Harvard Medical School, Massachusetts General Hospital, Cardiovascular Research Center, 185 Cambridge St, Suite 3206, Boston, MA 02114, USA.
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2616-24. doi: 10.1161/ATVBAHA.112.251983. Epub 2012 Sep 20.
Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here, we develop and evaluate 2 integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo.
Murine DVT were created with topical 5% FeCl(3) application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy. Day 4 analyses showed robust relationships among in vivo thrombus macrophages, matrix metalloproteinase activity, and fluorescein isothiocyanate-dextran deposition (r>0.70; P<0.01). In a serial 2-time point study, mice with DVT underwent intravital microscopy at day 4 and day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (P<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography was used and detected macrophages within jugular DVT (P<0.05 versus sham controls).
Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo and can inform the magnitude of thrombus resolution.
体内血栓炎症的评估可为深静脉血栓（DVT）的溶解提供新的见解。在这里，我们开发并评估了 2 种整合的荧光分子-结构成像策略，以定量 DVT 相关炎症和结构，并评估血栓炎症对体内随后 DVT 溶解的影响。
通过局部应用 5%FeCl3 在大腿或颈静脉处建立小鼠 DVT（n=35）。第 3 天，小鼠接受巨噬细胞和基质金属蛋白酶活性荧光成像剂。第 4 天，使用共聚焦荧光活体显微镜对 DVT 炎症和结构进行综合评估。第 4 天的分析表明，体内血栓巨噬细胞、基质金属蛋白酶活性和异硫氰酸荧光素-葡聚糖沉积之间存在很强的相关性（r>0.70；P<0.01）。在一项连续的 2 个时间点研究中，DVT 小鼠在第 4 天和第 6 天进行活体显微镜检查。分析显示第 4 天血栓炎症的强度预测了第 6 天 DVT 溶解的程度（P<0.05）。在第二种方法中，使用非侵入性荧光分子断层扫描-计算机断层扫描检测颈静脉 DVT 中的巨噬细胞（P<0.05 与假对照）。
整合的荧光分子-结构成像表明，DVT 诱导的炎症反应可以在体内进行评估，并可以反映血栓溶解的程度。
