Ruta Deshpande

Fractional volume of placental vessels in women with diabetes using a novel stereological 3D power Doppler technique

OBJECTIVES In maternal diabetes the placenta is large with abnormal vascular development and increased villous volume. We used a novel stereological 3D power Doppler ultrasound technique to investigate differences in-vivo in the placental fractional volume of power Doppler signal (FrVol-PD) between women with and without diabetes. METHODS We recruited 17 pregnant women with pre-gestational diabetes and 20 controls, all with anterior placentae. Each subject had ultrasound scans (Voluson 730 Expert) every 4 weeks between 12 and 32 weeks gestation. 3D power Doppler data were acquired and the placenta manually outlined using VOCAL (4D View). Power Doppler signal within the resultant volume was counted in a 3D manner adapting the random but systematic techniques used in stereology. RESULTS Subjects were of similar age, BMI and parity. From 16 weeks the mean (SD) placental FrVol-PD was higher in the non-diabetic than in the diabetic group: 16 weeks - 0.125 (0.03) versus 0.108 (0.03), 20 weeks - 0.144 (0.05) versus 0.104 (0.03), 24 weeks - 0.145 (0.05) versus 0.128 (0.03), 28 weeks - 0.159 (0.05) versus 0.133 (0.02) and 32 weeks - 0.154 (0.03) versus 0.123 (0.04). These differences were significant between control and diabetic subjects [F(1,35) = 4.737, p = 0.036] and across gestation [F(3,140) = 8.294, p < 0.001]. CONCLUSION Using a novel stereological-based ultrasound technique we have demonstrated the reliability of this application in the placenta. This technique shows promise for non-invasive assessment of placental function: further studies are required to identify if structural changes in a diabetic placenta are accompanied by altered function, manifest as reduced perfusion demonstrable in-vivo.

OC22.05: Comparison of placental blood flow in the third trimester of normal and diabetic pregnancy using a novel stereological 3D power Doppler technique

Objectives: Lung hypoplasia (LH) is a clinically challenging lesion with high neonatal mortality and morbidity. Accurate prenatal prediction of LH severity in such lesions as congenital diaphragmatic hernia (CDH) is critical for prenatal counseling, management planning and fetal intervention strategies. Clinically, lack of response to maternal hyperoxia as evidenced by reduced pulsatility index (PI) in fetal pulmonary arteries (PA) has been suggested to be predictive of severe LH. PA Doppler indices including peak early diastolic reverse flow (PEDRF) and shorter acceleration (AT) to ejection time (ET) have also been proposed as clinically useful predictors of severe LH. None of these parameters, however, have been validated. Our objective is to identify the best Doppler parameter of more severe LH using a Nitrofen-induced CDH rat model. Methods: Pregnant Sprague-Dawley rats were fed 100 mg of Nitrofen (CDH in 50–60% offspring), dissolved in 1 ml olive oil or vehicle at day E9.5. At 20.5 days, PA Doppler indices were investigated before and after maternal hyperoxia (100% O2 for 10 minutes) using a vevo 770 ultrasound biomicroscope. The fetuses were then harvested, and the presence/absence of CDH and lung weight/body weight ratio (LW/BW) were assessed. Results: Maternal hyperoxia in 24 control fetuses (LW/BW = 0.033 ± 0.0040), resulted in a significant decrease in PI and PEDRF to peak systolic forward velocity (PSV) ratio (P = 0.03 and 0.02, respectively), whereas AT/ET did not change. Although Nitrofen exposed fetuses without CDH (n = 15, LW/BW = 0.027 ± 0.0053) demonstrated the same response as controls, Nitrofen-exposed fetuses with CDH and more severe LH (n = 12, LW/BW = 0.022 ± 0.0035) showed no significant change in PA Doppler parameters in response to maternal hyperoxia. Conclusions: In normal 20.5 day fetal rats, the lungs demonstrate responsivity to maternal hyperoxia with a significant decrease in PA Doppler PI and PEDRF/PSV. This response does not occur in more severe LH with CDH.

OP10.08: Evaluation of the reliability of data acquisition for 3D ultrasound and power Doppler angiography of the whole placenta at 12 and 20 weeks gestation

Objectives: 3D power Doppler angiography (3DPD) is used to quantify the vascularity of an organ. Analysis of a stored dataset can be reliable but few studies have considered the reliability of data acquisition. Our aim was to investigate the intraand interobserver reproducibility of serial acquisition of 3DPD data of the whole placenta from women at 12 and 20 weeks gestation. We hypothesised a high level of agreement would exist. Methods: 20 low risk women with an uncomplicated, viable singleton pregnancy were scanned (Voluson 730 Expert) at two gestational age groups: 12+0 to 13+6 and 19+0 to 21+6 weeks. 3DPD whole placental datasets were acquired by two observers: the 1st made two acquisitions and the 2nd a single acquisition resulting in 3 datasets per patient and 120 overall. These were analysed by a single observer who used VOCAL (A plane, 9 degree steps) to define the VI, FI and VFI. The reliability of these measurements was assessed by intraclass correlation coefficients (ICC + 95% CI) and Bland-Altman plots. The presence of systematic bias within and between observers was also analysed. Results: Mean BMI was 24 (SD 5) in each group. Interobserver ICC was highest for the VI 0.81 (0.59–0.92) and VFI 0.76 (0.48–0.90). ICC for FI showed only moderate correlation at 0.55 (0.18–0.79). Bland Altman plots showed the FI to be the most reliable vascular index however at ±15% (expressed as a % of the mean) and ±17% at 12 weeks and ±9% and ±10% at 20 weeks for intraobserver and interobserver differences respectively. Intraand inter-observer differences were greater for VI at ±40% and ±70% respectively at 20 weeks. There was no bias between datasets. Conclusions: This study demonstrates that 3D can be used to reliably acquire power Doppler data from the whole placenta at 12 and 20 weeks gestation. Previous studies had only addressed the reliability of data analysis. Prospective studies are now required to identify if 3DPD is sensitive enough to identify patients with early-onset placental dysfunction.

OC10.03: MRI assessment of regional fractional moving blood volume within the placenta

R. Deshpande1,2, D. Anblagan4, N. W. Jones1,2, N. Raine-Fenning1, G. Bugg2, P. Mansell3, P. Gowland4, L. Leach3 1School of Clinical Sciences, Division of Human Development, University of Nottingham, Nottingham, United Kingdom; 2Deparment of Obstetrics & Gynecology, Queens Medical Centre, Nottingham, United Kingdom; 3School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom; 4Sir Peter Mansfield MRI Centre, University of Nottingham, Nottingham, United Kingdom

OP16.01: Comparison of placental blood flow in the second trimester between normal and diabetic pregnancy using 3D power Doppler standardised to a local vessel

Objectives: In maternal diabetes the placenta is large with abnormal vascular development and increased villous volume. A prospective, longitudinal observational study of 3D power Doppler vascular indices was performed to investigate differences in-vivo in placental vascularity between women with and without diabetes. Methods: 28 normal women and 20 with pre-gestational diabetes, were recruited. Each subject had 3 scans between 12 and 20 weeks gestation using a Voluson 730 Expert scanner. The VOCAL tool within 4D View (GE Medical Systems) was used to outline the placenta in the A plane using the 9◦ rotation step. To compensate for depth attenuation the 3D vascular indices were standardised against the FI at the centre of a nearby vessel. Results: Subjects were matched for age, BMI and parity. Mean FI.fmbv was 52.07 (±6.0), 50.48 (±5.1) and 53.83 (±4.6) at 12, 16 and 20 weeks respectively. ANOVA demonstrated a significant difference across gestation for the FI.fmbv [F(1.86, 83.82) = 6.37; P = 0.003] and between groups (P = 0.001). There was no difference across gestation or between groups (VI.fmbv, P = 0.29; VFI.fmbv P = 0.48) for the other two standardised 3D vascular indices. The FI.fmbv was significantly higher in subjects with microalbuminuria but not related to retinopathy, hypertension, diabetes type or duration. Conclusions: Standardised placental FI (FI.fmbv) is increased in women with diabetes between 12 and 20 weeks gestation. Structural changes in the large and apparently vascular placenta are therefore accompanied by altered function, with increased signal intensity but not markers of vessel numbers demonstrable in-vivo.