Eileen Hwuang1, M. Dylan Tisdall1, Nadav Schwartz1, John A. Detre1, and Walter R. Witschey1
1University of Pennsylvania, Philadelphia, PA, United States
Synopsis
While measuring uterine artery (UtA) impedance is commonly used to assess for risk of preeclampsia and intrauterine growth restriction, little is understood about the remodeling process during gestation. An improved understanding of geometrical changes can lead to predictive biomarkers of adverse pregnancies. Here we present a method of measuring path length and curvature of the tortuous UtAs by segmentation and centerline extraction of time-of-flight MR angiography. We show in 8 pregnant subjects in the 2nd and 3rd trimester that this technique is feasible for investigating longitudinal trends of UtA remodeling and cases of maladaptation.
Purpose
During pregnancy, the maternal uterine
arteries (UtAs) undergo vasodilation and elongation to accommodate the gravid
uterus and match fetal demand for oxygen and nutrients [1]. Maternal arterial dysfunction is characteristic of pregnancy disorders
such as preeclampsia [2] and patients have inward smooth muscle hypertrophy, increased wall
thickness, and limited vasodilation at delivery [3]. However, there is limited quantitative information about temporal
remodeling of UtAs. This information may add value to diagnosis and screening
of hypertensive pregnancy disorders [1]. We have shown that noninvasive, non-contrast MRI is feasible for characterization
of UtA anatomy and hemodynamics in humans [4]. Our objective was to quantitatively describe the geometry of the
pelvic arteries in healthy pregnant subjects using time-of-flight (TOF) MRI
angiography. We hypothesize that the UtA lengthens and becomes more tortuous
with gestational age.Methods
We analyzed TOF MRI data (Fig. 1a) from 8 healthy pregnant subjects (n=2 in the 2nd trimester, and n=6 in the 3rd trimester, gestational age = 29.9±2.8 weeks). The TOF parameters were: TR=394 ms, TE=4.4 ms, flip angle=50°, and diastolic ECG-gating. The TOF angiogram was segmented (Seg3D), isosurfaces and centerlines were generated, and length and curvature were quantified (VMTK) (Fig. 1b). The centerline connected the center points of maximally-inscribed spheres, approximated by a Voronoi diagram, along the interior of the vessel. The curvature, $$$\kappa$$$, was defined as the reciprocal of the radius, $$$r$$$, of the osculating circle ($$$\kappa=\frac{1}{r}$$$) tangent to the centerline in the normal direction using the Frenet reference system (Fig. 1c). Vessel tortuosity was measured using the root mean squared (RMS) curvature. Pearson’s R correlation was performed to test for linear correlations between path length, RMS curvature, and gestational age.Results
Figure 2a shows the centerline and UtA
curvature histograms of a representative subject (Fig. 2b,c). The UtAs formed a
tortuous structure, looped superiorly, and crossed the external iliac arteries
towards the placenta at the fundus of the uterus. Subject demographics and geometric
quantities, anatomical length, curvature for all subjects are reported in Figure
3. The unilateral length of the UtAs from
the bifurcation of the internal and external iliac arteries to the most
inferior point of the UtAs was 130.5 ± 21.0 mm (range = 92.4-161.4 mm). We
observed an increasing trend (R2 = 0.12, p = 0.18) between
gestational age and unilateral length (Fig. 4). The RMS curvature was found to
be 0.12 ± 0.04 mm-1 (range = 0.07-0.19 mm-1) within the
same UtA segments. There was a decreasing trend between gestational age and RMS
curvature from the bifurcation to the most inferior point of the UtA (R2
= 0.07, p = 0.30; Fig. 5). The difference between the left and right UtA length
was 13±6% and RMS curvature was 25±19%. Discussion
This study demonstrated quantitative
characterization of UtA length and curvature geometry using TOF MRI
angiography. Curvature was found to be a quantitatively meaningful descriptor
of UtA tortuosity and could differentiate bilateral UtA anatomical
heterogeneity. This may reflect variations in placental location, viability and
distal uterine and spiral arterial remodeling. Additionally, this study
provided important preliminary data regarding the association between UtA
length, curvature and gestational age. It was expected that the UtA path length
would increase during angiogenesis and become more tortuous to accommodate
fetal growth and decreasing blood flow pulsatility. However, we saw a decrease
in curvature. Based on our initial findings, to detect a 20 mm difference in
length between 2nd and 3rd trimester, we would need a
sample of 18 subjects. Similarly, to detect a 0.04 mm‑1 difference
in curvature, we would need 16 subjects. UtA remodeling is believed to rapidly
occur within the first two trimesters to anticipate increased fetal oxygen and
metabolic demand, tapering off by 3rd trimester [1, 5]. We
observed that path length and curvature vary considerably with laterality.
Future work will investigate curvature and tortuosity in patients with adverse
pregnancy outcomes.Conclusions
The major contributions of this study are 1)
the development an approach to measuring length and curvature of the UtAs, and
2) trends toward UtA elongation and decreased tortuosity with gestational age. Additional
subjects will confirm that these trends are consistent with UtA remodeling in animals
[1]. This
approach is applicable to studying UtA remodeling early in pregnancy and can be used to investigate the
relationship between vascular geometry and hemodynamics.Acknowledgements
National Child Health and Human Development (U01-HD087180); National Science Foundation (DGE-1321851); National Institute of Biomedical Imaging and Bioengineering (T32-EB009384); National Institute of Biomedical Imaging and Bioengineering (P41-EB015893); National Heart Lung and Blood Association (R00-HL108157); National Child Health and Human Development (R00-HD074649) References
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