The unique second wave phenomenon in contrast enhanced ultrasound imaging with nanobubbles.
The unique second wave phenomenon in contrast enhanced ultrasound imaging with nanobubbles.
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DOI：
10.1038/s41598-022-17756-1
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发表时间：
2022-08-10
影响因子：
4.6
通讯作者：
Turco, Simona
中科院分区：
文献类型：
--
作者：
Chen, Chuan;Perera, Reshani;Kolios, Michael C.;Wijkstra, Hessel;Exner, Agata A.;Mischi, Massimo;Turco, Simona
在像素级对比增强超声（CEUS）中对纳米气泡（NB）药代动力学的研究显示了一种独特的现象，其中造影剂团的第一次通过伴随着第二波。这种效应以前没有在CEUS中观察到微泡。本研究的目的是探讨这种第二波现象及其潜在的临床应用。实验中包括7只小鼠，共14个皮下植入肿瘤。在注射一团NB后，采集NB-CEUS图像以记录每个像素处的时间-强度曲线（TIC）。这些TIC拟合的药代动力学模型，我们设计来描述所观察到的第二波现象。估计的模型参数被呈现为参数图，以可视化肿瘤病变的特征。还在一只小鼠中进行组织学分析，以将肿瘤组织的分子特征与获得的参数图进行比较。从肿瘤或组织中提取的一系列基于像素的TIC中明显地显示出第二波现象。恶性肿瘤和正常组织的两个模型参数值、第二波与第一波峰值强度之比以及洗脱过程的衰减率存在较大差异（0.04 < Jessen-Shannon分歧< 0.08）。第二波的发生是我们在小鼠肿瘤和组织的NB-CEUS成像中观察到的一种独特现象。由于第二波的特征在肿瘤和组织之间是不同的，因此这种现象具有支持癌性病变的诊断的潜力。
Investigation of nanobubble (NB) pharmacokinetics in contrast-enhanced ultrasound (CEUS) at the pixel level shows a unique phenomenon where the first pass of the contrast agent bolus is accompanied by a second wave. This effect has not been previously observed in CEUS with microbubbles. The objective of this study was to investigate this second-wave phenomenon and its potential clinical applications. Seven mice with a total of fourteen subcutaneously-implanted tumors were included in the experiments. After injecting a bolus of NBs, the NB-CEUS images were acquired to record the time-intensity curves (TICs) at each pixel. These TICs are fitted to a pharmacokinetic model which we designed to describe the observed second-wave phenomenon. The estimated model parameters are presented as parametric maps to visualize the characteristics of tumor lesions. Histological analysis was also conducted in one mouse to compare the molecular features of tumor tissue with the obtained parametric maps. The second-wave phenomenon is evidently shown in a series of pixel-based TICs extracted from either tumor or tissues. The value of two model parameters, the ratio of the peak intensities of the second over the first wave, and the decay rate of the wash-out process present large differences between malignant tumor and normal tissue (0.04 < Jessen-Shannon divergence < 0.08). The occurrence of a second wave is a unique phenomenon that we have observed in NB-CEUS imaging of both mouse tumor and tissue. As the characteristics of the second wave are different between tumor and tissue, this phenomenon has the potential to support the diagnosis of cancerous lesions.
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