Tract shape modeling detects changes associated with preterm birth and neuroprotective treatment effects

•Probabilistic neighborhood tractography models tract shape from neonatal dMRI.•The shape of major fasciculi is altered in association with preterm birth.•Developing neural systems are separable based on dMRI parameters.•Tract-averaged dMRI parameters are sensitive to neuroprotective treatment effects.

Preterm birth is associated with altered connectivity of neural circuits. We developed a tract segmentation method that provides measures of tract shape and integrity (probabilistic neighborhood tractography, PNT) from diffusion MRI (dMRI) data to test the hypotheses: 1) preterm birth is associated with alterations in tract topology (R), and tract-averaged mean diffusivity (〈D〉) and fractional anisotropy (FA); 2) neural systems are separable based on tract-averaged dMRI parameters; and 3) PNT can detect neuroprotective treatment effects.dMRI data were collected from 87 preterm infants (mean gestational age 29+1 weeks, range 23+2 –34+6) at term equivalent age and 24 controls (mean gestational age 39+6 weeks). PNT was used to segment eight major fasciculi, characterize topology, and extract tract-averaged 〈D〉 and FA.Tract topology was altered by preterm birth in all tracts except the splenium (p < 0.05, false discovery rate [FDR] corrected). After adjustment for age at scan, tract-averaged 〈D〉 was increased in the genu and splenium, right corticospinal tract (CST) and the left and right inferior longitudinal fasciculi (ILF) in preterm infants compared with controls (p < 0.05, FDR), while tract-averaged FA was decreased in the splenium and left ILF (p < 0.05, FDR). Specific fasciculi were separable based on tract-averaged 〈D〉 and FA values. There was a modest decrease in tract-averaged 〈D〉 in the splenium of preterm infants who had been exposed to antenatal MgSO4 for neuroprotection (p = 0.002).Tract topology is a biomarker of preterm brain injury. The data provide proof of concept that tract-averaged dMRI parameters have utility for evaluating tissue effects of perinatal neuroprotective strategies.