Tracking the in vivo spatio-temporal patterns of neovascularization via NIR-II fluorescence imaging
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Tracking the in vivo spatio-temporal patterns of neovascularization via NIR-II fluorescence imaging Mo Chen§, Sijia Feng§, Yimeng Yang, Yunxia Li, Jian Zhang, Shiyi Chen (), and Jun Chen () Institute of Sports Medicine of Fudan University, Department of Orthopaedic Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200041, China § Mo Chen and Sijia Feng contributed equally to this work. © Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 Received: 8 May 2020 / Revised: 9 July 2020 / Accepted: 10 July 2020
ABSTRACT The in vivo spatio-temporal patterns of neovascularization are still poorly understood because it is limited to multi-scale techniques from the cellular level to living animal level. Owing to deep tissue-penetration and zero autofluorescence background, the second near-infrared (NIR-II, 1,000–1,700 nm) fluorescence imaging recently shows promise in breaking through this dilemma by dynamically tracking the pathophysiological process of neovascularization in vivo. Here, NIR-II fluorescence imaging was recruited for monitoring blood vessels in order to visualize the vascular injury and quantitively assess neovascularization in mouse models of acute skeleton muscle contusion and hindlimb ischemia. The temporal analysis of real-time NIR-II fluorescence intensity demonstrated that the blood flow perfusion of ischemia area was able to rapidly restore to 96% of pre-ischemic state within one week. Moreover, the spatial analysis revealed that the lower and outer quadrants of ischemia area in the mouse model of hindlimb ischemia always had relatively high blood flow perfusion compared with other quadrants during three weeks post-ischemia, and even exceeded pre-ischemic quantity at 21 days post-ischemia. In conclusion, this in vivo imaging technique has significant potential utility for studying the spatio-temporal patterns of neovascularization in vivo.
KEYWORDS bioimaging, second near-infrared (NIR-II) fluorescence, nanoprobes, spatio-temporal, neovascularization
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Introduction
Neovascularization is always accompanied by vascular or tissue injury, as it is crucial for adaptation and regeneration in response to pathological conditions [1]. Nowadays, the in vivo monitoring neovascularization based on temporal and spatial patterns is neglected, while it has significant implications for investigating the internal mechanism of neovascularization. The temporal distribution of neovascularization reflects the overall restoration of blood flow perfusion in the diseased tissue [2, 3]. And the spatial distribution of neovascularization is informative to understand the vascular biology in growth and development, including growth tendency and direction. Furthermore, in vivo tracking neovascularization deepens understanding the underlying mechanism of neovascularization compared to ex vivo and in vitro. At present, in vivo tracking of tissues or cells mainly depends on imaging techniques, such as routine clinical imaging techniques-computed tomography (CT), magnetic resona
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