title: Tract shape modeling detects changes associated with preterm birth and neuroprotective treatment effects.
abstract: 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.
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK ; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Devasuda
authors.initials: D
authors.lastname: Anblagan
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sparrow
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Chinthika
authors.initials: C
authors.lastname: Piyasena
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Rozalia
authors.initials: R
authors.lastname: Pataky
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Moore
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Serag
authors.affiliation: Department of Radiology, Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK.
authors.forename: Alastair Graham
authors.initials: AG
authors.lastname: Wilkinson
authors.affiliation: Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Clayden
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Scott I
authors.initials: SI
authors.lastname: Semple
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK ; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Boardman
mesh_terms: D015415:Biomarkers; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008278:Magnesium Sulfate / Q000627:therapeutic use; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D066127:White Matter / Q000187:drug effects / Q000473:pathology*
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D008278:Magnesium Sulfate
keywords: Brain; Infant; Magnesium sulfate; Magnetic resonance image; Neuroprotection; Preterm