New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

Marco Palombo (1) , Clémence Ligneul (1) , Chloé Najac (1) , Juliette Le Douce (1) , Julien Flament (1, 2) , Carole Escartin (1) , Philippe Hantraye (1, 2) , Emmanuel Brouillet (1) , Gilles Bonvento (1) , Julien Valette (1)

1 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
2 INSERM - Institut National de la Santé et de la Recherche Médicale

The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cell-specific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histol-ogy (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas den-dritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively. cell morphology | noninvasive histology | diffusion-weighted NMR spectroscopy | numerical simulations | metabolites T he brain is one of the most complex organs, and it has defined an inexhaustible field of research over the last centuries. Unfortunately , brain's complexity is paralleled by the difficulty in examining it noninvasively.

Keywords: cell morphology; noninvasive histology; diffusion-weighted NMR; spectroscopy; numerical simulations; metabolites

Domains: Imaging

Marco Palombo, Clémence Ligneul, Chloé Najac, Juliette Le Douce, Julien Flament, et al.. New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113 (24), pp.6671-6676. ⟨10.1073/pnas.1504327113⟩. ⟨cea-02155309⟩