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To assess fetal brain findings and volumetric composition with MRI in a prospective cohort of confirmed Zika virus (ZIKV) infected fetuses from the current outbreak in Barranquilla, Colombia.
Study Design
Between December 2015 and July 2016, 214 pregnant patients with suspected symptomatic ZIKV exposure (and their sexual partner/s) were included. Cases with fetal brain anomalies on ultrasound(US) and confirmed ZIKV (by qRT-PCR) underwent a fetal MRI (1.5 T Phillips Ingenia). In order to create a single 3D volume absent of artifact from inherent motion and intensity corruption, a super-resolution (SR) reconstruction was obtained by co-registering the 3 orthogonal T2 weighted image stacks and iteratively performing voxel-based intensity matching. SR images were post-processed for volumetric analyses by performing manual segmentation. Total Brain Volume (TBV), supratentorial brain parenchyma (SBP), ventricular volume (VV), brainstem volume (BV), cerebellar volume (CV), and total intracranial volume (TICV) (TBV + volume of CSF in the subarachnoid space) were determined.
Results
A total of 13 cases presented with abnormal brain US findings (microcephaly, ventriculomegaly, callosal dysgenesis, calcifications and cortical anomalies). Seven of those cases that were ZIKV positive underwent a fetal MRI (29.0±4.4 weeks), and were gestational age matched to 7 healthy controls (CTRLS) (29.87±4.61 weeks; p=0.72). ZIKV infected fetuses significantly differed from controls in TBV (ZIKV: 9422.42±2169.11 vs. CTRLS: 20529.7±7049.95; p<0.01) and TICV (16390.42±3690.41 vs.35593.42±12281.71; p<0.01). No significant difference was seen in VV (2692.85±540.92 vs. 2967.14±759.74; p=0.45), BV (653.01±211.51 vs. 990.22±369.31; p=0.06) or CV (914.31±414.57 vs. 1416.14±565.85; p=0.08). The CSF/SBP ratio was higher (1.36±0.20 vs. 0.99±0.16; p<0.01) in ZIKV affected fetuses, suggesting microencephaly.
Conclusion
In this large cohort of ZIKV infected gravidae, we characterized brain findings using MRI. Microcephaly, callosal dysgenesis, ventriculomegaly and calcifications are common anomalies associated with fetal ZIKV. We observed a significant association between decreased brain volumes (predominantly evidenced by decreased SBP and increased CSF in the subarachnoid space) and ultrasound detected microcephaly.