In Vivo Imaging of Venous Thrombus and Pulmonary Embolism Using Novel Murine Venous Thromboembolism Model

• Published in: JACC. Basic to translational science Vol. 5; no. 4; pp. 344 - 356
• Main Authors: Okano, Mitsumasa, Hara, Tetsuya, Nishimori, Makoto, Irino, Yasuhiro, Satomi-Kobayashi, Seimi, Shinohara, Masakazu, Toh, Ryuji, Jaffer, Farouc A., Ishida, Tatsuro, Hirata, Ken-ichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2020; Elsevier
• Subjects: 2-photon microscopy; deep vein thrombosis; imaging; PRECLINICAL RESEARCH; pulmonary embolism; venous thromboembolism; FITC; deep vein thrombosis; DVT; PE; 2-photon microscopy; venous thromboembolism; VTE; IVC; ROS; IQR; pulmonary embolism; imaging; DVT, deep venous thrombosis; IVC, inferior vena cava; VTE, venous thromboembolism; PE, pulmonary embolism; FITC, fluorescein isothiocyanate; IQR, interquartile range; ROS, reactive oxygen species
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2020.01.010

[Display omitted] •We established a novel clinically relevant murine DVT model at femoral/saphenous vein induced by flow restriction and light illumination.•Our model newly succeeded in inducing DVT in a valve pocket and enabled spontaneous pulmonary embolism of fibrin-rich thrombus from lower extremity vein, reproducing the clinical VTE scenario.•This model is suitable for motion-free in vivo high-resolution imaging of fibrin-rich DVT development and organization using 2-photon microscopy, enabling the real-time imaging of migration of platelets and leukocytes into the erythrocyte-rich DVT. This work established a new murine venous thromboembolism (VTE) model. This model has multiple novel features representing clinical VTE that include the following: 1) deep venous thrombosis (DVT) was formed and extended in the long axis of femoral/saphenous vein; 2) thrombus was formed in a venous valve pocket; 3) deligation of suture-induced spontaneous pulmonary emboli of fibrin-rich DVT; and 4) cardiac motion-free femoral/saphenous vein allowed high-resolution intravital microscopic imaging of fibrin-rich DVT. This new model requires only commercially available epifluorescence microscopy. Therefore, this model has significant potential for better understanding of VTE pathophysiology.