A comparison of quantitative methods for clinical imaging with hyperpolarized 13C-pyruvate

A comparison of quantitative methods for clinical imaging with hyperpolarized 13C-pyruvate
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DOI:
10.1002/nbm.3468
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发表时间:
2016-04-01
期刊:
影响因子:
2.9
通讯作者:
Gallagher, Ferdia A.
Gallagher, Ferdia A.
中科院分区:
医学3区
文献类型:
--
作者:
Daniels, Charlie J.;McLean, Mary A.;Gallagher, Ferdia A.

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溶解动态核极化(DNP)使得超极化C-13标记分子的代谢(例如[1-C-13]丙酮酸盐转化为[1-C-13]乳酸盐)能够在组织中动态且非侵入性地成像。在动物模型中,这种交换反应的成像已被证明可以检测早期治疗反应并与肿瘤分级相关。最近完成了第一项人类DNP研究,为了广泛的临床转化,需要简单可靠的方法来准确探测患者的反应。然而,目前还没有达成共识的最适当的方法来量化这种交换反应。在这项研究中,在体外系统被用来比较几种动力学模型,以及简单的无模型方法。实验使用临床超极化仪、人体3 T MR系统和光谱成像序列进行。通过使用大鼠皮下乳腺肿瘤在体内比较定量方法,以检查丙酮酸流入的影响。双向动力学模型是表征体外交换反应的最准确的方法,并且Heaviside步骤流入曲线的并入能够最好地描述体内数据。乳酸达峰时间和乳酸-丙酮酸曲线下面积比是简单的无模型方法,可准确代表完整反应,达峰时间方法在最佳动力学模型中的表现无可争议。最后,从单个像素提取数据是整个感兴趣区域的鲁棒且可靠的替代。这项工作已经确定了适当的定量方法,为未来的工作在分析人类超极化的C-13数据。(c)2016作者NMR in Biomedicine,John Wiley & Sons Ltd.
Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized C-13-labelled molecules, such as the conversion of [1-C-13]pyruvate to [1-C-13]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized C-13 data. (c) 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.