Pulse sequence considerations for quantification of pyruvate-to-lactate conversion kPL in hyperpolarized 13C imaging
Pulse sequence considerations for quantification of pyruvate-to-lactate conversion kPL in hyperpolarized 13C imaging
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DOI：
10.1002/nbm.4052
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发表时间：
2019-03-01
影响因子：
2.9
通讯作者：
Larson, Peder E. Z.
中科院分区：
文献类型：
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作者：
Chen, Hsin-Yu;Gordon, Jeremy W.;Larson, Peder E. Z.
超极化的C-13MRI利用前所未有的50000倍的信噪比增强来询问患者和动物的癌症代谢。它可以测量丙酮酸到乳酸的转化率k(PL)，这是癌症侵袭性和进展的代谢生物标志物。因此，可靠地计算k(Pl)是至关重要的。在这项研究中，通过使用几个特殊设计的脉冲序列，在模型模拟和活体动物研究中识别和研究了调节k(PL)估计的三个序列分量和参数。这些因素包括射频脉冲引起的磁化破坏效应、破碎机梯度引起的流动抑制以及松弛引起的固有图像加权。模拟结果表明，采用无输入k(PL)拟合法可以显著改善射频诱导的磁化损伤。体内研究发现，具有导致流动抑制的附加梯度的表观k(PL)显著更高(k(PL，FID-Delay，Crush)/k(PL，FID-Delay)=1.37+/-0.33，P<；0.01，N=6)，这与模拟结果(12.5%的k(PL)误差，Delta v=40 cm/S)一致，表明梯度主要抑制流动的丙酮酸自旋。与最小T-E版本(k(PL，FID-Delay)/k(PL，FID)=0.67+/-0.09，P<；0.01，N=5)相比，延迟自由诱导衰变(FID)采集法的k(PL)显著降低，并且乳酸峰的线宽比丙酮酸峰宽(Delta omega(乳酸)/Delta omega(丙酮酸)=1.32+/-0.07，P<；0.000 01，N=13)。这说明乳酸的T-2*比丙酮酸的T-2*短，会影响计算的k(PL)值。我们还发现，与双自旋回波序列相比，FID序列产生的k(PL)显著更低(P<；0.0001，N=7)，双自旋回波序列包括自旋回波破坏、来自破碎机梯度的流动抑制和更多的T-2加权(k(PL，DSE)/k(PL，FID)=2.4+/-0.98，P<；0.0001，N=7)。总之，脉冲序列及其与药代动力学和组织微环境的相互作用可以影响和优化k(PL)的测量。数据采集和分析管道可以协同工作，为未来的临床前和临床研究提供更强大和更具重复性的k(PL)指标。
Hyperpolarized C-13 MRI takes advantage of the unprecedented 50 000-fold signal-to-noise ratio enhancement to interrogate cancer metabolism in patients and animals. It can measure the pyruvate-to-lactate conversion rate, k(PL), a metabolic biomarker of cancer aggressiveness and progression. Therefore, it is crucial to evaluate k(PL) reliably. In this study, three sequence components and parameters that modulate k(PL) estimation were identified and investigated in model simulations and through in vivo animal studies using several specifically designed pulse sequences. These factors included a magnetization spoiling effect due to RF pulses, a crusher gradient-induced flow suppression, and intrinsic image weightings due to relaxation. Simulation showed that the RF-induced magnetization spoiling can be substantially improved using an inputless k(PL) fitting. In vivo studies found a significantly higher apparent k(PL) with an additional gradient that leads to flow suppression (k(PL,FID-Delay,Crush)/k(PL,FID-Delay) = 1.37 +/- 0.33, P < 0.01, N = 6), which agrees with simulation outcomes (12.5% k(PL) error with Delta v = 40 cm/s), indicating that the gradients predominantly suppressed flowing pyruvate spins. Significantly lower k(PL) was found using a delayed free induction decay (FID) acquisition versus a minimum-T-E version (k(PL,FID-Delay)/k(PL,FID) = 0.67 +/- 0.09, P < 0.01, N = 5), and the lactate peak had broader linewidth than pyruvate (Delta omega(lactate)/Delta omega(pyruvate) = 1.32 +/- 0.07, P < 0.000 01, N = 13). This illustrated that lactate's T-2*, shorter than that of pyruvate, can affect calculated k(PL) values. We also found that an FID sequence yielded significantly lower k(PL) versus a double spin-echo sequence that includes spin-echo spoiling, flow suppression from crusher gradients, and more T-2 weighting (k(PL,DSE)/k(PL,FID) = 2.40 +/- 0.98, P < 0.0001, N = 7). In summary, the pulse sequence, as well as its interaction with pharmacokinetics and the tissue microenvironment, can impact and be optimized for the measurement of k(PL). The data acquisition and analysis pipelines can work synergistically to provide more robust and reproducible k(PL) measures for future preclinical and clinical studies.