3d virtual histology with advanced laboratory radiation: from instrumentation and phase retrieval to biomedical application

17:00 – 17:20 BST, 17 July 2024 ‐ 20 mins

Tim Salditt

In order to unravel physiological and pathological mechanisms at the cellular level, structure and processes have to be visualized on a wide range of scales. Imaging at cellular and sub-cellular resolution is the realm of histology. For this purpose, the tissue obtained by surgical intervention or from a post mortem autopsy is cut into thin sections, stained and observed in an optical microscope. In conventional histology, images are obtained only of two-dimensional sections but not of the entire three-dimensional (3D) volume. In order to visualise and to quantify the cytoarchitecture in 3D, even deep in the tissue or organ, we use phase-contrast X-ray computerized tomography , as a tool for quantitative and fully digital 3D virtual histology [1].  We have partially translated  the method using optimized phase retrieval [2,3], from highly coherent synchrotron  to inhouse micro-focus sources. In a multi-scale approach, we  cover a wide range of scales. Since the workflow is non-destructive and fully compatible with standard clinical pathology, we can perform correlative histology studies.

In this talk we discuss instrumentation at µ-focus tomography setups, image formation and advanced phase retrieval of propagation and inline holography data, the respective resolution limits, object constraints, as well as morphometric image analysis. We show how solutions and algorithms of mathematics of inverse problems and machine learning [2-4] help us to meet the challenges of phase retrieval, tomographic reconstruction, segmentation, and more generally image processing of bulky data.  All to the benefit of ambitious imaging projects such as mapping the human brain [4,6] of fighting infectious diseases [6].

References:

[1] T. Salditt, A. Egner and R. D. Luke (Eds.)
Nanoscale Photonic Imaging
Springer Nature (2020), TAP, 134, Open Access Book

[2] L. M. Lohse, A.-L. Robisch, M. Töpperwien, S. Maretzke, M. Krenkel, J. Hagemann and T. Salditt
A phase-retrieval toolbox for X-ray holography and tomography
Journal of Synchrotron Radiation (2020), 27, 3

[3] S. Huhn, L.M. Lohse, J. Lucht, T. Salditt 
Fast algorithms for nonlinear and constrained phase retrieval in near-field X-ray holography based on Tikhonov regularization - arXiv preprint arXiv:2205.01099 (2022)

[4] M. Eckermann, B. Schmitzer, F. van der Meer, J. Franz, O. Hansen, C. Stadelmann and T. Salditt
Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography
Proc. Natl. Acad. Sci. (2021), 118, 48, e2113835118

[5] M. Eckermann, J. Frohn, M. Reichardt, M. Osterhoff, M. Sprung, F. Westermeier, A.Tzankov, C. Werlein, M. Kuehnel, D. Jonigk and T. Salditt 
3d Virtual Patho-Histology of Lung Tissue from Covid-19 Patients based on Phase Contrast X-ray Tomography
eLife (2020), 9:e60408

[6] M. Reichardt, P.M. Jensen, V.A. Dahl, A.B. Dahl, M. Ackermann, H. Shah, F. Länger, C. Werlein, M.P. Kuehnel, D. Jonigk and T. Salditt 
3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography
eLife (2021), 10:e71359
 

Speakers

Tim Salditt

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Tim Salditt

Tim Salditt is professor of experimental physics at the Institute for X-ray Physics of the University of Göttingen. He studied physics in Munich and Grenoble, and received his Ph.D. in 1995 for research in kinetic growth of surfaces and interfaces, which he studied by diffuse X-ray scattering and non-specular reflectivity with Hans Peisl at the University of Munich. He then moved his focus to biophysics, using the newly developed approaches for interface-sensitive scattering to study fluctuations in oriented lipid membranes. In his postdoctoral work with Cyrus Safinya in Santa Barbara, he worked on the structure and interactions of lipid/DNA complexes. Driven by the motivation to study biomolecular assemblies also in the hierarchical and complex functional environment of cells, he developed X-ray waveguide optics for nanoscale holographic imaging and tomography. With his group, he has designed a synchrotron radiation instrument, which they operate at the PETRAIII storage ring, together with DESY. Using a combination of diffraction with micro- and nano-focused beams as well as holographic imaging and tomography, they can now study biomolecular assemblies and biological matter, from the molecular level to biological cells and tissues. Recently, they also got increasingly involved with translating phase contrast tomography from synchrotron to laboratory instrumentation, more amenable for biomedical research groups. They push the limits in X-ray optics, including focusing, wave-front control, coherence, phase retrieval, reconstruction algorithms, information theory and image processing in order to get a maximum of information from a minimum of photons, Tim Salditt has been spokesperson of the collaborative research center Nanoscale Photonic Imaging for 12 years, and is a principle investigator of the DFG Center for Excellence Multi-Scale Bioimaging: from molecular machines to networks of excitable cells. He is a member of the Academy of Science in Göttingen, and of the DESY scientific advisory committee.