Assessment of Inflammation in an Acute on Chronic Model of Inflammatory Bowel Disease with Ultrasound Molecular Imaging.
Assessment of Inflammation in an Acute on Chronic Model of Inflammatory Bowel Disease with Ultrasound Molecular Imaging.
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DOI：
10.7150/thno.13048
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发表时间：
2015
期刊：
影响因子：
12.4
通讯作者：
Willmann JK
中科院分区：
文献类型：
--
作者：
Machtaler S;Knieling F;Luong R;Tian L;Willmann JK
背景：超声（US）分子成像在临床前炎症性肠病小鼠模型中显示出评估炎症的前景。然而，这些模型在先前正常的结肠上引发急性炎症，与急性加重通常在慢性炎症区域的患者相反。在这项研究中，我们探讨了潜在的双重P-和E-选择素靶向超声成像评估急性炎症小鼠静止的慢性炎症背景。方法：在雄性FVB小鼠中使用3个周期的4%DSS诱导慢性结肠炎。在最后一个DSS周期后2周通过直肠施用1%TNBS开始急性炎症。在静脉内注射靶向P-和E-选择素的微泡后，使用小动物超声系统对处于不同炎症阶段的小鼠进行成像。体内成像结果与离体免疫荧光和组织学相关。结果：急性炎症的诱导导致靶向US信号从5.5 ± 5.1任意单位（a.u.）在第0天至61.0 ± 45.2 a.u.（P < 0.0001）第1天，36.3 ± 33.1 a.u.在第3天，在第5天恢复到与对照相似的水平。免疫荧光显示，与第0天（P-选择素：10.3 ± 5.7%; E-选择素：7.3 ± 7.0%）相比，第1天P-和E-选择素阳性血管的百分比显著增加（P-选择素：21.0 ± 7.1%的血管; P < 0.05; E-选择素：16.4 ±3.7%; P < 0.05）。结论：急性炎症可以在慢性IBD的临床相关鼠模型中使用具有双重P-和E-选择素靶向造影剂的超声分子成像来准确测量。
Background: Ultrasound (US) molecular imaging has shown promise in assessing inflammation in preclinical, murine models of inflammatory bowel disease. These models, however, initiated acute inflammation on previously normal colons, in contrast to patients where acute exacerbations are often in chronically inflamed regions. In this study, we explored the potential of dual P- and E-selectin targeted US imaging for assessing acute inflammation on a murine quiescent chronic inflammatory background. Methods: Chronic colitis was induced using three cycles of 4% DSS in male FVB mice. Acute inflammation was initiated 2 weeks after the final DSS cycle through rectal administration of 1% TNBS. Mice at different stages of inflammation were imaged using a small animal ultrasound system following i.v. injection of microbubbles targeted to P- and E-selectin. In vivo imaging results were correlated with ex vivo immunofluorescence and histology. Results: Induction of acute inflammation resulted in an increase in the targeted US signal from 5.5 ± 5.1 arbitrary units (a.u.) at day 0 to 61.0 ± 45.2 a.u. (P < 0.0001) at day 1, 36.3 ± 33.1 a.u. at day 3, returning to levels similar to control at day 5. Immunofluorescence showed significant increase in the percentage of P- and E-selectin positive vessels at day 1 (P-selectin: 21.0 ± 7.1% of vessels; P < 0.05; E-selectin: 16.4 ±3.7%; P < 0.05) compared to day 0 (P-selectin: 10.3 ± 5.7%; E-selectin: 7.3 ± 7.0%). Conclusions: Acute inflammation can be accurately measured in a clinically relevant murine model of chronic IBD using ultrasound molecular imaging with a dual P- and E- selectin-targeted contrast agent.