Detection of unstable atheroma plague by contrast ultrasound imaging
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
Date (from‐to) : 2005 -2006
Author : OHMORI Koji; KOHNO Masakazu; SHINOMIYA Kaori; TAKEUCHI Hiroto
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 assessment 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.