Model free approach to kinetic analysis of real-time hyperpolarized 13C magnetic resonance spectroscopy data.
Model free approach to kinetic analysis of real-time hyperpolarized 13C magnetic resonance spectroscopy data.
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DOI：
10.1371/journal.pone.0071996
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Eykyn TR
中科院分区：
文献类型：
--
作者：
Hill DK;Orton MR;Mariotti E;Boult JK;Panek R;Jafar M;Parkes HG;Jamin Y;Miniotis MF;Al-Saffar NM;Beloueche-Babari M;Robinson SP;Leach MO;Chung YL;Eykyn TR
实时检测代谢通量的速率，或内源性酶反应的交换速率，现在在生物系统中使用动态核磁共振是可行的。从该技术推导反应速率动力学通常需要动态数据的多房室模型，因此结果依赖于模型并且易于误解。我们提出了一个无模型公式的基础上的总面积下的曲线（AUC）的注射和产品代谢产物，例如丙酮酸和乳酸的比例。一个理论框架，以支持这种新的分析方法进行了描述，并证明了AUC比是成比例的前向速率常数k。我们表明，无模型方法与一系列癌细胞系的全细胞体外实验的k密切相关，并以相当或更高的灵敏度检测用泛I类PI 3 K抑制剂GDC-0941处理的细胞中的反应。在荷瘤异种移植物小鼠体内、对照肿瘤中以及用二氯乙酸盐进行药物治疗后观察到相同的结果。一个重要的发现是，曲线下面积与输入函数和注射代谢物产生的任何其他代谢途径无关。这种无模型方法为人体超极化13 C代谢成像的临床转化中基于动力学模型的速率测量提供了一种稳健且临床相关的替代方案，其中输入函数的测量可能存在问题。
Real-time detection of the rates of metabolic flux, or exchange rates of endogenous enzymatic reactions, is now feasible in biological systems using Dynamic Nuclear Polarization Magnetic Resonance. Derivation of reaction rate kinetics from this technique typically requires multi-compartmental modeling of dynamic data, and results are therefore model-dependent and prone to misinterpretation. We present a model-free formulism based on the ratio of total areas under the curve (AUC) of the injected and product metabolite, for example pyruvate and lactate. A theoretical framework to support this novel analysis approach is described, and demonstrates that the AUC ratio is proportional to the forward rate constant k. We show that the model-free approach strongly correlates with k for whole cell in vitro experiments across a range of cancer cell lines, and detects response in cells treated with the pan-class I PI3K inhibitor GDC-0941 with comparable or greater sensitivity. The same result is seen in vivo with tumor xenograft-bearing mice, in control tumors and following drug treatment with dichloroacetate. An important finding is that the area under the curve is independent of both the input function and of any other metabolic pathways arising from the injected metabolite. This model-free approach provides a robust and clinically relevant alternative to kinetic model-based rate measurements in the clinical translation of hyperpolarized 13C metabolic imaging in humans, where measurement of the input function can be problematic.
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DOI：
10.1016/s0360-3016(96)00244-1
发表时间：
1996-08-01
影响因子：
7
作者：
HaasKogan, DA;Yount, G;Israel, MA
通讯作者：
Israel, MA
通过超极化 13 C NMR 分析丙酮酸与乳酸交换的动力学模型的比较。
影响因子：
2.9
作者：
Harrison, Crystal;Yang, Chendong;Jindal, Ashish;DeBerardinis, Ralph J.;Hooshyar, M. A.;Merritt, Matthew;Sherry, A. Dean;Malloy, Craig R.
通讯作者：
Malloy, Craig R.
影响因子：
3.3
作者：
Keshari, Kayvan R.;Kurhanewicz, John;Jeffries, Rex E.;Wilson, David M.;Dewar, Brian J.;Van Criekinge, Mark;Zierhut, Matthew;Vigneron, Daniel B.;Macdonald, Jeffrey M.
通讯作者：
Macdonald, Jeffrey M.
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Seth, Pankaj;Grant, Aaron;Sukhatme, Vikas P.
通讯作者：
Sukhatme, Vikas P.