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Regenerative therapies follow-up

Stroke is the leading cause of long-term disability, resulting in an increasing need for a reliable and reproducible brain regeneration technique. Several types of regenerative therapies are currently being evaluated, the introduction of stem cells through intracerebral route proving to be associated with the best recovery to date compared to other administration routes.

It is thus essential to develop imaging modalities that allow the monitoring of the administered cells in order to follow their fate in a non-invasive manner. Labeling the injected cells using gold nanoparticles (AuNPs) allows monitoring the cells with CT-based imaging techniques.

Novel experimental CT techniques, namely Phase Contrast [1] and Spectral Imaging [2], that have been introduced in synchrotrons in the past years and recently translated to the clinics[3], [4], may help to overcome those limitations. While they were developed in parallel, the aim of this project is to combine the two approaches for improved segmentation of labeled-cells with a focus on small animal follow-up with a model of focal cerebral injury mimicking stroke infarct and an osteoarthritis model. 

This project, named BREAKTHRU, is funded by the French Research National Agency (ANR-18-CE19-003-01). 

The figure below shows preliminary results

stroke3d.jpg
Segmentation of the Au Np labeled cells

References

  1. R. Ashton, J. L. West, and C. T. Badea, “In vivo small animal micro-CT using nanoparticle contrast agents,” Front. Pharmacol., vol. 6, p. 256, Nov. 2015, doi: 10.3389/fphar.2015.00256.
  2. A. Bravin, P. Coan, and P. Suortti, “X-ray phase-contrast imaging: from pre-clinical applications towards clinics.,” Phys. Med. Biol., vol. 58, no. 1, pp. R1–R35, Jan. 2013, doi: 10.1088/0031-9155/58/1/R1.
  3. W. Thomlinson, H. Elleaume, L. Porra, and P. Suortti, “K-edge subtraction synchrotron X-ray imaging in bio-medical research,” Phys. Medica, vol. 49, pp. 58–76, May 2018, doi: 10.1016/j.ejmp.2018.04.389.
  4. K. Willer et al., “X-ray dark-field imaging of the human lung—A feasibility study on a deceased body,” PLoS One, vol. 13, no. 9, p. e0204565, Sep. 2018, doi: 10.1371/journal.pone.0204565.

BREAKTHRU project

People Involved:
Helene Elleaume
Marlene Wiart (Carmen)
Emmanuel Brun
Clément Tavakoli

Partners:
Carmen
Institute for Regenerative Medicine & Biotherapy
Grenoble Institute of Neurosciences 
CERMAV 
 UPenn

Submitted on February 19, 2020

Updated on February 21, 2024