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Cryo-X-ray phase contrast imaging for 3D structural and molecular analysis of frozen biopsy samples

Nature Reviews Cardiology (2024)Cite this article

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Cardiac biopsies are an important tool for advancing our understanding of myocardial diseases, particularly cardiomyopathy. These biopsies involve the careful removal of small samples of heart tissue, providing a valuable source of archival material for studying the disease process and identifying potential therapeutic targets. However, preserving the molecular integrity of biopsy samples is crucial to ensure accurate analyses. In surgical settings, biopsy samples are typically snap frozen (which involves rapidly freezing the tissue by submerging it in liquid nitrogen) to prevent the degradation of DNA, RNA and proteins.

The analysis of biopsy samples can be challenging owing to the limitations of current techniques. Traditional methods require careful tissue selection, orientation, processing and sectioning, which can all affect the structural and molecular integrity of the tissue, thereby complicating data interpretation. To address these challenges, synchrotron-based cryo-X-ray phase contrast imaging (cryo-X-PCI) has been developed. This tool exploits the properties of synchrotron radiation to image frozen tissues at high resolution and contrast without the need for tissue sectioning or staining.

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Acknowledgements

K.Y.C.L. thanks the British Heart Foundation for funding the work on cryo-X-PCI (BHF FS/4yPhD/F/20/34134) and acknowledges her PhD supervisory team, Andrew C. Cook and Petros Syrris (UCL Institute of Cardiovascular Science, London, UK) and Hector Dejea (European Synchrotron Radiation Facility, Grenoble, France), for their support and discussions. She also thanks Vishwanie Budhram-Mahadeo (UCL Institute of Cardiovascular Science, London, UK) for providing wild-type C57BL/6 mice for the study (project licence number PB12FFA7E), Thomas Treibel (St Bartholomew’s Hospital, London, UK) for providing biopsy samples from patients with aortic stenosis, and the Paul Scherrer Institut, Villigen, Switzerland, for synchrotron radiation beamtime at the TOMCAT beamline X02DA of the Swiss Light Source.

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  1. Centre for Cardiac Morphology and Structural Heart Disease, Institute of Cardiovascular Science, London, UK

    Kan Yan Chloe Li

  2. Paul Scherrer Institute, Villigen, Switzerland

    Anne Bonnin

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  1. Kan Yan Chloe Li
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  2. Anne Bonnin
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Correspondence to Kan Yan Chloe Li.

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The authors declare no competing interests.

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Li, K.Y.C., Bonnin, A. Cryo-X-ray phase contrast imaging for 3D structural and molecular analysis of frozen biopsy samples. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-024-01084-0

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  • DOI: https://doi.org/10.1038/s41569-024-01084-0

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