Biological cells and tissues studied by holographic X-ray microscopy and tomography

Jan-David Nicolas

X-rays deeply penetrate matter and thus provide information about the functional (interior) architecture of complex samples, from biological tissues and cells to novel composite materials. However, this potential of hard x-rays in view of penetration power, high spatial resolution, quantitative contrast, and compatibility with environmental conditions has to date not been fully developed, mainly due to significant challenges in X-ray optics. With the advent of highly brilliant radiation, coherent focusing, and lensless diffractive imaging this situation has changed. We show how hard X-rays focused to nanometer spot sizes can be used for scanning as well as for full field holographic X-ray imaging of biological samples [1]. The central challenge of inverting the coherent diffraction pattern will be discussed for holographic techniques [2] and ptychography [3,4].

By scanning the sample through the focused X-ray beam and recording diffraction patterns in each scan point, structural parameters can be mapped throughout the cell or histological section [5], yielding a 'diffraction contrast' image that can show how nanometer-sized structures can vary within the tissue. As an example, we address the sarcomeric organization in heart muscle cells (cardiomyocytes) [6,7], and show how the sarcomere organization evolves and differs between different cell types and maturation states. As a multi-scale approach, we then discuss sarcomeric structure in heart tissue sections [8], and then finally present phase contrast tomography reconstructions of an entire mouse heart. A similar multi-scale approach is outlined for the case of neuronal tissue [9].

[1] Bartels et al., Phys. Rev. Lett. (2015), 114, 048103
[2] Krenkel et al., Acta Crystallogr. A (2017), 73, 282-292
[3] Giewekemeyer et al., PNAS (2010), 107, 529-534
[4] Wilke et al., Optics Express (2012), 20, 19232-19254
[5] Carboni & Nicolas et al., Biomed. Opt. Express (2017), 8, 4331–4347
[6] Bernhardt et al., New J. Phys. (2017), 19, 013012
[7] Nicolas et al., J. Appl. Crystallogr. (2017), 50, 612–620
[8] Nicolas et al., J. Synchrotron Rad. (2017), 24, 1163-1172
[9] Töpperwien et al., PNAS (2018), 115, 6940-6945

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