Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography.
Claire L WalshPaul TfforeauW L WagnerD J JafreeAlexandre BellierChristopher WerleinM P KühnelE BollerSimon Walker-SamuelJ L RobertusDavid A LongJ JacobS MarussiE BrownNatalie Aroha HolroydD D JonigkMaximilian AckermannPeter David LeePublished in: Nature methods (2021)
Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)'s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).
Keyphrases
- endothelial cells
- coronavirus disease
- high resolution
- computed tomography
- induced pluripotent stem cells
- dual energy
- contrast enhanced
- pluripotent stem cells
- magnetic resonance
- magnetic resonance imaging
- sars cov
- positron emission tomography
- induced apoptosis
- palliative care
- risk assessment
- endoplasmic reticulum stress
- machine learning
- signaling pathway
- functional connectivity
- mass spectrometry
- oxidative stress
- subarachnoid hemorrhage