Shedding Light on Regional Lung Structure & Function with Synchrotron Radiation

• Sam BAYAT (Univerisité de Grenoble Alpes)

Room: 985 0323 0648 Elucidating the 3D structure and real-time function of the lung at small length scales in vivo, is one of the most challenging applications of synchrotron radiation in biomedical imaging. Dynamic measurements allowing the study of regional lung function, with methods using synchrotron radiation such as K-edge subtraction imaging are crucial for better understanding of phenomena such as gas transport and exchange, adverse effects of mechanical ventilation on the lung and strategies to prevent them, aerosol transport and deposition, among other applications. On the other hand, the coherence of synchrotron beams allows phase-contrast imaging of the poorly radiation-absorbing lung tissue, allowing enhancement of structural details. Real-time imaging of lung function is highly challenging at small length-scales. There is currently a trade-off between spatial and temporal resolutions, and both are difficult to achieve simultaneously. In vivo synchrotron radiation imaging also faces limitations due to radiation dose. Improvements in the available detector technology, allowing for significant gains in spatial resolution, efficiency, dynamic range, energy resolution as well as temporal resolution will be crucial for overcoming these limitations. Examples of in vivo synchrotron imaging in investigating models of lung diseases will be discussed.

X-Ray Phase Contrast Imaging for Biomedicine

• Emmanuel Brun (Inserm UA07)

Room: 985 0323 0648 Since the seminal work of Roentgen, conventional X-ray imaging is based on the same physical phenomenon: the absorption of light by the tissues. The refraction index of light element materials can be a thousand times greater than its counterpart the absorption factor for the wavelength in radiology. In this talk we will explore the interest of using refraction of tissues at the organ and the cell scale.

High-Resolution Quantitative Label-Free Microscopy: Probing the Nano-Bio-World

• Julio Cesar da Silva (Institut Néel CNRS)

Room: 985 0323 0648 Today, we know how the nano-structures and the process happening at the nanometric scale affect the macroscopic behaviour of biological systems. Therefore, we need to be able to image the biological sample down to the nanometric length scale, which is a big challenge. In some cases, we can tag, stain or label the system of interest, but in other case, this is not possible and label-free imaging is necessary. In this talk, I will give a brief overview of how to carry out X-ray nanoimaging of biological systems.

Unveiling the Chemical Landscape of Cells Using Synchrotron X-Ray Nano-Probe

• Sylvain Bohic (Inserm UA07)

Room: 985 0323 0648 Several essential metal ions participate in the control of numerous metabolic and signaling pathways, but their rich coordination chemistry and redox properties confer them a propensity to randomly coordinate and catalytically react inside the cell with protein sites other than those tailored for that purpose. A number of sophisticated networks of trafficking pathways are available to tightly regulate their uptake, intracellular transport and compartmentalization, and to avoid their toxic side effects. Cutting-edge technique providing quantitative imaging for detailed study of elemental homeostasis or the intracellular distribution of metal-based drugs at biologically relevant concentration in a label-free fashion is highly desirable. The synchrotron X-ray fluorescence (XRF) nanoprobe as developed today provide the required sensitivity and spatial resolution to elucidating the 2D and 3D distribution, concentration of elements particularly metals inside entire cells at the organelle level. The new state-of-the-art Nano-Imaging beamline ID16A-NI at ESRF offers unique capabilities for X-ray imaging at nanometer scale at high energies (~30nm at 17kev) [1]. It is particularly well suited for the investigation of biological samples at high spatial resolution, e.g. combined hard X-ray phase imaging and XRF detection and quantification of trace elements [2]. A critical issue is to best preserve the structural and chemical integrity of the cells. As it has been demonstrated in electron microscopy or recently for synchrotron 3D-XRF [3], a cryogenic workflow including cryo-immobilization of the cell and cryotransfer to a cryo-scanning stage allow an optimal elemental preservation at subcellular level as close as possible to their native state. In this work, we will illustrate the unique capabilities of this techniques to provide insight in the intracellular targeting of new organometallic drugs, i.e osmocifen [3] on breast cancer cells but also on the fate of metal-based nanoparticles on cancer cells. We will try to underline the importance of correlative sub-cellular imaging for better understanding of the role of metals in cells. References: [1] J. C. Da Silva et al, Optica 2017, 4, 492; [2] Bohic S. et al., Journal of Structural Biology, 2012, 177, 248; [3] Fus F. et al, Angwendte Chemie. 2019, doi: 10.1002/anie.201812336