Functional Imaging of the Non-Human Primate Placenta With Endogenous BOLD Contrast

Matthias C Schabel^{1,2}, Victoria H.J. Roberts^{3}, Jamie O. Lo^{3}, Antonio E. Frias^{4}, and Chris D. Kroenke^{1}

Magnetic resonance imaging
was performed on three pregnant rhesus macaques at gestational day 110.
Multi-echo spoiled gradient echo measurements were used to compute maps of T_{2}*. Spatial maxima in these maps were compared with foci
of early enhancement determined by DCE-MRI. We hypothesize that a
pattern of high-to-low T_{2}* observed with increasing spatial
distance from the spiral artery source within individual perfusion domains in
the placenta represents a high-to-low gradient in oxygen concentration in
maternal blood within the intervillous space. From this, we develop a
mathematical model relating the spatial distribution of R_{2}* within a single placental lobule to relevant underlying physiological
parameters. This model predicts that the spatial variation of R_{2}* within individual lobules as a
function of distance (ρ) from the spiral artery supplying oxygenated blood from the mother to
the fetus can be described by

$R_2^*(\rho)=(R_{20}^* + r_2^* ([Hb]-[Hb_{o,f}])) + r_2^*([Hb_{o,f}] - [Hb_{o,in}]) \exp{-\frac{4 \pi}{3} \frac{PS}{\Phi} v_i \rho^3}$

where R_{20}* is the intrinsic R_{2}* in the absence of deoxyhemoglobin (Hb_{d}), r_{2}* is the R_{2}* relaxivity of Hb_{d}, [Hb] is the total maternal hemoglobin concentration, [Hb_{o,f}] is the effective concentration of oxyhemoglobin in the fetal arterial blood, [Hb_{o,in}] is the maternal oxyhemoglobin concentration at the spiral artery outlet to the lobule, PS is the permeability-surface area product for oxygen exchange from the intervillous space to the fetal villi, v_{i} is the volume fraction of intervillous space, and Φ is the total spiral artery blood flow to the lobule (in ml/min). Using [Hb] values obtained from maternal blood draws, [Hb_{o,in}] from maternal arterial pulse oximetry, and the experimental r_{2}* value for deoxyhemoglobin, this equation can be fit to measured data to estimate R_{20}*, [Hb_{o,f}], and v_{i} PS/Φ for individual lobules within the placenta.

Grant Support:

R01 HD086331

U01 HD087182

R01 AA021981

P51 OD011092

R24 DK090964

R21 HD076265

(1) Schabel, MC, Roberts, VHJ, Lo, JO, Platt S, Grant, KA, Frias, AE, Kroenke, CD. Functional imaging of the non-human primate placenta with endogenous BOLD contrast. Magnetic Resonance in Medicine, in press, accepted for publication October 2015.

A comparison of T_{2}* imaging and DCE-MRI results for a single
imaging slice through a rhesus macaque placenta. (a) shows
signal magnitude for each of the 6 echoes. (b) plots
relative enhancement of DCE-MRI
measurements. (c) displays
the T_{2}* map corresponding to (a), with local maxima indicated by blue circles. (d) shows the relative enhancement data at 25.5 seconds
post-injection, with T_{2}* maxima from (c) overlaid. Placental lobes are delineated by green dashed lines.

Spatial dependence of measured R_{2}* along with model fit and prediction sensitivity
to changes in blood flow and maternal oxygen saturation. Black
points show measured R_{2}* as a function of ρ_{eff} for a single lobule from the animal shown in Figure 1.
The red curve is a model fit to Equation [1]. Blue and green
curves plot model predictions for a decrease in maternal SpO2 from 100% to
80% (blue) or a decrease of 40% in the spiral artery blood flow (green).

Box plots of model
parameter estimates for all three animals. Parameters for all lobules of both
placental lobes are included. Panel (a) shows v_{i} PS/Φ, panel (b) shows R_{20}*, and panel (c) shows [Hb_{o,f}], with Animal A on the left, Animal B in the middle,
and Animal C on the right in each panel.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)

1593