Apparent diffusion coefficient values of the white matter in magnetic resonance imaging of the neonatal brain may help predict outcome in congenital cytomegalovirus infection

Abstract

Background: White matter change is a well-known abnormality in congenital cytomegalovirus (cCMV) infection, but grading remains challenging and clinical relevance unclear.

Objective: To investigate if quantitative measurement of white matter apparent diffusion coefficient (ADC) values in magnetic resonance imaging (MRI) of the neonatal brain can predict outcome in cCMV.

Materials and methods: A retrospective, single-center observational study, including patients with cCMV who had a neonatal brain MRI with diffusion-weighted imaging, was performed between 2007 and 2020. Regions of interest were systematically placed in the white matter on the ADC maps. Two pediatric radiologists independently scored additional brain abnormalities. Outcome measures were neonatal hearing and cognitive and motor development. Statistical analysis included simple and penalized elastic net regression.

Results: Neonatal brain MRI was evaluated in 255 patients (median age 21 days, 25-75 percentiles: 14-28 days, 121 male). Gyral abnormalities were noted in nine patients (3.5%), ventriculomegaly in 24 (9.4%), and subependymal cysts in 58 (22.7%). General white matter ADC was significantly higher in patients with neonatal hearing loss and cognitive and motor impairment (P< 0.05). For neonatal hearing loss, simple logistic regression using only general white matter was the best prediction model, with a receiver operating characteristic area under the curve (AUC)=0.76. For cognitive impairment, interacting elastic net regression, including other brain abnormalities and frontoparietal white matter ADC, performed best, with AUC=0.89. For motor impairment, interacting elastic net regression, including other brain abnormalities and deep anterior frontal white matter performed best, with AUC=0.73.

Conclusion: Neonatal white matter ADC was significantly higher in patients with clinical impairments. Quantitative ADC measurement may be a useful tool for predicting clinical outcome in cCMV.

Keywords: Brain; Cytomegalovirus infection; Follow-up studies; Hearing loss; Magnetic resonance imaging; Newborn; White matter.

Fig. 1

Axial apparent diffusion coefficient magnetic resonance images in a 2-week-old boy with congenital cytomegalovirus infection show placement of regions of interest (arrows) in the subcortical frontoparietal white matter (a), posterior periventricular white matter (b), deep anterior frontal white matter (thin arrows in c), thalami (thick arrows in c), anterior temporal white matter (d), and cerebellar hemispheres (e)

Fig. 2

Results of the ten elastic net models per outcome: neonatal hearing (a), and cognitive (b) and motor (c) development. For each model, mean receiver operating characteristic area under the curve (mean ROC AUC) ± 1 standard error (SE) is shown. ADC apparent diffusion coefficient, PV posterior periventricular

Fig. 3

Cross-validated receiver operating characteristic curves for neonatal hearing (a), and cognitive (b) and motor (c) development