We automatically quantify patterns of normal cortical folding in the developing fetus from in utero MR images (N = 80) overawidegestationalage(GA) range (21.7 to 38.9 weeks). This work on data from healthy subjects represents a first step towards characterising abnormal folding that may be related to pathology, facilitating earlier diagnosis and intervention. The cortical boundary was delineated by automatically segmenting the brain MR image into a number of key structures. This utilised a spatio-temporal atlas as tissue priors in an expectation-maximization approach with second order Markov random field (MRF) regularization to improve the accuracy of the cortical boundary estimate. An implicit high resolution surface was then used to compute cortical folding measures. We validated the automated segmentations with manual delineations and the average surface discrepancy was of the order of 1 mm. Eight curvature-based folding measures were computed for each fetal cortex and used to give summary shape descriptors. These were strongly correlated with GA (R2 = 0.99) confirming the close link between neurological development and cortical convolution. This allowed an age-dependent nonlinear model to be accurately fitted to the folding measures. The model supports visual observations that, after a slow initial start, cortical folding increases rapidly between 25 and 30 weeks and subsequently slows near birth. The model allows the accurate prediction of fetal age from an observed folding measure with a smaller error where growth is fastest. We also analysed regional patterns in folding by parcellating each fetal cortex using a nine-region anatomical atlas and found that Gompertz models fitted the change in lobar regions. Regional differences in growth rate were detected, with the parietal and posterior temporal lobes exhibiting the fastest growth, while the cingulate, frontal and medial temporal lobes developed more slowly.
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