Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound

作     者：Markus Brückner Jan Heidemann Tobias M Nowacki Friederike Cordes Jorg Stypmann Philipp Lenz Faekah Gohar Andreas Lügering Dominik Bettenworth 

作者机构：Department of Medicine BUniversity Hospital of MünsterD-48149 MünsterGermany Department of GastroenterologyKlinikum Bielefeld MitteAcademic Teaching HospitalUniversity of MünsterD-33604 BielefeldGermany Department of Cardiology and AngiologyUniversity Hospital of MünsterD-48149 MünsterGermany Department of Palliative CareUniversity Hospital of MünsterD-48149 MünsterGermany Department of Paediatric Rheumatology and ImmunologyUniversity Hospital of MünsterD-48149 MünsterGermany Medical Care Center Portal 10D-48155 MünsterGermany 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2017年第23卷第16期

页      面：2899-2911页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100214[医学-肿瘤学] 10[医学] 

主　　题：Colitis Dextran sodium-sulfate AOMDSS Carcinogenesis Ultrasound Contrast-enhanced ultrasound Vascular endothelial growth factor Mucosal addressin cellular adhesion molecule-1 

摘      要：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-posi