Advanced methods of blockwise diffusion imaging for studying fetal cerebral development at the mesoscopic scale

Keywords: neurodevelopment, diffusion MRI, ultra high field MRI, fetus, mesoscopic imaging

Profile and skills required

• Master 2 or engineering degree
• Strong background in image analysis and/or applied mathematics
• Programming: Python, C++
• Interest in developmental neuroscience
• Interest in experimental work, notably on anatomical samples
• Fluent English, written and spoken

Project description

The second half of pregnancy is an extremely rich period in terms of brain development, during which key processes such as neurogenesis, neuronal migration, and axonal growth take place; transient structures form and disappear, while brain volume increases more than tenfold. A blockwise ex-vivo imaging technique recently developed in NeuroSpin allows us to take a new look on developing brain tissues, leveraging ultra-high-field MRI at 11.7 teslas to acquire unprecedented whole-brain images at mesoscopic resolution (100 to 200 µm 3D isotropic) . The acquired data is highly multiparametric, including quantitative T1, T2, and T2* mapping, as well as high angular resolution, multi-shell diffusion-weighted imaging (b = 1500, 4500, 8000 s/mm² with 25, 60, and 90 directions respectively) at 200 µm isotropic resolution.

In order to reach such a high level of detail, a small-bore scanner is used (5 cm usable diameter) over extended scanning times (150 hours per field of view). Brains older than about 20 gestational weeks are too large, and are sectioned into blocks whose size is compatible with the scanner. The resulting blockwise images are registered using a dedicated semi-automatic protocol, and fused to reconstruct a set of whole-brain images. While this protocol has allowed us to obtain good-quality images on several fetal brain specimens (3 published, 3 other brains in progress as of the end of 2025), the diffusion imaging data remains to be fully analyzed: indeed, the blockwise nature of the acquisitions poses unique challenges, notably due to the discontinuity at the boundary between blocks, but also to non-linear image deformations and non-linearity of the magnetic field gradients.

The PhD candidate will be hosted in the inDEV team (imaging neurodevelopmental phenotypes) in close collaboration (co-supervision) with the Ginkgo team, which has leading expertise in diffusion imaging methods and has pioneered the blockwise acquisition technique in an adult brain known as Chenonceau. The PhD work lies at the interface between imaging, algorithmics, and developmental neuroscience: it will include developing and benchmarking new methods for processing this blockwise diffusion MRI to obtain high-quality tractography and fit diffusion microstructural models. It will also include an experimental part, where the PhD candidate will take part in the acquisition and reconstruction of new brains, both typical specimens and pathological ones with agenesis of the corpus callosum. Finally, the candidate will explore neuroscientific outcomes of this unprecedented dataset, which has exceptional potential to describe processes such as the development of subcortical pathways and associative white matter fibre tracts, and to become the first atlas of the developing fetal brain with fibre architecture at the mesoscopic scale.

References

1. Arcamone et al. Multimodal imaging of human fetal brain development at the mesoscopic scale using 11.7 T ex vivo MRI. bioRxiv preprint (2025). Under review.
2. Bayer & Altman. The Human Brain During the Third Trimester. (CRC Press, 2003).
3. Wilson et al. Development of human white matter pathways in utero over the second and third trimester. PNAS 118 (2021).
4. Brandstaetter et al. Differential microstructural development within sensorimotor cortical regions: A diffusion MRI study in preterm and full-term infants. Developmental Cognitive Neuroscience 75 (2025).
5. Mitra et al. A three-dimensional histological cell atlas of the developing human brain. Preprint (2025).
6. Vasung et al. Ex vivo fetal brain MRI: Recent advances, challenges, and future directions. NeuroImage 195, 23–37 (2019).
7. Beaujoin, J. et al. CHENONCEAU: towards a novel mesoscopic (100/200µm) post-mortem human brain MRI atlas at 11.7T. in OHBM (Rome, Italy, 2019).
8. Arcamone et al. Multimodal imaging of human fetal brain development at the mesoscopic scale using 11.7 T ex vivo MRI (v1). EBRAINS (2025). Dataset.
9. Zhang, H. et al. NODDI: Practical in vivo neurite orientation dispersion and density imaging of the human brain. NeuroImage 61, 1000–1016 (2012).
10. Jeurissen, B. et al. Multi-tissue constrained spherical deconvolution for improved analysis of multi-shell diffusion MRI data. NeuroImage 103, 411–426 (2014).

Further information

https://app.doctorat.gouv.fr/proposition?id=9130

https://adum.fr/as/ed/voirproposition.pl?site=adumR&matricule_prop=71654

How to apply

Send CV and cover letter to yann.leprince@cea.fr