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

Or R. Sadan, Netanell Avisdris, Aviad Rabinowich, Daphna Link-Sourani, Karina Krajden Haratz, Catherine Garel, Liran Hiersch, Liat Ben Sira, Dafna Ben Bashat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Cytomegalovirus (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. Purpose: To assess brain metabolite differences in CMV-infected fetuses using magnetic resonance spectroscopy (MRS). Study type: Retrospective. Subjects: Out 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 Strength: 3 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. Assessment: MRI findings were assessed by three radiologists, and metabolic ratios within the basal ganglia were calculated using LCModel. Statistical Tests: Analysis 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. Results: MRS 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). Conclusion: Reduced 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 Evidence: 3. Technical Efficacy: Stage 3.

Original languageEnglish
Pages (from-to)1133-1141
Number of pages9
JournalJournal of Magnetic Resonance Imaging
Volume61
Issue number3
DOIs
StateAccepted/In press - 2024

Funding

FundersFunder number
Israel Innovation Authority

    Keywords

    • NAA
    • brain
    • cytomegalovirus
    • fetal
    • magnetic resonance spectroscopy
    • normal-appearing brain tissue

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