Longitudinal Placental Blood Volume Measurements in Zika-Infected Rhesus Macaques Using Ferumoxytol Enhanced MRI.

Abstract

Introduction: Measures of maternal fractional blood volume (mFBV) in the placenta holds potential to diagnose placental vasculature deficiencies. However, methods for quantitative mapping of blood volume are challenging to implement for clinical placenta evaluation. As a preliminary step towards human applications, this study assesses the feasibility of blood volume measurements using ferumoxytol enhanced variable flip angle (VFA) T1-mapping in Zika-infected rhesus macaques.

Methods: Seven pregnant rhesus macaques were imaged longitudinally at up to 3 timepoints across gestation (days 64.5±1.9, 100.8±3.9, and 145.3±1.8), corresponding to first, second, and third pregnancy trimester of the rhesus. Four animals received a Zika virus (ZIKV) injection into the amniotic fluid, while three control rhesus macaques received a saline injection. T1-weighted spoiled gradient echo sequences at four flip angles (2°, 6°, 10°, 14°) were used for quantitative mFBV assessment derived from pre- and post-contrast T1 mapping using ferumoxytol. Image quality assessment and segmentation assessment was performed on the full 3D coverage. Placental histopathology for all animals was analyzed by a professional pathologist with over 15 years of experience.

Results: All scans were successfully acquired and analyzed with no significant motion artifacts. 3D mFBV maps show regional heterogeneities within slices. FBV and total placental blood volume has an increasing trend with gestation.

Discussion: This study shows feasibilities to measure mFBV in non-human primates using ferumoxytol enhanced VFA T1-mapping.