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Cell biology

Real-time imaging of dynamic tissues

Nature Methods volume 20, pages 1631–1632 (2023)Cite this article

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A combined modality enables real-time imaging of mouse lungs and spans whole-organ to cellular scales.

Owing to the constant movement of the lungs, intravital imaging in vivo generally requires some means of immobilization or stabilization such as bronchus clamping, halting of respiration (apnea), gluing, vacuum or suction, or inhalational anesthetic1,5. Although all model systems have limitations, these methods often have off-target effects that compromise the homeostasis of the lung. For example, vacuum or suction can result in vascular compression and altered blood flow, and anesthetics such as isoflurane are known to decrease the respiration rate1,5. Banerji, Grifno and colleagues address many of these limitations using surgical removal of the heart–lung block and encapsulation within a prefabricated, transparent and biocompatible ribcage that is designed specifically for the age and strain of mouse in question. Cannulation of the trachea allows for both positive- and negative-pressure ventilation, and cannulation of the pulmonary artery enables perfusion of the vasculature with blood or cell culture media to maintain homeostatic perfusion and hydrostatic pressures4. Indeed, this methodology enables the imaging of lung vasculature in real time via the spread of a vascular label through the pulmonary circulation of healthy lungs, and of lungs in which the pulmonic vasculature is compromised by pneumonia. The true testament of potential of this methodology is the ability to recapitulate physiological and pathophysiological events at the cellular level, as demonstrated using single cancer cells or neutrophils migrating through the pulmonary vasculature. In the case of the latter, the crystal ribcage allows for sufficient temporal and spatial resolution such that individual neutrophil movement through the vascular, interstitial or alveolar compartments can be tracked and quantified.

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Fig. 1: The crystal ribcage.

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Acknowledgements

The Center for Tissue Engineering is funded in part by the Houston Methodist Research Institute Dr. and Mrs. Alan L. Kaplan Centennial Professorship in Cellular Therapeutics and Organ Bioengineering.

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  1. Houston Methodist Research Institute, Houston, TX, USA

    Joan E. Nichols & Sasha R. Azar

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  1. Joan E. Nichols
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  2. Sasha R. Azar
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Correspondence to Joan E. Nichols.

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The authors declare no competing interests.

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Nichols, J.E., Azar, S.R. Real-time imaging of dynamic tissues. Nat Methods 20, 1631–1632 (2023). https://doi.org/10.1038/s41592-023-02047-y

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