Early micro- and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants
Rahul Chandwani1, Julia E Kline1, Karen Harpster2,3
1Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Insights
Very preterm infants at risk for cerebral palsy (CP) can be identified earlier. Diffusion MRI measures of sensorimotor white matter tracts at term-equivalent age are associated with early CP diagnosis, aiding presymptomatic detection.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Pediatric Neurology
Background:
- Infants born very preterm (VPT) face a high risk of motor impairments, notably cerebral palsy (CP).
- Current CP diagnosis often occurs late, delaying crucial early interventions.
- Identifying biomarkers for presymptomatic detection is essential for improving outcomes in VPT infants.
Purpose of the Study:
- To derive micro- and macrostructural measures of sensorimotor white matter tract integrity using diffusion MRI in VPT infants at term-equivalent age.
- To assess the association between these diffusion MRI-derived measures and the early diagnosis of CP.
- To investigate potential in vivo determinants of CP for presymptomatic detection and targeted interventions.
Main Methods:
- Prospective cohort study of 263 VPT infants (≤32 weeks gestational age).
- Diffusion and structural MRI acquired at term-equivalent age.
- Fixel-based (FB) analysis of diffusion MRI data to compute fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) for nine sensorimotor tracts.
Main Results:
- Early CP diagnosis was established based on consensus guidelines including abnormal MRI and neuromotor examination.
- Significantly reduced FD, FC, and FDC were observed in sensorimotor tracts of VPT infants diagnosed with CP.
- These associations remained significant after adjusting for potential confounders.
Conclusions:
- Diffusion MRI measures of sensorimotor white matter tract integrity at term-equivalent age are associated with early CP diagnosis in VPT infants.
- These findings highlight the potential of diffusion MRI for presymptomatic identification of CP.
- Understanding these white matter changes can inform the development of targeted interventions for VPT infants at risk of CP.
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.
