332 - Alterations in MRI biomarkers of myelination associated with preterm birth

Poster Number: 332
Publication Number: 332.442

Kadi Vaher, University of Edinburgh, Edinburgh, Scotland, United Kingdom; Manuel Blesa, University of Edinburgh, Edinburgh, Scotland, United Kingdom; Michael Thrippleton, University of Edinburgh, Edinburgh, Scotland, United Kingdom; Elizabeth N. York, University of Edinburgh, Edinburgh, Scotland, United Kingdom; Paola Galdi, MRC Centre for Reproductive Health, University of Edinburgh, UK, Edinburgh, Scotland, United Kingdom; Gemma Sullivan, University of Edinburgh, Edinburgh, Scotland, United Kingdom; David Q. Stoye, National Health Service, St. Albans, England, United Kingdom; Jill Hall, University of Edinburgh, Edinburgh, Scotland, United Kingdom; Amy E. Corrigan, University of Edinburgh, Edinburgh, Scotland, United Kingdom; Alan J. Quigley, NHS Lothian, Edinburgh, Scotland, United Kingdom; Mark Bastin, University of Edinburgh, Edinburgh, Scotland, United Kingdom; Debby Bogaert, University of Edinburgh, edinburgh, Scotland, United Kingdom; James P. Boardman, University of Edinburgh, Edinburgh, Scotland, United Kingdom

Background: Myelination begins during the second trimester of pregnancy and is disrupted by preterm birth. Magnetisation transfer (MT) imaging is based on the exchange of magnetisation between immobile protons in macromolecules and mobile protons in free water. It is sensitive to myelin- and oligodendrocyte-associated macromolecules (e.g. cholesterol, myelin basic protein, sphingomyelin, galactocerebrides) and offers a surrogate marker for myelin integrity. MT ratio (MTR) has been used to study myelination in the developing brain and associates with cognitive outcomes in preterm children, but this measure is susceptible to B1 field inhomogeneities and longitudinal relaxation effects (R1=1/T1). MT saturation (MTSat) corrects for these effects and offers improved tissue contrast. Higher MTR and MTSat values associate with improved myelination.

Objective: To explore the effect of preterm birth on MTSat and other biomarkers of brain myelination in neonates

Design/Methods: 75 neonates (Table 1) of the Theirworld Edinburgh Birth Cohort underwent brain structural MRI and MT Imaging at term-equivalent age (TEA). MTR, MTSat, and approximation of longitudinal relaxation rate (R1app) maps were obtained. FSL randomise was used to perform voxel-wise analysis in the white matter (WM) and subcortical gray matter (GM) comparing term vs preterm infants, adjusting for age at scan. We also extracted average metric values for specific regions of interest (ROI) and compared term vs preterm infants adjusting for age at scan using general linear models.

Results: In voxel-wise analyses (Figure 1) preterm infants have lower R1 values in most of the WM and subcortical GM. MTR values are higher in preterm infants in most of the subcortical GM and parietal lobe WM; MTSat values are higher in term infants, particularly in the frontal lobe WM. Results replicate in ROI-based analyses (Figure 2).Conclusion(s): We observed higher MTR values in the parietal lobe WM and subcortical GM of preterm infants and no effect in MTSat in those regions. As MTR is affected by longitudinal relaxation, our results suggest this prematurity-related effect in MTR could be driven by other factors besides myelination, particularly cellular density and water content as indicated by the lower R1 values in preterm neonates. In contrast, frontal lobe WM showed higher MTSat values, which are decoupled from R1, in term infants but no differences in MTR. This could indicate decreased myelination-related processes in frontal lobe WM in preterm infants at TEA. MTSat offers a promising tool to reveal novel information about myelination in the developing brain.
KVaher_CV.pdf
Voxel-wise analysisFigure 1. Results of the voxel-wise analysis showing differences in magnetisation transfer imaging metrics in preterm infants at term-equivalent age versus term-born controls. The first row represents the mask (green) where voxel values were compared. Voxels that have higher values in the preterm group compared with the term group are indicated in red-yellow; voxels that have higher values in term group compared with preterm group are indicated in blue-light blue, overlaid on the ENA50 T2w image. Results are reported after 5000 permutations, threshold-free cluster enhancement and family-wise error correction for multiple comparisons with significance level set at p < 0.05. For visualisation: anatomic left is on the right side of the image. Nf75 infants (17 full-term; 58 preterm). MTR = magnetisation transfer ratio, MTSat = magnetisation transfer saturation, R1app = approximation of longitudinal relaxation rate.