超声荧光微泡在脑血管成像中的应用研究

Use of fluorescent ultrasound microbubbles in cerebral vascular imaging

目的采用染料掺杂工程化技术制备超声荧光微泡, 探讨其在脑血管近红外二区荧光成像中的应用效果。方法采用薄膜水化法制备负载吲哚菁绿(ICG)染料的超声荧光微泡ICG-MBs, 比较ICG-MBs和商用SonoVue超声微泡的超声造影性能。采用近红外二区荧光成像技术, 评估小鼠尾静脉注射ICG-MBs后脑血管成像性能, 并对其生物安全性进行评价。结果成功制备了分散均匀、粒径约为1 μm的超声荧光微泡ICG-MBs, 证实该微泡具有普通超声微泡和荧光成像的双重性能。超声造影结果显示, 与同等浓度SonoVue微泡比较, ICG-MBs依然保留微泡的超声造影功能, 且二者超声信号强度相近。在小鼠头皮和颅骨保持完整的情况下, ICG-MBs实现了快速(200 ms)、高空间分辨率(165.1 μm)的脑血管近红外二区荧光成像, 且小鼠各主要器官组织均无明显炎症或损伤。结论超声荧光微泡ICG-MBs具有荧光和超声显影的双重功能, 可实现高灵敏度、高分辨率的小鼠脑血管成像, 为脑血管病的诊断和疗效评价提供了一种新的成像方法。

Objective To prepare fluorescent ultrasonic microbubbles by dye-doping engineering techniques,and to evaluate their use in cerebral vascular imaging with the second near-infrared window(NIR-Ⅱ)fluorescence imaging.Methods Thin film hydration method was used to prepare fluorescent ultrasound microbubbles loaded with indocyanine green(ICG)as a dyeing agent(ICG-MBs).The performance of ICG-MBs in contrast-enhanced ultrasonography was compared with the commercial SonoVue ultrasound microbubbles.Then,NIR-Ⅱfluorescence imaging of cerebral vascularity in mice was performed after caudal vein injection of ICG-MBs,so as to evaluate their biological safety.Results Fluorescent ultrasound microbubbles ICG-MBs with uniform dispersion and particle sizes of about 1µm were successfully prepared,and were confirmed to exhibit dual performance of usual ultrasound microbubbles and fluorescence in the imaging.Contrast-enhanced ultrasonography showed that ICG-MBs retained the ability of contrast-enhancement and led to comparable ultrasound signal intensity as did SonoVue microbubbles at the same concentration.With the mouse scalp and skull intact,use of ICG-MBs achieved in fast(200 ms),high spatial resolution(165.1µm)NIR-II fluorescence imaging of the cerebral vascularity,and did not lead to significant inflammation or damage of major organs or tissues in the mice.Conclusion The fluorescent ultrasound microbubbles ICG-MBs exhibit dual performance of fluorescence and ultrasound contrast-enhanced imaging.The high-sensitivity and high-resolution imaging of cerebral vascularity in mice with ICG-MBs offers a new imaging modality for diagnosis and efficacy evaluation of cerebrovascular disorders.