Knight Cardiovascular Institute, Portland, Oregon.
Philips Ultrasound, Bothell, Washington; and Philips Research, Cambridge, Massachusetts.
JACC Cardiovasc Imaging. 2020 Mar;13(3):641-651. doi: 10.1016/j.jcmg.2019.06.012. Epub 2019 Aug 14.
The authors investigated ideal acoustic conditions on a clinical scanner custom-programmed for ultrasound (US) cavitation-mediated flow augmentation in preclinical models. We then applied these conditions in a first-in-human study to test the hypothesis that contrast US can increase limb perfusion in normal subjects and patients with peripheral artery disease (PAD).
US-induced cavitation of microbubble contrast agents augments tissue perfusion by convective shear and secondary purinergic signaling that mediates release of endogenous vasodilators.
In mice, unilateral exposure of the proximal hindlimb to therapeutic US (1.3 MHz, mechanical index 1.3) was performed for 10 min after intravenous injection of lipid microbubbles. US varied according to line density (17, 37, 65 lines) and pulse duration. Microvascular perfusion was evaluated by US perfusion imaging, and in vivo adenosine triphosphate (ATP) release was assessed using in vivo optical imaging. Optimal parameters were then used in healthy volunteers and patients with PAD where calf US alone or in combination with intravenous microbubble contrast infusion was performed for 10 min.
In mice, flow was augmented in the US-exposed limb for all acoustic conditions. Only at the lowest line density was there a stepwise increase in perfusion for longer (40-cycle) versus shorter (5-cycle) pulse duration. For higher line densities, blood flow consistently increased by 3-fold to 4-fold in the US-exposed limb irrespective of pulse duration. High line density and long pulse duration resulted in the greatest release of ATP in the cavitation zone. Application of these optimized conditions in humans together with intravenous contrast increased calf muscle blood flow by >2-fold in both healthy subjects and patients with PAD, whereas US alone had no effect.
US of microbubbles when using optimized acoustic environments can increase perfusion in limb skeletal muscle, raising the possibility of a therapy for patients with PAD. (Augmentation of Limb Perfusion With Contrast Ultrasound; NCT03195556).
作者研究了为临床超声（US）空化介导的血流增强而定制的扫描仪上的理想声学条件。然后，我们将这些条件应用于首例人体研究中，以验证这样一个假设，即对比超声可以增加正常受试者和外周动脉疾病（PAD）患者的肢体灌注。
超声诱导微泡造影剂空化通过对流剪切和继发性嘌呤能信号传导来增强组织灌注，后者介导内源性血管扩张剂的释放。
在小鼠中，在静脉注射脂质微泡后，对单侧后肢进行 10 分钟的治疗性超声（1.3MHz，机械指数 1.3）照射。超声根据线密度（17、37、65 线）和脉冲持续时间而变化。使用超声灌注成像评估微血管灌注，使用体内光学成像评估体内三磷酸腺苷（ATP）释放。然后，在健康志愿者和 PAD 患者中使用最佳参数，单独或静脉内微泡造影剂输注 10 分钟。
在小鼠中，所有声学条件下，超声照射肢体的血流均增加。只有在线密度最低的情况下，较长（40 个周期）与较短（5 个周期）脉冲持续时间相比，灌注才有逐步增加。对于更高的线密度，超声照射肢体的血流始终增加 3 到 4 倍，而与脉冲持续时间无关。高线密度和长脉冲持续时间导致空化区中 ATP 的释放最大。在人体中应用这些优化条件以及静脉内对比剂可使健康受试者和 PAD 患者的小腿肌肉血流增加 2 倍以上，而单独使用 US 则没有效果。
在使用优化的声学环境时，超声微泡可以增加肢体骨骼肌的灌注，为 PAD 患者的治疗提供了可能性。（对比超声增强肢体灌注；NCT03195556）。
