CE37 - Neurosciences intégratives et cognitives

Premature Human Connectome Patterns: mapping the fetal brain development using extreme field MRI – p-HCP

Submission summary

The incidence of preterm birth and the survival rate of preterm infants are increasing in developed countries. Injury to the perinatal brain is a leading cause of death and disability. Preterm brain encephalopathy is a complex association of primary destructive disease and secondary maturational disturbance. Clinicians and radiologists still lack objective, standardized and validated data to accurately determine the neurodevelopmental prognosis of a given preterm neonate and to optimize his/her management and follow-up. Magnetic resonance imaging provides the best non-invasive, "in vivo" assessment of brain development, extent injury and the anatomical structures involved in neurodevelopmental disorders.

We aim at the development of a new longitudinal description of the foetal brain at unprecedented precision, between 16 and 40 gestational weeks (GW) and at the further characterization of clinically relevant MRI lesions of the premature brain (born 24-36 GW) using co-registered 3T, 11.7T MRI and histological investigations. Our proposal is organized in 4 steps corresponding to specific objectives:
[Objective 1]: Acquisition of a mesoscopic scale extreme field 11.7T anatomical, diffusion, relaxometric MRI database of ex vivo foetal /neonates brains born between 16 and 40 GW, including apparently normal and pathological states, and construction of individual quantitative mappings.
[Objective 2]: Study the neuropathologic substrates of normal and abnormal signals observed on in situ post mortem 3T and ex vivo 11.7 MRI of premature brains, advanced registration to corresponding MRI scans, and correlation study between histological/immunohistological and quantitative MRI imaging markers.
[Objective 3]: Construction of a novel longitudinal post-mortem multimodal MRI and 3D histological atlas of control brains (16-40 GW) and preterm neonates brains born beyond 24 GW using advanced registration techniques to serve as a template to better decipher the microstructure alterations of WM lesions in preterm neonates.
[Objective 4]: Characterization of microstructure alterations within white matter lesions in preterm infants by comparison with the typical brain atlas and histological validation.

This project is a “collaborative research project”, which puts together complementary and synergic expertise of the 3 partners. p-HCP represents a unique opportunity to provide a 3D histology, 3T and 11.7 MRI post mortem atlas, describing the developing human connectome brain of foetal/preterm individuals with and without lesions, to strengthen and ameliorate the performance of brain imaging in the diagnosis of neurological diseases of preterm infants and to open the way to microscopic MRI diagnosis. This study is a fundamental step for the understanding of histological substrate of signal abnormalities observed (or not) on MRI, and an indispensable source of information that can help physicians and neuroscientists in the diagnostic, management, follow up, elaboration of prognosis factors, development of imaging biomarkers, pathophysiological and translational research and design of specific neuroprotective strategies.

Project coordination

Homa ADLE-BIASSETTE (Maladies neurodéveloppementales et neurovasculaires = Neurodevelopmental and Neurovascular Disorders)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LIP6 Laboratoire d’Informatique de Paris 6
JOLIOT Institut des sciences du vivant FRÉDÉRIC-JOLIOT
NeuroDider Maladies neurodéveloppementales et neurovasculaires = Neurodevelopmental and Neurovascular Disorders

Help of the ANR 587,098 euros
Beginning and duration of the scientific project: December 2021 - 48 Months

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