From the Cardiovascular Division, Department of Medicine and Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine; and Departments of Biomedical Engineering, and Radiology, University of Virginia, Charlottesville, VA.
Invest Radiol. 2021 Jan;56(1):50-61. doi: 10.1097/RLI.0000000000000733.
Gas-filled microbubbles are currently in clinical use as blood pool contrast agents for ultrasound imaging. The goal of this review is to discuss the trends and issues related to these relatively unusual intravascular materials, which are not small molecules per se, not polymers, not even nanoparticles, but larger micrometer size structures, compressible, flexible, elastic, and deformable. The intent is to connect current research and initial studies from 2 to 3 decades ago, tied to gas exchange between the bubbles and surrounding biological medium, in the following areas of focus: (1) parameters of microbubble movement in relation to vasculature specifics; (2) gas uptake and loss from the bubbles in the vasculature; (3) adhesion of microbubbles to target receptors in the vasculature; and (4) microbubble interaction with the surrounding vessels and tissues during insonation.Microbubbles are generally safe and require orders of magnitude lower material doses than x-ray and magnetic resonance imaging contrast agents. Application of microbubbles will soon extend beyond blood pool contrast and tissue perfusion imaging. Microbubbles can probe molecular and cellular biomarkers of disease by targeted contrast ultrasound imaging. This approach is now in clinical trials, for example, with the aim to detect and delineate tumor nodes in prostate, breast, and ovarian cancer. Imaging of inflammation, ischemia-reperfusion injury, and ischemic memory is also feasible. More importantly, intravascular microbubbles can be used for local deposition of focused ultrasound energy to enhance drug and gene delivery to cells and tissues, across endothelial barrier, especially blood-brain barrier.Overall, microbubble behavior, stability and in vivo lifetime, bioeffects upon the action of ultrasound and resulting enhancement of drug and gene delivery, as well as targeted imaging are critically dependent on the events of gas exchange between the bubbles and surrounding media, as outlined in this review.
目前，充气体微泡作为超声造影的血池对比剂在临床上得到应用。本综述的目的是讨论这些相对不寻常的血管内材料的趋势和问题，这些材料本身不是小分子，不是聚合物，甚至不是纳米颗粒，而是更大的微米级结构，可压缩、灵活、有弹性和可变形。目的是将当前的研究和 20 至 30 年前的初步研究联系起来，这些研究与气泡与周围生物介质之间的气体交换有关，重点关注以下几个方面：（1）微泡在脉管系统中的运动参数与脉管系统的具体情况有关；（2）气泡在脉管系统中气体的吸收和损失；（3）微泡在脉管系统中与靶受体的黏附；（4）在超声照射下微泡与周围血管和组织的相互作用。微泡通常是安全的，所需的材料剂量比 X 射线和磁共振成像对比剂低几个数量级。微泡的应用很快将超出血池对比和组织灌注成像的范围。微泡可以通过靶向对比超声成像来探测疾病的分子和细胞生物标志物。这种方法目前正在临床试验中，例如，旨在检测和描绘前列腺、乳房和卵巢癌中的肿瘤节点。炎症、缺血再灌注损伤和缺血记忆的成像也是可行的。更重要的是，血管内微泡可用于局部沉积聚焦超声能量，以增强药物和基因向细胞和组织的传递，跨越内皮屏障，特别是血脑屏障。总的来说，微泡的行为、稳定性和体内寿命、超声作用下的生物效应以及药物和基因传递的增强，以及靶向成像，都取决于气泡与周围介质之间气体交换的情况，正如本综述中所概述的那样。
