Associations between diffusion kurtosis imaging metrics and neurodevelopmental outcomes in neonates with low-grade germinal matrix and intraventricular hemorrhage

Abstract

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695-0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722-0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657-0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712-0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.

Keywords: Diffusion kurtosis imaging; Germinal matrix hemorrhage-intraventricular hemorrhage; Neonates; Neurodevelopmental outcomes; Quantitative MRI.

Figure 1

Flowchart shows inclusion and exclusion criteria for neonates. DKI Diffusion kurtosis imaging, Bayley—II Bayley Scales of Infant and Toddler Development 2nd Edition, low-grade GMH-IVH low-grade Germinal Matrix Hemorrhage-Intraventricular Hemorrhage.

Figure 2

Representative neonatal images (T₁WI, T₂WI, FA, MK, and RK) without (top row) and with (bottom row) low-grade GMH-IVH. (A-E) showcases a male neonate with a gestational age of 31 weeks, corrected gestational age at MRI scan is 38 weeks, with Bayley—II scores of MDI and PDI at 125 and 121. (F-J) features a male neonate with a gestational age of 30 weeks, corrected gestational age at MRI scan is 38 weeks, and Bayley—II scores of MDI and PDI at 93 and 100. DKI Diffusion kurtosis imaging, FA Fractional anisotropy, MK mean kurtosis, RK radial kurtosis, low-grade GMH-IVH low-grade Germinal Matrix Hemorrhage-Intraventricular Hemorrhage, Bayley—II Bayley Scales of Infant and Toddler Development 2nd Edition, MDI Mental Development Index, PDI Psychomotor Development Index.

Figure 3

Correlation between DKI-derived metrics or volume and MDI and PDI scores at 18 months for neonates with low-grade GMH-IVH. (A–D) Pearson correlation between MK or RK in the thalamus and MDI or PDI scores. (E–H) The relationship between MK or RK in the PLIC and MDI or PDI scores. (I,J) The correlation between RK in the caudate nucleus and MDI or PDI scores. DKI Diffusion kurtosis imaging, MDI Mental Development Index, PDI Psychomotor Development Index, MK mean kurtosis, RK radial kurtosis, low-grade GMH-IVH  low-grade Germinal Matrix Hemorrhage-Intraventricular Hemorrhage, PLIC Posterior Limbs of the Internal Capsule.