Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:tt77uu
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AIM To study mucosal addressin cellular adhesion molecule-1(MAd CAM-1) and vascular endothelial growth factor(VEGF)-targeted contrast enhanced ultrasound(CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL/6 mice were challenged with 3% dextran sodium-sulfate(DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAd CAM-1-targeted contrast agent was used to detect and quantify MAd CAM-1 expression. Inflammatory driven colorectal azoxymethane(AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis(healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss(r2 = 0.74) and histological damage(r2 = 0.86)(P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAd CAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel(9.6 d B ± 1.6 vs 12.9 d B ± 1.4 vs 18 d B ± 3.33, P < 0.05). Employing the AOM/DSSinduced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa(healthy mucosa, 1.6 d B ± 1.4 vs 42 d, 18.2 d B ± 3.3 vs 84 d, 18.6 d B ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings(VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P < 0.01). CONCLUSION Molecularly targeted CEUS is a highly specific and noninvasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo. AIM To study mucosal addressin cellular adhesion molecule-1 (MAd CAM-1) and vascular endothelial growth factor (VEGF) -targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL / 6 mice were challenged with 3 % dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. MAd CAM-1-targeted contrast agent was used to detect and quantify MAd CAM-1 expression. Inflammatory driven colorectal azoxymethane (AOM) / DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickeni ng that correlated with more progressed and more severe DSS-colitis (healthy mice: 0.3 mm ± 0.03 vs. six days DSS: 0.5 mm ± 0.2 vs. nine days DSS: 0.6 mm ± 0.2, P <0.05). well with clinical parameters such as weight loss (r2 = 0.74) and histological damage (r2 = 0.86) (P <0.01). In acute DSS-induced murine colitis, CEUS targeted against MAd CAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel (9.6 d B ± 1.6 vs. 12.9 d B ± 1.4 vs 18 d B ± 3.33, P <0.05). Employing the AOM / DSS Induced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significant increased echogenicity in tumors as compared to healthy mucosa (healthy mucosa, 1.6 d B ± 1.4 vs 42 d, 18.2 d B ± 3.3 vs 84 d, 18.6 d B ± 4.9, P <0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings ( VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P <0.01). CONCLUSION Molecularly targeted CEUS is a highly specific and noninvasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo.
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