Imaging acquisition, preprocessing and analysis framework to integrate fetal T2w and DWI imaging for the investigation of microstructure on the fetal brain surface.

(a) Mean sulcal depth values across the surface at biweekly intervals and whole brain sulcal depth for each subject, plotted against GA in weeks (b) Illustration of the cortical plate (grey) and subplate (purple) compartments, separated by the surface boundary (white), and diagram of cytoarchitecture of fetal layers (adapted from Kostović and Judaš, 2015) (c) Biweekly mean CP tissue fraction and (d) fluid fraction for each surface vertex, projected to the surface and charted against GA (e) Biweekly mean SP tissue fraction and (f) fluid fraction for each surface vertex, projected to the surface and plotted against GA (grey = left, black = right), best fit with a 2nd order polynomial curve.

Within-subject tissue fraction vs. sulcal depth neighbourhood analysis (a) Schematic to demonstrate the neighbourhood concept for local patch analysis on the surface, and the degrees of separation between the central vertex and surrounding neighbours. (b) Example of 27 GW subject, and how ‘r’ value is derived, correlating sulcal depth and tissue fraction in a local patch in the central sulcus area (c) Example of neighbourhood in central sulcus at 35 GW. (d,e) Example subjects at whole brain level, with r values projected to the surface, colourbar represents strength of correlation (magnitude of r Pearson value). (f) Mean Pearson r for subjects grouped into biweekly bins, representing correlation between tissue fraction and sulcal depth in CP and SP across the whole brain (only significant values after FDR correction are shown, q = 0.05).

Age-mismatched analysis highlights brain regions where changes in microstructure precede the formation of sulcal folds, in the (a) SP and (b) CP. Red boxes are whole-brain correlation coefficient values for the relationship between sulcal depth at 35 GW and biweekly mean tissue fraction at 25, 27 and 29 GW. Arrows indicate areas of strong change between age matched and mismatched analysis, including the inferior frontal sulcus, superior temporal sulcus, post-central sulcus and insula. (c) Close-up, of correlation coefficient describing relationship between tissue fraction at 25 – 30 GW and sulcal depth at 35 GW in specific primary sulci, including (i) Central Sulcus, (ii) Inferior Frontal Sulcus (iii) Post central sulcus and (iv) Superior temporal sulcus.

The inverse relationship between tissue fraction and sulcal depth recapitulates adult cytoarchitectural organisation in utero.