Detection of unstable atheroma plague by contrast ultrasound imaging

粥样斑块的活动取决于持续炎症的严重程度。因此，我们将造影超声应用于炎症成像。我们通过超声发射暂停10分钟后的诊断超声压力获得肾脏的图像，允许在MB注射后白细胞吞噬微泡（MB）。通过从该图像中减去灌注图像，我们从保留的（吞噬的）MB中提取信号。在缺血再灌注模型中，信号分布于髓质，在肾小球肾炎模型中，信号分布于皮质，这与各自模型中白细胞的分布一致。我们将这种成像方法应用于小鼠后肢缺血模型的低灌注炎症组织，更好地模仿动脉粥样硬化斑块。类似的设置提供了代表保留MB的不透明化。因此，使用普通的声压，我们可以通过设计定时来对发炎组织中保留的微泡进行成像。然而，组织学评估 关于我们 其安全性研究显示，在成像24小时后白细胞浸润加重，这是可能导致斑块破裂的不利副作用。为了避免这种副作用，未来需要设计具有先进灵敏度的低声压装置。然而，引起白细胞浸润的副作用可适用于治疗性血管生成，因为白细胞释放血管内皮生长因子和粒细胞集落刺激因子（G-SF）已用于治疗性血管生成。我们将这种方法应用于相同的模型，发现它与300微克G-CSF的预给药组合显著地进一步增强血管生成，所述300微克G-CSF是单药治疗的最小有效剂量。因此，通过使用当前设备的对比超声进行的炎症成像可以评估白细胞浸润或炎症的活性，其确定相应病理的严重性，但炎症加重。然而，这种副作用适用于增强治疗性血管生成，值得在未来的研究中优化。少

Activity of atheroma plaque depends on the severity of ongoing inflammation. Therefore, we applied contrast ultrasound to inflammation imaging. We obtained images of kidneys by diagnostic ultrasound pressure after suspension of ultrasound emission for 10 minutes allowing phagocytosis of microbubbles (MB) by leukocytes following MB injection. By subtracting perfusion image from this image, we extracted signals from retained (phagocytosed) MB. The signal distributed in the medulla in the ischemia reperfusion model and in the cortex in the glomerulonephritis model, which well agreed with the distribution of leukocytes in respective models. We applied this imaging method to mouse hindlimbs ischemia model of hypoperfused-inflamed tissue that better mimics atheroma plaque. The similar settings provided an opacification that represents retained MB. Thus, using ordinary acoustic pressure we can image retained microbubbles in the inflamed tissue by devising timing. However, histological assessm … More ent of its safety revealed that leukocyte infiltration was aggravated after 24 hours of imaging, which was unfavorable side effect potentially causing plaque rupture. In order to avoid this side effect a low-acoustic pressure apparatus with advanced sensitivity needs to be devised in the future. However, the side effect causing leukocyte infiltration could be applicable to therapeutic angiogenesis, because leukocytes release vascular endothelial growth factor and granulocyte colony stimulating factor (G-SF) has been used in therapeutic angiogenesis. We applied this method to the same model and found that it significantly further augmented angiogenesis in combination with pre-administration of 300 microgram G-CSF which was minimum effective dose at monotherapy. Thus, inflammation imaging by contrast ultrasound using current apparatus can evaluate leukocyte infiltration or activity of inflammation which determine the severity of respective pathology, but aggravated inflammation. However, this side effect was applicable to enhancement of therapeutic angiogenesis which would be worth while optimizing in the future study. Less