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Annonce

11 mars 2019

Virtual histology of amyloid-β plaques in Alzheimer’s disease using X-ray phase contrast-computed tomography


Catégorie : Doctorant


Virtual histology of amyloid-β plaques in Alzheimer’s disease using X-ray phase
contrast-computed tomography
Disciplines: Biophysics, Neuroimaging, Image processing
Laboratory: Lyon Neuroscience Research Center (dir. O. Bertrand), team BIORAN –
Radiopharmaceutical and Neurochemical Biomarkers
Doctoral school: Interdisciplinary Doctoral program in health-sciences (EDISS) - ED 205

 

Description
Scientific background and rationale. In Alzheimer’s disease (AD), the peptide amyloid-β (Aβ) is
the main component of extracellular fibrillar plaques that develop years before the appearance of
cognitive symptoms. Synchrotron-radiation X-ray phase-contrast tomography offers a great
opportunity to perform high-resolution virtual histology on ex-vivo, labelled-free brain tissue for
the study of neurological pathologies. 1 Previous propagation-based Phase Contrast Imaging (PCI)
experiments, performed at the European Synchrotron Radiation Facility (Grenoble, France), on
various animal models of Alzheimer’s disease and tissue from patients, highlighted intriguing
differences in plaque morphology and PCI contrast among species (unpublished observations).
Aim. The first objective is to develop a segmentation and quantification pipeline for Aß plaques
detected by PCI. Full 3D-analysis is expected to provide quantitative parameters hardly available
with standard histology. The second objective of the PhD project is to understand the substrate of
amyloid plaques detection in PCI. Phase shifts induced by fibrillar amyloid itself, but also X-ray
attenuation from metals entrapped in the plaque, could contribute to signal formation.
Description of the project methodology. Transgenic animal models (mouse and rat) are available
through partner laboratories in Europe, and human tissue from sporadic and rare genetic cases
are available from the neuropathology department in Lyon Hospital (Dr David Meyronet). Semi-
automated segmentation of Aß plaques will be developed with machine-learning techniques, and
will provide new metrics for the comparison of plaque morphology among species.
Complementary synchrotron-based experiments will be performed to study both structural and
elemental composition of plaques: 2 on one hand, Fourier Transform Infrared micro-spectroscopy
(FTIR) will allow to measure the content of fibrillar material in individual plaques (secondary
structure of proteins – α-helix/β-sheet, and lipid fraction); on the other hand, X-ray fluorescence
(XRF) will enable the detection of trace metals at the micrometer level.
Expected results. Quantifying 3D morphologies, and understanding the substrate of amyloid
plaque detection are awaited, pivotal milestones in the development of phase contrast imaging in
neuroscience research.
Perspectives. This emergent imaging modality might greatly expand its scope in the near future
by being adapted to standard laboratory CT scanners. Preliminary tests may be conducted on
conventional x-ray source (collaboration with E. Brun, Grenoble, France).
Skills required: motived, autonomous, and well-organized; knowledge or previous experience in
imaging techniques; skills in image processing would be a plus.
Bibliography:
[1] Albers J, et al. Mol Imaging Biol. 2018;20(5):732-741. [2] Miller, L. M., et al. J Struct Biol. 2006;155(1), 30-37.
Key-words: Alzheimer’s disease; amyloid-β; phase-contrast imaging; synchrotron techniques

Contact: Fabien Chauveau (chauveau[at]cermep.fr)
Application should include: CV, application letter, Names and addresses of two references.
The application file should be sent before May 31, 2019 to: chauveau[at]cermep.fr
The open competitive recruitment process is in two steps:
1. Internal laboratory procedure. 2. Interdisciplinary jury of EDISS

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