区：
文献类型：
--
作者：
Martinez, Gary V.;Zhang, Xiaomeng;Garcia-Martin, Maria L.;Morse, David L.;Woods, Mark;Sherry, A. Dean;Gillies, Robert J.
实体瘤的细胞外pH（pHe）呈酸性，有证据表明酸性pHe与侵袭性有关。在此，我们描述了一种 MRI 单次输注方法 (SIM)，使用造影剂混合物 (CA) 测量神经胶质瘤中的 pHe。该混合物含有 Gd-DOTA-4AmP 和 Dy-DOTP，它们对放松的影响分别对 pH 值敏感和不敏感。 Gd-CA 主导自旋晶格弛豫率 ΔR1，而 Dy-CA 主导自旋-自旋弛豫率 。这些效应用于确定 [Dy] 的像素浓度，进而用于计算 [Gd] 浓度值。该值用于将 ΔR1 值转换为摩尔弛豫率 Δr1，从而转换为 pHe 图。该方法的开发涉及大鼠脑胶质瘤模型的体内校准和测量。校准阶段包括使用回波平面光谱成像 (EPSI) 和 T1 加权图像确定 ΔR1 和由两种 pH 独立 CA（Gd-DTPA 和 Dy-DOTP）诱导的ΔR1 之间的定量关系。 EPSI 图像中水峰的强度和线宽受 CA 影响，可用于跟踪药代动力学。这些数据显示了用于 CA 浓度测定的内球和外球弛豫率常数之间的线性关系。观察到关系斜率的非线性，并将其归因于血管通透性的变化。在 pHe 测量阶段，注入 Gd-DOTA-4AmP 代替 Gd-DTPA，并通过交错 T1 加权图像 (R1) 和 EPSI () 的组合获得弛豫率。由此产生的 r1 值产生了具有高空间分辨率的 pHe 图。
The extracellular pH (pHe) of solid tumors is acidic, and there is evidence that acidic pHe is related to invasiveness. Herein, we describe an MRI single infusion method (SIM) to measure pHe in gliomas using a cocktail of contrast agents (CA). The cocktail contained Gd-DOTA-4AmP and Dy-DOTP, whose effects on relaxation are sensitive and insensitive to pH, respectively. The Gd-CA dominated the spin-lattice relaxivity, ΔR1, whereas the Dy-CA dominated the spin-spin relaxivity, . The effects were used to determine the pixelwise concentration of [Dy] which, in turn, were used to calculate a value for [Gd] concentration. This value was used to convert ΔR1 values to molar relaxivity, Δr1 and hence, pHe maps. Development of the method involved in vivo calibration and measurements in a rat brain glioma model. The calibration phase consisted of determining a quantitative relationship between the ΔR1 and induced by two pH-independent CAs, Gd-DTPA and Dy-DOTP, using Echo Planar Spectroscopic Imaging (EPSI) and T1 weighted images. Intensity and linewidths of the water peaks in EPSI images were affected by CA and were used to follow pharmacokinetics. These data showed a linear relationship between inner- and outer-sphere relaxation rate constants that were used for CA concentration determination. Non-linearity in the slope of the relationship was observed and ascribed to variations in vascular permeability. In the pHe measurement phase, Gd-DOTA-4AmP was infused instead of Gd-DTPA, and relaxivities were obtained through the combination of interleaved T1-weighted images (R1) and EPSI for (). The resulting r1 values yielded pHe maps with high spatial resolution.
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影响因子：
3.3
作者：
YABLONSKIY, DA;HAACKE, EM
通讯作者：
HAACKE, EM
影响因子：
2.5
作者：
Vincensini, D;Dedieu, V;Joffre, F
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影响因子：
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作者：
Dimicoli, JL;Patry, J;Volk, A
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Volk, A
影响因子：
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作者：
Du, WL;Fan, XB;Karczmar, GS
通讯作者：
Karczmar, GS
影响因子：
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作者：
Kalman, Ferenc K.;Woods, Mark;Sherry, A. Dean
通讯作者：
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