Diffusional kurtosis imaging in neonatal encephalopathy

Moss HG, Yazdani M, Jensen JH, Katikaneni L, Wiest DB, Wagner CL, Jenkins DD. Neonatal encephalopathy: a diffusional kurtosis imaging analysis of white matter to assess injury severity and recovery. Pediatr Res. 2025 Oct 30. doi: 10.1038/s41390-025-04434-x. Epub ahead of print. PMID: 41168400.

Abstract

Background: Diffusional kurtosis imaging (DKI) may be more sensitive to white matter (WM) injury than diffusion tensor imaging (DTI) in infants with neonatal encephalopathy (NE) presumed from hypoxic ischemic encephalopathy (HIE). We hypothesized that DKI would differentiate encephalopathy severity, predict outcomes, and indicate treatment response.

Methods: DKI was acquired using 3 T MRI in neonates with HIE on day 4-10 following hypothermia (n = 21, HIE-C), or day 5-6 (n = 16, NVD-A) and 2-6 weeks (n = 18, NVD-R) in infants who received N-acetylcysteine and vitamin D (NVD) with hypothermia. We utilized tensor-derived diffusion metrics in generalized linear models to estimate Peabody Gross Motor, Cognitive Adaptive, Clinical Linguistic, and Auditory Milestones test scores.

Results: Mean kurtosis differentiated stage 3 and 2 encephalopathy in all cohorts. The recovery scan predicted outcomes better than the acute scan. Kurtosis metrics and Vitamin D dose were significant determinants of gross motor and cognitive scores in NVD-R group.

Conclusion: Kurtosis reflects the degree of acute CNS injury and was sensitive to treatment effects in term infants with a clinical diagnosis of HIE. Our data are consistent with prior work in adult stroke, which indicates that diffusivity and kurtosis at different stages of recovery capture distinct aspects of WM injury.

Impact: Diffusional kurtosis imaging (DKI) is an advanced diffusion MRI modality rarely applied in pediatric imaging that quantifies the complexity of water movement in white matter (WM), and which offers increased sensitivity to the severity of injury and recovery after neonatal encephalopathy due to presumed hypoxic-ischemic brain injury. We demonstrate that kurtosis in early-myelinating WM tracts differentiates the severity of neonatal encephalopathy (NE) better than diffusivity, which may have therapeutic implications. DKI provides complementary information about WM injury and recovery after NE beyond current methods, which are lacking in subjective clinical MRI assessments. DKI indicates the effect of therapeutics on WM injury in NE.