Shear-wave elastography for detection of placenta percreta: a case-controlled study

Abstract

Background

Prenatal diagnosis of placenta percreta (PP) is important to be able to provide effective management and a multidisciplinary approach to minimize the complications.

Purpose

To evaluate the role of shear-wave elastography (SWE) in the prenatal diagnosis of PP.

Material and Methods

A total of 18 women with PP and 20 pregnant women with normal placenta in the second or third trimesters were included in this prospective study. SWE was used to determine the elasticities of the placenta (in the maternal edge of the placenta) and myometrium. The obstetric data regarding grayscale and Doppler ultrasonography, and perinatal outcomes were reviewed. A mean placental SW velocity (SWV) cut-off value was determined to predict the presence of placental adherence.

Results

The SWV values of the PP group in the maternal edge of the placenta were significantly higher than those of the control group (1.95 ± 0.19 m/s and 1.69 ± 0.23 m/s; P = 0.001). Myometrial SWV was also higher in the PP group compared to the control group (2.25 ± 0.39 m/s and 1.90 ± 0.71 m/s; P = 0.002). A receiver operating characteristic (ROC) curve analysis was performed and the best cut-off value of placental SWV was determined as 1.92 m/s with sensitivity of 58% and specificity of 80%, to predict the placental adherence in patients with PP.

Conclusion

Placental stiffness was significantly higher in patients with PP than in pregnant women with normally localized placenta. Thus, we thought that SWE of the placenta might be used as an alternative method in the diagnosis of PP.

Keywords

Placental stiffness placenta percreta shear-wave elastography

Introduction

Morbidly adherent placenta is the spectrum of abnormal implantation of the placenta into the uterine wall. This implantation of the uterus includes three grades according to the difference of invasion depth into the muscular layers of the uterus: placenta accreta, chorionic villi attach to the myometrium; placenta increta, chorionic villi invade into the myometrium; and placenta percreta, chorionic villi invade through the serosa.

Placenta percreta (PP) is a serious complication of pregnancy characterized by placental hyperinvasion, where the villi penetrate the full thickness of the myometrium, which can cause both fetal and maternal morbidity (unplanned surgery, massive bleeding and resultant disseminated intravascular coagulation, adult respiratory distress syndrome, renal insufficiency, etc.) and mortality (1).

Prenatal diagnosis of PP is very important to be able to provide effective management and a multidisciplinary approach to minimize the above-mentioned complications associated with percreta. Grayscale ultrasonography (US) and Doppler US are commonly used imaging modalities for the diagnosis of PP. Pelvic US is highly reliable to diagnose or exclude the presence of placental adhesion disorders (2). In addition, magnetic resonance imaging (MRI) provides a greater soft tissue contrast and a larger field of view when compared with US. Therefore, MRI is accepted as an excellent tool for staging and topographic evaluation of adhesive disorders (3). Although these imaging techniques are useful in the diagnosis of PP, none of them is a definitive diagnostic method (4). The diagnostic accuracies of MRI, US, and color Doppler US in detecting the presence of invasive placentation have been reported as sensitivity and specificity of MRI were both 95%, the sensitivity and specificity of US were 85.7% and 88.6%, respectively, while the sensitivity of color Doppler US was 62.5% with a specificity of 100% (5,6).

Shear-wave elastography (SWE) is a novel ultrasonography technique that is used to obtain information about the elasticity of soft tissues. Although the safety of SWE in the developing fetus has not been fully established because of the high energy of this modality, recent studies showed that SWE has no potential risk (thermal or chemical) to the placenta and fetus (7 –10). Therefore, there has been much recent work on placental elastography in pregnant women with pre-eclampsia, gestational diabetes, preterm delivery, fetal abnormalities, fetal growth restriction, and alloimmunization (11 –16). In addition, this method has shown that abnormal structural changes affect placental stiffness in placenta previa (17). However, it has not been previously used in the study of PP, which is the most dangerous form of adhesive placentation when prenatal diagnosis is missed. In the present study, the application of SWE was used for placental evaluation in patients with PP. The aim of the present study was to determine whether placental elasticity using this method might facilitate the initial diagnosis of PP in the prenatal period.

Material and Methods

This prospective case-controlled study was conducted between June 2015 and May 2017. The study conformed to the principles of the 2008 Declaration of Helsinki and was approved by the Local Ethics Committee (no: 74059997-050.04.04, 2017). Each participant gave written informed consent.

The study included 18 consecutive pregnant women who underwent Cesarean section (CS) for initial diagnosis of PP and 20 pregnant women who had previous CS and preterm labor with no signs of abnormally invasive placentas. Patients with multiple gestation, smoking, taking any medication, fetal anomalies, or systemic diseases including cardiovascular and endocrinological conditions such as gestational diabetes, preeclampsia, HELLP syndrome, and intrauterine growth retardation (IUGR) were not included in the study.

The initial diagnosis of PP was made by ultrasonographic examination (Voluson 730 Expert scanner; GE Healthcare, Milwaukee, WI, USA) that showed an absence or thinning (<1 mm) of myometrial tissue at the placental site. In addition, vascular invasion of the bladder was evaluated during Doppler US. All sonographic examinations were performed by the same obstetrician. MRI was not needed for diagnosis in any of the cases. The control group consisted of pregnant women with anterior placenta. Eight patients had anterolateral placenta and 10 patients had anterior placenta totally; however, no patient had posterior placenta in the study group. After examination of obstetric US (including fetal biometry, amniotic fluid index, and fetal anatomy) and Doppler examination in the Obstetrics and Gynecology Department, all the patients and the control group were transferred to the Radiology Department for evaluation of placental elasticity with SWE.

The procedure of the SWE examination of the placenta was as follows: all elastography examinations were conducted with 9L4 linear transducer using Virtual Touch Tissue Imaging Quantification (VTIQ) option (Siemens ACUSON S3000; Siemens Healthcare). Each participant was in the supine position and the placental and myometrial echogenicity and homogeneity were evaluated by the grayscale US using a linear probe before starting the elastography (Fig. 1). In both groups, elastography measurements were taken from the area 0.5 cm beneath the uterine perimetrium by checking if the region belongs to the placenta or myometrium. In the PP group, this area was consistent with the maternal edge of placenta. In the control group, this area corresponded to the myometrium. In the PP group, the elasticity of the myometrium near the adherent placenta was also determined (Fig. 2a and b). In the control group, the elasticity of the placenta was measured in the maternal edge near the myometrium, in addition to the myometrium (Fig. 2c). All the measurements were taken from homogenous parts of the placental and myometrial tissues avoiding vascular or heterogeneous parts using 1.5 × 1.5 mm² region of interest (ROI). Each patient was instructed to stop breathing, coughing, or any movement during the elasticity measurement. Maximum velocity value was determined as 6.5 m/s for all the examinations. Three velocity measurements were obtained for each of the placental and myometrial regions. The mean of these three measurements was calculated and noted as a final value of shear-wave velocity (SWV; in m/s) for the placenta or myometrium separately in each pregnant woman. The depths from skin surface to ROIs were also noted for each three ROI measurements for tissues and a final value of depth (cm) for placental or myometrial ROIs separately.

Fig. 1.

(a) A pregnant woman with normal placenta. Image of grayscale ultrasound shows placental (P) and myometrial (M) echogenicity. (b) A 32-year-old pregnant woman with placenta percreta. Image of grayscale ultrasound shows that placenta (P) has penetrated uterine serosa and extended to near the bladder (B) wall.

Fig. 2.

A pregnant woman with placenta percreta. (a) SW elastogram shows placenta velocity (Vs) values and depth. (b) SW elastogram shows myometrium velocity (Vs) values and depth. (c) A pregnant woman with normal placenta. SW elastogram shows normal placenta and myometrium with velocity (Vs) values and depth. SW, shear-wave.

The demographic characteristics (i.e. maternal age, gravidity, parity, body mass index [BMI], and gestational age) and a detailed medical and obstetric history were documented for all the participants. The preoperative initial diagnosis of PP was confirmed both during the CS and then in the postoperative histopathological evaluation of hysterectomy materials. An extreme trophoblastic invasion of the myometrium and the serosa by chorionic villi was shown for all patients.

All statistical analyses were performed using Statistical Packages for Social Sciences (SPSS) for Windows, version 20.0 (SPSS, Chicago, IL, USA). All data were expressed as mean ± standard deviation (SD) for normally distributed variables and as median and interquartile range (IQR) for non-normally distributed variables. The distribution of variables was assessed with the Shapiro–Wilk test. Comparisons of normally distributed variables between the groups were performed using the Student’s t-test. For comparisons of non-normally distributed variables, the Mann–Whitney U test was used. Pearson correlation coefficients and Spearman’s correlation test were used to determine correlations for normally distributed data and non-normally distributed data, respectively. A value of P < 0.05 was considered statistically significant.

Results

The demographic and clinical characteristics of the patients are shown in Table 1. No significant difference was determined between the control and PP groups with respect to the maternal age, gravidity, parity, BMI, number of CS, and gestational age at sampling (P > 0.05 for all). The median gestational ages at delivery were 32.21 ± 5.30 years in the PP group and 33.25 ± 3.87 years in the control group. A statistically significantly higher rate of maternal complications was seen in the PP group with bladder injury in two cases (10.5% vs. 0%), blood transfusions in 4 (21.1% vs. 0%), and pelvic abscess in 1 (5.3% vs. 0%) (P < 0.001). There was no maternal mortality in both groups. The mean birth weight of infants of women with PP was similar to those of the women in the control group (2654.2 ± 770.3 g and 2626.5 ± 533.7 g, respectively; P > 0.05). Out of 18 infants in the PP group, 1 (5.3%) had an APGAR score < 4, 7 (36.8%) had a score of 4–7, and 10 (57.9%) had a score > 7. There were 10 infants with an APGAR score of 4–7 and 10 with an APGAR score > 7 in the control group. One neonatal mortality was observed in the PP group due to preterm labor, and no neonatal mortality was seen in the control group.

Table 1.

Demographic and clinical characteristics of the groups.

	Placenta percreta group (n = 18)	Control group (n = 20)	P
Maternal age (years)	34.74 ± 6.00	32.80 ± 4.33	NS
Gravidity (n)	5.74 ± 1.75	4.90 ± 1.44	NS
Parity (n)	3.95 ± 1.43	3.40 ± 1.27	NS
Body mass index (kg/m²)	26.89 ± 2.43	26.85 ± 1.98	NS
Gestational age (weeks)	32.21 ± 5.30	33.25 ± 3.87	NS
Previous Cesarean section (n)	3.05 ± 1.22	2.90 ± 1.02	NS

Values are given as mean ± SD.

NS, not significant (P > 0.05); SD, standard deviation.

The mean SWV of the placenta was 1.95 ± 0.19 m/s for the PP group and 1.69 ± 0.23 m/s for the control group (Fig. 3a). There was a significant difference between the PP group and the control group in terms of placental stiffness (P = 0.001). Myometrial SWV was also higher in the PP group compared to the control group (P = 0.002), with median values of 2.25 ± 0.39 m/s in the PP group and 1.90 ± 0.71 m/s in the control group (Fig. 3b). There was a positive correlation between placental SWVs and myometrial SWVs in the PP group and in the control group in total (P = 0.003, rho = 0.475).

Fig. 3.

(a) Receiver operating characteristic curve analysis for placental SW velocity values in patients with placenta percreta. (b) The diagram of mean SW velocities of myometrium in the groups. SW, shear-wave.

When depths from skin surface to ROIs were examined, the range of ROI depth was 1.00–3.20 cm for myometrial measurements and 1.13–3.93 cm for placental measurements. There was no significant difference between the two groups in terms of myometrial ROI depth from the skin (P = 0.515). However, the placental ROI depths were different in the two groups (P < 0.001). There was a negative correlation between placental SWVs and the depth in both groups totally (P < 0.001, r = –0.696). There was also a negative correlation between myometrial SWVs and the depth in total (P = 0.004, rho = –0.452).

To evaluate the diagnostic performance of SWE on PP for placenta, a receiver operating characteristic (ROC) curve analysis was performed. The area under the ROC curve (AUC) was 0.789 (95% confidence interval [CI] = 0.649–0.930) (Fig. 3a). The best cut-off point for the value of placental SWV was determined as 1.92 m/s (the sensitivity was 58% and the specificity was 80%). The diagnostic performance of SWE on PP for the myometrium in the ROC analysis was AUC 0.726 (95% CI = 0.566–0.887) (Fig. 3b). The value of 2.19 m/s for myometrial SWV had a 68% sensitivity and 60% specificity. When we used a cut-off value of 2.33 m/s for myometrial SWV, sensitivity was 42% and specificity was 90%.

Discussion

PP is the most aggressive form of morbidly adherent placental anomalies in which chorionic villi penetrate the myometrium beyond the uterine serosa. It may lead to life-threatening complications such as massive bleeding, unplanned surgery, and peripartum hysterectomy when not diagnosed in the antenatal period. Fitzpatrick et al. (4) showed that placenta accreta, increta, and percreta could not be definitively diagnosed in the antenatal period of many patients. The imaging methods used in the diagnosis of PP include US and MRI, although there are some pitfalls. US is a user-dependent imaging method and it is therefore not possible to obtain objective data. MRI is an excellent method for the diagnosis of PP with high soft tissue contrast but it is not cost-effective and is not an imaging modality that all patients can easily access. Furthermore, a meta-analysis showed that there was no difference in sensitivity or specificity between US and MRI for the diagnosis of morbidly adherent placenta (7). SWE is a promising technique that is used to measure tissue stiffness in vivo. Placental stiffness in a healthy pregnancy or pregnancies accompanied by various pathologies has been studied in recent years (15,16,18,19). In the present study, the mean SWV was 1.69 ± 0.23 m/s in the control group, which was a higher value than the mean velocity values of previous studies, such as by Ohmaru et al. (20) with a mean value of 0.98 ± 0.21 m/s, and by Wu et al. (19) with a mean value of 0.98 ± 0.26 m/s in healthy pregnancies. These two studies were compatible with each other, as both studies used the same elastography technique and the same ultrasound probe (4C1 convex probe). However, in the present study, the same elastography technique was used with a different probe (9L4 linear probe) that could demonstrate a more superficial area (maternal edge of placenta) with good quality. The depth was found to have an effect on the measured SWV value and there was a negative correlation between them (21). Therefore, the use of the same elastography method with a more superficial location could explain why the values were higher in the present study compared with the two previous studies. Additionally, the gestational age at the measurement (at 14–40 weeks and 17–40 weeks in the studies by Wu et al. and Ohmaru et al., respectively) might contribute to their lower values compared with our results. It has been showed that SWV tended to increase with advanced gestational age due to the placental fibrotic changes that affect tissue elasticity (20). This issue might explain increased SWV of the placenta observed in the control group of the present study.

It is unknown whether the placental positions, such as low-lying, anterior, or posterior locations, may constitute a bias for elastography. Alıcı et al. (17) reported higher placental elasticity values in the placenta previa group than in normal localized placentas. However, they did not find any significant difference between the placenta previa with and without accreta. So, they thought that this increase may be related with placental location. Davie et al. (22) reported that the elastogram was useful in the case of morbidly adherent placentation that was localized in the posterior uterine wall.

It is necessary to mention that there is lack of utility of elastography technique performed with a linear probe (9L4) to diagnose PP when the placenta is predominantly posterior. There have been very few reports in the literature about myometrial stiffness. In the only one, Soliman et al. (23) studied 32 non-pregnant healthy women in terms of myometrial and endometrial stiffness with SWE. The mean SWV of the myometrium was reported to be 2.82 ± 0.77 m/s, which was a very high value compared with the current study result (1.90 ± 0.71 m/s). We hypothesized that the main factor causing this difference was due to the study population in that report being non-pregnant women, and myometrial stiffness might decrease with pregnancy.

The results of the present study showed that the placental stiffness of the maternal edge was significantly higher in patients with PP than in normal pregnancies. Although stiffness was measured only from the maternal edge, studies have shown similar values in any region of the normal placenta indicating that SWE values from any region could be used for the overall stiffness of the placenta (24,25). Increased placental stiffness has been reported in many pathologies such as pre-eclampsia, Rh alloimmunized pregnant women with hydropic fetuses, or pregnancies with fetal anomalies, possibly due to some histopathological changes in the placenta (15,16,25). Sugitani et al. (10) performed histopathological examinations on placentas showing increased SWV values and found widespread infarction and inflammation.

The present study has some limitations. The main limitation was the relatively low number of participants because of the rarity of PP. In addition, we did not investigate the histopathological changes in the placentas with PP, which could have revealed the pathology causing the stiffness. Furthermore, SWV could only be measured from the maternal edge of the placenta as the linear probe could be used only for superficial tissues. Finally, placental elasticity measurements were performed by a single radiologist, so inter-observer variability was not performed for this study.

However, we used a prospective study design, and the characteristics of the participants (age, gravidity, parity, gestational age, and the number of CS) were homogeneous in the study groups. In addition, this is the first study using the SWE method for the prenatal diagnosis of PP in women. These represent some of the strengths of our study. Although we observed the big overlap between the affected cases and the control group in value of placental SWV up to 1.92 m/s, a value greater than 1.92 m/s has a good predictive value for affected cases. The AUC value of 0.789 (95% CI = 0.649–0.930) detected in the ROC analysis indicated that SWE had a good discriminatory power as a diagnostic test for PP. On the basis of our study results, the measurement of placental elasticity might be a useful imaging method in the prenatal diagnosis of PP. However, a larger number of prospective, randomized controlled studies should be performed to clarify the predictive value of placental stiffness for PP.

In conclusion, placental stiffness was significantly higher in the patients with PP than in the pregnancies with normal localized placentas. SWE of the placenta might be used as a novel, non-invasive, and objective method in the prenatal diagnosis of PP to supplement the existing methods.

Footnotes

Acknowledgements

The authors thank Professor Tevfik Sabuncu for his support during the writing of this article.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Dilek Sen Dokumaci

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