Early micro- and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants

Rahul Chandwani, Julia E Kline, Karen Harpster, Jean Tkach, Nehal A Parikh, Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Group, Rahul Chandwani, Julia E Kline, Karen Harpster, Jean Tkach, Nehal A Parikh, Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Group

Abstract

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro- and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term-equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3-4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole-brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel-based (FB) analysis to compute fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) for each tract. Of 223 VPT infants with high-quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants.

Keywords: White matter; cerebral palsy; diffusion MRI; neonatology; preterm birth.

Conflict of interest statement

The authors declare no potential conflict of interest.

© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

Figures

FIGURE 1
FIGURE 1
Group fixel template and whole brain tractograph used to segment sensorimotor white matter tracts. (a–c) Group average fixel map showing the fiber orientation distribution (fOD) for all voxels in axial, coronal, and sagittal views, respectively; (d–f) Corresponding whole‐brain tractograph produced from the group average fOD template. Color indicates fiber trajectory. Each tractography figure shows green (anterior to posterior), red (left to right), and blue/purple (superior to inferior) fibers
FIGURE 2
FIGURE 2
Bilateral and unilateral segmentations of sensorimotor tracts. (a) Corticospinal tract in coronal view; (b) superior thalamic radiations (motor) in coronal view; (c) superior thalamic radiations (sensory) in coronal view; (d) posterior thalamic radiations in axial view; (e) corpus callosum in sagittal view; (f) corpus callosum in axial view. All fibers of the STRS and CC are not visible in a single view, as the tracts continue from the thalamus to the postcentral gyrus and from the splenium to the posterior brain, respectively. Color indicates fiber trajectory. Each tractography figure shows green (anterior to posterior), red (left to right), and blue/purple (superior to inferior) fibers

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