All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Institutional Review Board (IRB) approved the observational study of MRI examinations performed for the evaluation of PAS disorders at our institution over the previous 4 years. The IRB granted a waiver of written informed consent since this study used existing MRI data. Funding was provided in the form of the extra diagnostic equipment needed for the study. The funders had no role in the initiation or design of the study, collection of samples, analysis, interpretation of data, writing of the paper, or the submission for publication. The study and researchers were independent of the funders. The authors had control of the data and information submitted for publication. The retrospective study represented a substudy from Magnetic Resonance Imaging in PAS disorders trial. The study was registered at http://www.chictr.org.cn (registration no.ChiCTR2000038604). The full study protocol could be accessed from the corresponding author by request.
The study was conducted at the Radiology Department of a university-affiliated hospital. All patients were evaluated and screened for study eligibility by the author prior to study entry. Of all participants consecutively retrieved from our database spanning from September 2016 through October 2020, only participants with MRI examinations and clinical or histopathological diagnosis of PAS disorders were included. Participants eligible for inclusion were consecutive adults (≥18 years) with suspected PAS disorders, based on the presence of the following: who performed an MRI examination at our institution and for whom clinical or histopathological diagnosis was available. We excluded participants if they had no clinical history and complete images, they were examined by different MRI devices, they received incomplete MRI examinations due to extreme fetal movements resulting in MRI artifacts, or follow-up was not possible.
Standard of reference
The clinical history of PAS disorders is considered as an efficient reference standard to be used in both research and clinical settings, that is, difficult manual, piecemeal removal of the placenta, absence of spontaneous placental separation 20 to 30 minutes after birth despite active management including bimanual massage of the uterus, use of oxytocin and controlled traction of the umbilical cord, retained placental fragment requiring curettage after vaginal birth and heavy bleeding from the placentation site after removal of the placenta during cesarean delivery[19, 20 ]. It has good reliability and validity rates compared with other diagnostic standards, such as histopathology[5, 12, 21, 22].
All MRI examinations were performed on a 1.5 Tesla MRI scanner (Siemens Healthcare, System Type: Avanto, Software Version: Syngo MR B19) with a body array coil that covered the entire pelvis for signal acquisition.Pregnant women were positioned in the supine or left lateral decubitus position in order to comfort and decrease the risk of impaired venous return from caval compression by the uterus. MRI was obtained with a partially filled bladder because an appropriate amount of urine in the urinary bladder aided optimal evaluation of the bladder-serosal interface[22-24].Multi-breathholding was utilized to minimize respiratory motion artifacts[5, 22].
The short MRI protocol (20-25 min) was designed with respect to the safety of pregnant woman and fetus. All participants received T1-gradient sequence for detection of intraplacental hemorrhage and T2-haste sequence to limit artifacts caused by fetal motion. The parameters for T1WI were: repetition time (TR) / echo time (TE), 169/4.76 msec; resolution matrix, 256×173; flip angle (FA), 700; slice thickness, 5mm and for T2WI they were: TR/TE, 1350/94 msec; resolution matrix, 256×205; FA, 1700; slice thickness, 5mm.The field-of-view (FOV) read of 400–480 mm and FOV phase of 75-100% were used. The MRI examinations of some participants also included T2-trufi sequence in the coronal and sagittal planes without fat suppression using TR/TE of 3.87/1.68 msec and FA of 60°; T1-vibe in-phase and out-of-phase sequences in the transversal plane without fat suppression with TR/TE of 7.6/2.4 msec and FA of 10°.To maximize signal, a multi-channel surface coil was used whenever possible. No sedative or gadolinium contrast agent was administered[23, 27].
MRI of PAS disorders was archived to the LandWind Picture Archiving and Communication System (PACS) and then retrieved in Digital Imaging and Communications in Medicine (DICOM) format for image analysis. All images of participants were anonymized. MRI of PAS disorders was independently evaluated by two obstetric fellowship-trained radiologists with 13 and 9 years of experience respectively, who were blinded to all clinical history, including the final histopathological diagnosis.
Texture analysis of PAS disorders was implemented on dark intraplacental bands on T2WI by MaZda software (Version 188.8.131.52; Institute of Electronics, Technical University of Lodz, Lodz, Poland) in BMP format[17, 28, 29]. The flowchart illustrating typical steps of texture analysis was shown in Fig. 1. At first, raw-MRI options consisted of image dimensions with 256×256 and pixels intensity encoded with 8 bits.The ROIs were manually drawn on sagittal and coronal T2WI with MaZda ROI editor by one radiologist and supervised by a board-certified radiologist for consistency. A total of 328 ROIs were positioned, of which 136 on the sagittal plane and 192 on the coronal plane. Four first-order texture parameters were extracted with MaZda options, which were run-length matrix (RLM); co-occurrence matrix (COM); gradient and wavelet. The images were normalized before analysis using the “±3 sigma” technique to minimize the effect of brightness and contrast variation on texture analysis. Parameter selection and reduction was automatically done with Fisher discriminant method in MaZda software.
The two steps of parameter selection and reduction led to a decrease of the parameter space dimensionality in order to those that contributed most to accurate classification of PAS disorders. ROI depiction was repeated twice in a subgroup of 13 participants after a pause of 6 weeks by the same radiologist for intraobserver agreement (intra-class correlation coefficients, ICC=0.90, 95% CI 0.71,0.97) and by another radiologist for interobserver agreement (ICC=0.86, 95% CI 0.61,0.96). Data of the study were blinded for both radiologists. Additionally, two radiologists reviewed texture analysis results to render an impression of the degree of invasion based on the culmination of findings.
Statistical analyses were carried out by NCSS statistical software (PASS, Version 11), IBM SPSS software (SPSS, Version 23) and MEDCALC statistical software (MedCalc, Version 19.5). Data generated or analyzed during the study were available from the corresponding author by request. Normal variables were expressed as mean ± standard deviation, while variables with skewed distribution were expressed as median (interquartile range). A two-tailed P value of less than 0.05 was regarded as indicative of statistical significance. Indeterminate results were considered false-positive or false-negative and incorporated into the final analysis. Missing data were handled by exclusion as well as by the worst-case imputation. The interobserver agreement was tested by the Kappa value(κ=0.78).
The intended sample size was calculated according to power 0.90, alpha 0.05, prevalence of PAS disorders 0.19%, sensitivity 0.78, specificity 0.71 in PASS 11. Analysis of covariance was used by prespecifying gestation age as the covariate when variance homogeneity and parallelism assumption was satisfied for the comparison of data between three groups. Two-step clustering was performed to predict the importance of parameters. Logistic regression models were fitted by carrying out ordinal logistic regression for important parameters. The receiver operating characteristic curves (ROC curve) were derived by calculated sensitivity-specificity pairs for all possible cut-offs. The cut-off of the index test was performed by the maximum Yuden index. The diagnostic accuracy of index test was evaluated from the contingency table.