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 T
2* 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 T
2* 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 R
2* within individual placental lobules can be
quantitatively analyzed using a simple model to estimate fetal arterial
oxyhemoglobin concentration [Hb
o,f] and a parameter, v
i PS/Φ, reflecting oxygen transport to the fetus. Estimated mean values of [Hb
o,f] ranged from
4.25 mM to 4.46 mM, while v
i PS/Φ ranged
from 2.80×10
5 cm
-3 to 1.61×10
6 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 T
2* observed in the
primate placenta. A simple model of oxygen transport accurately describes the
spatial dependence of R
2* 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.