Brain Metabolite Differences in Fetuses With Cytomegalovirus Infection: A Magnetic Resonance Spectroscopy Study

Abstract

BackgroundCytomegalovirus (CMV) is the most common intrauterine infection and may be associated with unfavorable outcomes. While some CMV‐infected fetuses may show gross or subtle brain abnormalities on MRI, their clinical significance may be unclear. Conversely, normal development cannot be guaranteed in CMV‐infected fetuses with normal MRI.PurposeTo assess brain metabolite differences in CMV‐infected fetuses using magnetic resonance spectroscopy (MRS).Study typeRetrospective.SubjectsOut of a cohort of 149 cases, 44 with maternal CMV infection, amniocentesis results, and good‐quality MRS were included. CMV‐infected fetuses with positive polymerase chain reaction (PCR) (N = 35) were divided based on MRI results as follows: typical brain abnormalities (gross findings, N = 8), exclusive white matter hyperintense signal (WMHS) on T2‐weighted images (subtle findings, N = 7), and normal MRI (N = 20). Uninfected fetuses (negative PCR) with normal MRI were included as controls (N = 9).Field Strength3 T, T2‐weighted half Fourier single‐shot turbo spin‐echo (HASTE), T2‐weighted true fast imaging with steady‐state free precession (TrueFISP), T1‐ and T2*‐weighted fast low angle shot (FLASH), and 1H‐MRS single‐voxel point resolved spectroscopy (PRESS) sequences.AssessmentMRI findings were assessed by three radiologists, and metabolic ratios within the basal ganglia were calculated using LCModel.Statistical TestsAnalysis of covariance test with Bonferroni correction for multiple comparisons was used to compare metabolic ratios between groups while accounting for gestational age. A P‐value <0.05 was deemed significant.ResultsMRS was successfully acquired in 63% of fetuses. Substantial agreement was observed between radiologists (Fleiss' kappa [k] = 0.8). Infected fetuses with gross MRI findings exhibited significantly reduced tNAA/tCr ratios (0.64 ± 0.08) compared with infected fetuses with subtle MRI findings (0.85 ± 0.19), infected fetuses with normal MRI (0.8 ± 0.14) and controls (0.81 ± 0.15). No other significant differences were detected (P ≥ 0.261).ConclusionReduced tNAA/tCr within the apparently normal brain tissue was detected in CMV‐infected fetuses with gross brain abnormalities, suggesting extensive brain damage. In CMV‐infected fetuses with isolated WMHS, no damage was detected by MRS.Level of Evidence3Technical EfficacyStage 3