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Discriminative imaging of maternal and fetal blood flow within the placenta using ultrafast ultrasound.

ABSTRACT: Being able to map accurately placental blood flow in clinics could have major implications in the diagnosis and follow-up of pregnancy complications such as intrauterine growth restriction (IUGR). Moreover, the impact of such an imaging modality for a better diagnosis of placental dysfunction would require to solve the unsolved problem of discriminating the strongly intricated maternal and fetal vascular networks. However, no current imaging modality allows both to achieve sufficient sensitivity and selectivity to tell these entangled flows apart. Although ultrasound imaging would be the clinical modality of choice for such a problem, conventional Doppler echography both lacks of sensibility to detect and map the placenta microvascularization and a concept to discriminate both entangled flows. In this work, we propose to use an ultrafast Doppler imaging approach both to map with an enhanced sensitivity the small vessels of the placenta (~100 μm) and to assess the variation of the Doppler frequency simultaneously in all pixels of the image within a cardiac cycle. This approach is evaluated in vivo in the placenta of pregnant rabbits: By studying the local flow pulsatility pixel per pixel, it becomes possible to separate maternal and fetal blood in 2D from their pulsatile behavior. Significance Statement: The in vivo ability to image and discriminate maternal and fetal blood flow within the placenta is an unsolved problem which could improve the diagnosis of pregnancy complications such as intrauterine growth restriction or preeclampsia. To date, no imaging modality has both sufficient sensitivity and selectivity to discriminate these intimately entangled flows. We demonstrate that Ultrafast Doppler ultrasound method with a frame rate 100x faster than conventional imaging solves this issue. It permits the mapping of small vessels of the placenta (~100 μm) in 2D with an enhanced sensitivity. By assessing pixel-per-pixel pulsatility within single cardiac cycles, it achieves maternal and fetal blood flow discrimination.

SUBMITTER: Osmanski BF

PROVIDER: S-EPMC4570988 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionDuring the third trimester of development, the human fetus accumulates fat, an important energy reservoir during the early postnatal period. The fetal liver, perfused by the nutrient-rich and well-oxygenated blood coming directly from the placenta, is assumed to play a central role in these processes. Earlier studies have linked fetal liver blood flow with maternal nutritional status and response to the maternal oral glucose tolerance test. Our aim was to explore the effect of a regular maternal meal on fetal liver blood flow at two timepoints during the third trimester, representing the start and towards the end of the fetal fat accretion period. We also sought to explore the influence of prepregancy body mass index on how the maternal meal affects fetal liver blood flow.MethodsUsing ultrasound Doppler, we examined 108 healthy women with singleton pregnancies in gestational weeks 30 and 36. At each visit, the first examination was performed with the participant in a fasting state at 08.30 a.m., followed by a standard breakfast meal of approximately 400 kcal. The examination was repeated after 105 minutes. Umbilical vein and ductus venosus blood flow was estimated from diameter and blood flow velocity measurements. Fetal liver flow was calculated as umbilical vein flow minus ductus venosus flow, and change in liver blood flow as flow after minus before the meal. The total group was divided into a normal-weight group (prepregancy body mass index 18.5-25.0 kg/m2; n = 83) and an overweight group (prepregancy body mass index >25.0 kg/m2; n = 21). Four women with prepregancy body mass index <18.5 kg/m2 were excluded from these analyses. Non-parametric statistical hypothesis tests were used for group comparisons.ResultsFor the total group, we observed a significant increase in median (10th - 90th percentile) liver flow 28.9 (‒67.9-111.6) ml/min (p = 0.002) following the meal in week 36, but not in week 30, ‒2.63 (‒53.2-65.0) ml/min (p = 0.91). This result in turn yielded a statistically significant increase in delta liver flow from weeks 30 to 36 of 26.0 (‒107.1-146.6) ml/min (p = 0.008). The increase in postprandial liver flow was observed only in the normal-weight group in week 36. Accordingly, the delta liver flow values between the two weight groups were significantly different in week 36 (p = 0.006) but not in week 30 (p = 0.155). Among the normal-weight women, the increase in delta liver blood flow from weeks 30 to 36 was 39.3 (‒83.0-156.1) ml/min (p<0.001); in contrast, we observed no statistically significant change in the overweight group (‒44.5 (‒229.0-123.2) ml/min; p = 0.073). As a substitute for liver size, we divided the delta liver flow values by abdominal circumference and found no changes in the statistical significance results within or between the two weight groups.ConclusionIn our healthy study population, we observed a statistically significant difference in liver blood flow after maternal intake of a regular meal. This effect depended on gestational age and maternal prepregancy body mass index, but apparently was independent of liver size, based on abdominal circumference as a proxy measure.

Project description:BACKGROUND:Placental mRNA was detected in maternal whole blood, raising the possibility of using maternal blood for noninvasive prenatal diagnosis. We investigated fetal mRNA detection in maternal whole blood and determined if it offered advantages over maternal plasma analysis. METHODOLOGY:The concentrations of placental expressed genes, CSH1, KISS1, PLAC4 and PLAC1 in plasma and whole blood from healthy pregnant and non-pregnant individuals were compared by real-time quantitative reverse-transcriptase polymerase chain reaction analysis. Their fetal specificity was investigated by comparing the transcript concentrations in pre- and post-delivery samples and through SNP genotyping by matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry. The gene expression profiles of pregnant and non-pregnant whole blood were investigated by microarray analysis. Upregulated genes in pregnant whole blood were selected for further quantitative analysis. PRINCIPAL FINDINGS:The concentrations of the four transcripts were significantly higher in third trimester maternal whole blood than corresponding plasma without significant correlations. KISS1, PLAC4 and PLAC1 were detected in non-pregnant whole blood but not plasma. The transcripts remained detectable in some postpartum whole blood samples. The PLAC4 mRNA in maternal plasma showed fetal genotype while that in corresponding whole blood indicated both fetal and maternal contributions. Microarray analysis revealed upregulation of genes involved in neutrophil functions in pregnant whole blood including DEFA4, CEACAM8, OLFM4, ORM1, MMP8 and MPO. Though possibly pregnancy-related, they were not pregnancy-specific as suggested by the lack of post-delivery reduction in concentrations. CONCLUSIONS:Maternal plasma is preferred over maternal whole blood for placenta-derived fetal RNA detection. Most studied 'placental' mRNA molecules in maternal whole blood were of maternal origin and might be derived from processes such as 'illegitimate transcription'.

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Discriminative imaging of maternal and fetal blood flow within the placenta using ultrafast ultrasound.

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