ESA-SRB-AOTA 2019

Detection of reduced oxygenation in 3D placental volumes by magnetic resonance imaging (MRI) in a rat model of fetal growth restriction (FGR) (#694)

Yutthapong Tongpob 1 2 , Alexander Joos 3 , Caitlin Wyrwoll 1 , Kirk Feindel 3 4
  1. School of Human Sciences, The University of Western Australia, Perth, WA, Australia
  2. Department of Anatomy, Faculty of Medical Sciences, Naresuan University, Phitsanulok, Thailand
  3. Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, WA, Australia
  4. School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia

A key driver of FGR is placental insufficiency, including inadequate development of placental vasculature. However, there are currently limitations in assessing placental function in-vivo. MRI can measure relaxation time (T2*), which correlates with oxygenation via alterations in blood haemoglobin saturation. Results of previous placental T2* studies have been conflicting, due to technical and analytical challenges, including consideration of only 2D-regions of interest (ROI).

This study utilised a 3D-MRI approach in a rat model of FGR.

Time-mated rats were treated with either vehicle (Veh) or dexamethasone (Dex; 0.5μg/ml) in drinking water from embryonic day (E)13 onwards. Serial scans at E15, E18, and E21 were conducted using a 9.4T MRI in-vivo: a 3D-multi-gradient-echo sequence with oxygen challenge (oxygen vs medical-air) to obtain 3D-maps of the T2* signal. E21 dams were euthanised, feto-placental units dissected, and weighed. E21 T2*-values were calculated for manually defined 3D-ROIs with custom-Matlab software using the SQEXP algorithm, which is better suited for low signal to noise data than standard algorithms. In a separate cohort of rats, feto-placental vascular casts were generated, scanned using micro-CT and quantified with custom-Matlab software.

E21 fetal and placental weights decreased in Dex rats by 15.6% and 35.2% respectively in comparison to Veh (p<0.0002). MRI scans revealed that when shifting from oxygen to medical-air, mean whole-placental T2* decreased in Veh and Dex by 35.2% and 20.9% respectively (p<0.05). Importantly, the relative shift in whole-placental T2* differed significantly between Veh and Dex (3.1+0.4 vs 2.0+0.5 msec; p<0.05), indicating reduced blood oxygenation in Dex placentas. Furthermore, the MRI measures aligned with a marked decline in feto-placental vascular complexity in Dex. 

Ongoing analyses are determining whether these changes are dynamic across gestation. The results of this proof-of-concept study demonstrate that T2*-based measurements of the placental blood oxygenation can provide non-invasive assessments of in-vivo placental health.