Hu Xiaowen, Caskey Charles F, Mahakian Lisa M, Kruse Dustin E, Beegle Julie R, Declèves Anne-Emilie, Rychak Joshua J, Sutcliffe Patrick L, Sharma Kumar, Ferrara Katherine W
Department of Biomedical Engineering, University of California, Davis One Shields Ave, Davis, CA 95616, USA.
Am J Nucl Med Mol Imaging. 2013 Jul 10;3(4):336-49. Print 2013.
Ultrasound can selectively and specifically visualize upregulated vascular receptors through the detection of bound microbubbles. However, most current ultrasound molecular imaging methods incur delays that result in longer acquisition times and reduced frame rates. These delays occur for two main reasons: 1) multi-pulse imaging techniques are used to differentiate microbubbles from tissue and 2) acquisition occurs after free bubble clearance (>6 minutes) in order to differentiate bound from freely circulating microbubbles. In this paper, we validate tumor imaging with a broadband single pulse molecular imaging method that is faster than the multi-pulse methods typically implemented on commercial scanners. We also combine the single pulse method with interframe filtering to selectively image targeted microbubbles without waiting for unbound bubble clearance, thereby reducing acquisition time from 10 to 2 minutes. The single pulse imaging method leverages non-linear bubble behavior by transmitting at low and receiving at high frequencies (TLRH). We implemented TLRH imaging and visualized the accumulation of intravenously administrated integrin-targeted microbubbles in a phantom and a Met-1 mouse tumor model. We found that the TLRH contrast imaging has a ~2-fold resolution improvement over standard contrast pulse sequencing (CPS) imaging. By using interframe filtering, the tumor contrast was 24.8±1.6 dB higher after the injection of integrin-targeted microbubbles than non-targeted control MBs, while echoes from regions lacking the target integrin were suppressed by 26.2±2.1 dB as compared with tumor echoes. Since real-time three-dimensional (3D) molecular imaging provides a more comprehensive view of receptor distribution, we generated 3D images of tumors to estimate their volume, and these measurements correlated well with expected tumor sizes. We conclude that TLRH combined with interframe filtering is a feasible method for 3D targeted ultrasound imaging that is faster than current multi-pulse strategies.
超声可通过检测结合的微泡，选择性、特异性地显示上调的血管受体。然而，当前大多数超声分子成像方法存在延迟，导致采集时间延长且帧率降低。这些延迟主要有两个原因：1）使用多脉冲成像技术来区分微泡与组织；2）在游离气泡清除后（>6分钟）进行采集，以区分结合的微泡与自由循环的微泡。在本文中，我们验证了一种宽带单脉冲分子成像方法用于肿瘤成像，该方法比商业扫描仪上通常采用的多脉冲方法更快。我们还将单脉冲方法与帧间滤波相结合，无需等待未结合气泡清除即可选择性地对靶向微泡成像，从而将采集时间从10分钟减少到2分钟。单脉冲成像方法通过低频发射和高频接收（TLRH）利用了非线性气泡行为。我们实施了TLRH成像，并在体模和Met-1小鼠肿瘤模型中观察到静脉注射的整合素靶向微泡的聚集。我们发现，TLRH对比成像比标准对比脉冲序列（CPS）成像的分辨率提高了约2倍。通过使用帧间滤波，注射整合素靶向微泡后肿瘤对比比非靶向对照微泡高24.8±1.6 dB，而缺乏目标整合素区域的回波与肿瘤回波相比被抑制了26.2±2.1 dB。由于实时三维（3D）分子成像能更全面地显示受体分布，我们生成了肿瘤的3D图像以估计其体积，这些测量结果与预期肿瘤大小相关性良好。我们得出结论，TLRH与帧间滤波相结合是一种可行的3D靶向超声成像方法，比当前的多脉冲策略更快。
