A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia

Abstract

Objective: To assess the predictive value of a novel magnetic resonance imaging (MRI) score, which includes diffusion-weighted imaging as well as assessment of the deep grey matter, white matter, and cerebellum, for neurodevelopmental outcome at 2 years and school age among term infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

Study design: This retrospective cohort study (cohort 1, The Netherlands 2008-2014; cohort 2, Sweden 2007-2012) including infants born at >36 weeks of gestational age treated with therapeutic hypothermia who had an MRI in the first weeks of life. The MRI score consisted of 3 subscores: deep grey matter, white matter/cortex, and cerebellum. Primary adverse outcome was defined as death, cerebral palsy, Bayley Scales of Infant and Toddler Development, third edition, motor or cognitive composite scores at 2 years of <85, or IQ at school age of <85.

Results: In cohort 1 (n = 97) and cohort 2 (n = 76) the grey matter subscore was an independent predictor of adverse outcome at 2 years (cohort 1, OR, 1.6; 95% CI, 1.3-1.9; cohort 2, OR, 1.4; 95% CI, 1.2-1.6), and school age (cohort 1, OR, 1.3; 95% CI, 1.2-1.5; cohort 2, OR, 1.3; 95% CI, 1.1-1.6). The white matter and cerebellum subscore did not add to the predictive value. The positive predictive value, negative predictive value, and area under the curve for the grey matter subscore were all >0.83 in both cohorts, whereas the specificity was >0.91 with variable sensitivity.

Conclusion: A novel MRI score, which includes diffusion-weighted imaging and assesses all brain areas of importance in infants with therapeutic hypothermia after perinatal asphyxia, has predictive value for outcome at 2 years of age and at school age, for which the grey matter subscore can be used independently.

Keywords: MRI; hypothermia; hypoxic-ischemic encephalopathy; outcome; score.

Figure 1

MRI examples of all items to be scored with the novel MRI score. The abnormalities of interest are marked by the white arrows. A, Focal bilateral thalamic lesions (high signal intensity [SI]) on an axial DWI. B, Extensive bilateral thalamic lesions (low SI) on an axial ADC map. C, Focal bilateral lesions (high SI) in the basal ganglia on an axial DWI. D, Extensive bilateral lesions (high SI) in the basal ganglia on an axial DWI. E, The posterior limb of the internal capsule (PLIC) is equivocal on both sides on an axial inversion recovery (IR) image. F, Absent PLIC bilaterally seen as an inverted signal (low SI) on an axial T1-weighted image (T1WI). G, Focal lesion (high SI) in the left cerebral peduncle on an axial DWI. H, Extensive diffusion changes (high SI) in the cerebral peduncles bilaterally on an axial DWI. I, Clear involvement (high SI) of the perirolandic gyrus bilaterally on an axial DWI. J, Bilateral involvement (low SI) of the hippocampus on an axial ADC map. K, Focal involvement (high SI) of the left cortex on an axial DWI. L, Extensive bilateral involvement of the cortex, seen as loss of the differentiation between the white matter and cortical grey matter in the occipital and frontal lobes bilaterally. M, Focal unilateral abnormal signal (low SI) in the left periventricular white matter on an axial ADC map. N, Extensive involvement of the white matter (high SI) on an axial DWI. O, Bilateral punctate white matter lesions (PWML) seen as high SI on an axial DWI. P, A small focal hemorrhage in the right occipital lobe (low SI) on an axial T2-weighted image (T2WI). Q, Bilateral involvement of the optic radiation (high SI) on an axial DWI. R, Involvement of the frontal part of the corpus callosum (high SI) on an axial DWI. S, Focal lesion (high SI) in the left cerebellar hemisphere on an axial T1WI. T, Extensive involvement of both cerebellar hemispheres (high SI) on an axial DWI. U, Bilateral intraventricular hemorrhage (IVH) seen as low SI on an axial T2WI. V, Subdural hemorrhage (SDH) supra- and infratentorial seen as high SI on a sagittal T1WI. W, Cerebral sinovenous thrombosis (CSVT) seen as high SI at the location of the superior sagittal and straight sinus on a sagittal T1WI. X, With corresponding lack flow (lack of high SI) in those veins on an MR venography (MRV) in sagittal view.

Figure 2

Individual score values on the grey matter subscore for infants with a normal (open circles) and infants with an abnormal outcome (death, black crosses; CP, black squares; other impairment, open squares) A, B, at 2 years of age; and C, D, at school age; A, C, in cohort 1; and B, D, cohort 2. The black horizontal lines indicate the median. The dotted horizontal lines indicate the cutoff values for risk of adverse outcome.

Figure 3

Predicted probability of death or impairment A, at 2 years of age and B, at school age based on the grey matter subscore in cohort 1.