Functional Imaging of the Non-Human Primate Placenta With Endogenous BOLD Contrast
Matthias C Schabel1,2, Victoria H.J. Roberts3, Jamie O. Lo3, Antonio E. Frias4, and Chris D. Kroenke1

1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, 2Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, United States, 3Division of Diabetes, Obesity, and Metabolism, Oregon Health & Science University, Portland, OR, United States, 4Division of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, United States

Synopsis

We describe a non-contrast method for assessing placental perfusion and fetal oxygenation status utilizing quantitative T2* mapping and a novel spatial model, and validate our method using DCE-MRI measurement in pregnant rhesus macaques.

Purpose:

To characterize spatial patterns of T2* in the rhesus macaque placenta, to correlate these patterns with placental perfusion determined using DCE-MRI, and to evaluate the potential for using the BOLD effect to quantify placental perfusion without the use of exogenous contrast reagent.

Methods:

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 T2*. 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 T2* 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 R2* within a single placental lobule to relevant underlying physiological parameters. This model predicts that the spatial variation of R2* 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 R20* is the intrinsic R2* in the absence of deoxyhemoglobin (Hbd), r2* is the R2* relaxivity of Hbd, [Hb] is the total maternal hemoglobin concentration, [Hbo,f] is the effective concentration of oxyhemoglobin in the fetal arterial blood, [Hbo,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, vi 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, [Hbo,in] from maternal arterial pulse oximetry, and the experimental r2* value for deoxyhemoglobin, this equation can be fit to measured data to estimate R20*, [Hbo,f], and vi PS/Φ for individual lobules within the placenta.

Results:

Local maxima in T2* maps are strongly correlated with spiral arteries identified by DCE-MRI, with mean spatial separations ranging from 2.34 to 6.11 mm in the three animals studied. Spatial patterns of R2* within individual placental lobules can be quantitatively analyzed using a simple model to estimate fetal arterial oxyhemoglobin concentration [Hbo,f] and a parameter, vi PS/Φ, reflecting oxygen transport to the fetus. Estimated mean values of [Hbo,f] ranged from 4.25 mM to 4.46 mM, while vi PS/Φ ranged from 2.80×105 cm-3 to 1.61×106 cm-3.

Discussion:

Many aspects of placental growth, development, and function are poorly understood as a result of the lack of non-invasive tools for their assessment in vivo. We have developed a novel application of blood oxygen level dependent (BOLD) MRI that allows in-vivo assessment of placental perfusion and fetal oxygen saturation and have compared the results with dynamic contrast-enhanced (DCE) MRI imaging in pregnant rhesus macaques. Maternal spiral arteries identified on contrast-enhanced imaging show strong spatial correlation with foci of extended T2* observed in the primate placenta. A simple model of oxygen transport accurately describes the spatial dependence of R2* within placental lobules and enables assessment of placental function and oxygenation without requiring administration of an exogenous contrast reagent.

Conclusion:

It is possible to non-invasively assess placental perfusion and fetal oxygenation status in vivo using quantitative T2* relaxometry using a novel model describing the spatial distribution of T2* within placental lobules. This non-contrast method may provide a means for identifying abnormal placental development and facilitate early intervention for high-risk pregnancies.

Acknowledgements

Grant Support:

R01 HD086331

U01 HD087182

R01 AA021981

P51 OD011092

R24 DK090964

R21 HD076265

References

(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.

Figures

A comparison of T2* 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 T2* map corresponding to (a), with local maxima indicated by blue circles. (d) shows the relative enhancement data at 25.5 seconds post-injection, with T2* maxima from (c) overlaid. Placental lobes are delineated by green dashed lines.

Spatial dependence of measured R2* along with model fit and prediction sensitivity to changes in blood flow and maternal oxygen saturation. Black points show measured R2* as a function of ρeff 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 vi PS/Φ, panel (b) shows R20*, and panel (c) shows [Hbo,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