Advanced microscopy to elucidate cardiovascular injury and regeneration: 4D light-sheet imaging

Kyung In Baek; Yichen Ding; Chih-Chiang Chang; Megan Chang; René R Sevag Packard; Jeffrey J Hsu; Peng Fei; Tzung K Hsiai

doi:10.1016/j.pbiomolbio.2018.05.003

Advanced microscopy to elucidate cardiovascular injury and regeneration: 4D light-sheet imaging

Prog Biophys Mol Biol. 2018 Oct:138:105-115. doi: 10.1016/j.pbiomolbio.2018.05.003. Epub 2018 May 9.

Authors

Kyung In Baek¹, Yichen Ding², Chih-Chiang Chang³, Megan Chang⁴, René R Sevag Packard⁵, Jeffrey J Hsu⁶, Peng Fei⁷, Tzung K Hsiai⁸

Affiliations

¹ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
² Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
³ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
⁴ Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
⁵ Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
⁶ Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
⁷ School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address: [email protected].
⁸ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Medical Engineering, California Institute of Technology, Pasadena, CA 91106, USA. Electronic address: [email protected].

Abstract

The advent of 4-dimensional (4D) light-sheet fluorescence microscopy (LSFM) has provided an entry point for rapid image acquisition to uncover real-time cardiovascular structure and function with high axial resolution and minimal photo-bleaching/-toxicity. We hereby review the fundamental principles of our LSFM system to investigate cardiovascular morphogenesis and regeneration after injury. LSFM enables us to reveal the micro-circulation of blood cells in the zebrafish embryo and assess cardiac ventricular remodeling in response to chemotherapy-induced injury using an automated segmentation approach. Next, we review two distinct mechanisms underlying zebrafish vascular regeneration following tail amputation. We elucidate the role of endothelial Notch signaling to restore vascular regeneration after exposure to the redox active ultrafine particles (UFP) in air pollutants. By manipulating the blood viscosity and subsequently, endothelial wall shear stress, we demonstrate the mechanism whereby hemodynamic shear forces impart both mechanical and metabolic effects to modulate vascular regeneration. Overall, the implementation of 4D LSFM allows for the elucidation of mechanisms governing cardiovascular injury and regeneration with high spatiotemporal resolution.

Keywords: Cardiovascular injury; Doxorubicin; Light-sheet fluorescence microscopy; Vascular regeneration.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cardiovascular System / diagnostic imaging*
Cardiovascular System / injuries*
Cardiovascular System / physiopathology
Imaging, Three-Dimensional / methods*
Light*
Regeneration*
Zebrafish

Abstract

Publication types

MeSH terms

Grants and funding