Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation

Description

Biological sex influences prevalence of developmental disorders through sex hormones and sex chromosomes. However, our understanding of their impacts in neurodevelopment and response to injury remains limited. In this project, we use high resolution magnetic resonance imaging (MRI) to investigate the four core genotype mouse model (FCG) that separates the influences of sex hormones and sex chromosomes during normal brain development and after cranial radiation therapy. 

Sex differences are attributed to either sex hormones or sex chromosomes. This can be distinguished by the FCG model which decouples the sex determining region (SRY) from the Y chromosome by moving SRY onto an autosome. This gives us four core sex genotypes: XX NULL, XY NULL, XX SRY, and XY SRY.

This dataset represents the most comprehensive mouse brain imaging study employing the FCG model to date with 5 timepoints (P14, P23, P42, P63, P98), Ccl2 wildtype (+/+) and knockouts (-/-), irradiation (7Gy) and sham (0Gy) mice. All in all, a total of 1071 images! The results presented here is published in PNAS.

In vivo MRI scans were obtained using a 7-T MRI scanner (Bruker BioSpin, Ettlingen, Germany) equipped with four cryocoils for simultaneous imaging of four mice. The scans were performed with the following settings: T1-weighted, 3D-gradient echo sequence, 75μm isotropic resolution, TR=26ms, TE=8.25ms, flip angle=26°, field of view=25×22×22mm, and matrix size=334×294×294.

All structural MR images are stored in images.tar.gz. Images were segmented and registered using an automated pipeline which are stored in labels.tar.gz. The consensus average and labels are final_average.mnc and final_labels.mnc, respectively. Extracted structure volumes alongside the metadata are included in df_micevolumes.csv. Structural MRIs are in MINC format and the readme.txt provides further information on this dataset. 

The authors express their sincere gratitude for the research funding recieved from the Canadian Institutes of Health Research (158622, 168037) and the Ontario Institute for Cancer Research (IA-024) with funding from the Government of Ontario and Restracomp from the SIckKids Research Training Centre.

Publication: https://www.pnas.org/doi/10.1073/pnas.2404042121

Code/Software 

MINC
https://www.bic.mni.mcgill.ca/ServicesSoftware/MINC

RMINC
https://github.com/Mouse-Imaging-Centre/RMINC

PydPiper
https://github.com/Mouse-Imaging-Centre/pydpiper/tree/v2.0.19.1