Fractal-dimension analysis detects cerebral changes in preterm infants with and without intrauterine growth restriction

In the search for a useful parameter to detect and quantify subtle brain abnormalities in infants with intrauterine growth restriction (IUGR), we hypothesised that the analysis of the structural complexity of grey matter (GM) and white matter (WM) using the fractal dimension (FD), a measurement of the topological complexity of an object, could be established as a useful tool for quantitative studies of infant brain morphology.We studied a sample of 18 singleton IUGR premature infants, (12.72 months corrected age (CA), range: 12 months–14 months), 15 preterm infants matched one-to-one for gestational age (GA) at delivery (12.6 months; range: 12 months–14 months), and 15 neonates born at term (12.4 months; range: 11 months–14 months). The neurodevelopmental outcome was assessed in all subjects at 18 months CA according to the Bayley Scale for Infant and Toddler Development – Third edition (BSID-III). For MRI acquisition and processing, the infants were scanned at 12 months CA, in a TIM TRIO 3T scanner, sleeping naturally. Images were pre-processed using the SPM5 toolbox, the GM and WM segmented under the VBM5 toolbox, and the box-counting method was applied for FD calculation of normal and skeletonised segmented images.The results showed a significant decrease of the FD of the brain GM and WM in the IUGR group when compared to the preterm or at-term controls. We also identified a significant linear tendency of both GM and WM FD from IUGR to preterm and term groups. Finally, multiple linear analyses between the FD of the GM or WM and the neurodevelopmental scales showed a significant regression of the language and motor scales with the FD of the GM.In conclusion, a decreased FD of the GM and WM in IUGR infants could be a sensitive indicator for the investigation of structural brain abnormalities in the IUGR population at 12 months of age, which can also be related to functional disorders.

Research highlights
► We found a significant decrease of the fractal dimension (FD) of the brain grey matter (GM) and white matter (WM) in 12 months old infants with intrauterine growth restriction (IUGR) when compared to preterm or at-term controls.
► We also identified a significant linear tendency of both GM and WM FD from IUGR to preterm and term groups.
► Multiple linear analyses between the FD of the GM or WM and neurodevelopmental scales showed a significant regression of the language and motor scales with the FD of the GM.
► The FD of the GM and WM in IUGR infants could be a sensitive indicator of structural brain abnormalities in the IUGR population at 12 months of age.