Interpretation
Early onset preeclampsia and placenta-related FGR are associated with incomplete transformation of the spiral arteries, which result in hypoperfusion of the placenta and induced placental infarction5, 6. SMI is good for visualizing minute blood flow; therefore, it can easily help identify lesions of placental infarction as lack of vascularity surrounding normal placental blood flow. In contrast, in tissues with avascular villi, only capillaries are absent in the villous tissue 7, which is not distinguishable from normal placenta using B-mode ultrasound. Even with conventional color Doppler, it is difficult to visualize the minute blood flow of the capillaries in the terminal villi. If the flow velocity range is lowered to detect such minute flow, motion artifacts would disturb the expression of real blood flow. However, SMI enables the expression of such thin and sharp terminal villous blood vessels. Therefore, ultrasound diagnosis of avascular villi can be established by identifying the presence of slow congested maternal blood flow in the intervillous space with absent peripheral villous blood vessels. We believe that this is a breakthrough outcome of the current study.
Maternal vascular malperfusion, such as pre-eclampsia and FGR, cause utero-placental hypoxic disorder due to incomplete remodeling of the spiral arteries in the first trimester, thus, resulting in placental infarction 8. Isolated small infarcts can be found pathologically in uncomplicated pregnancies; however, multiple central infarcts often associated with intervillous fibrin deposition are found in severe preeclampsia and FGR 7. Although conventional ultrasound can detect these large lesions as complex echogenic intra-placental masses close to the basal plate9, SMI enables the detection of these small lesions even in tertiary villous tissues. However, the diagnostic accuracy for predicting infarction and avascular villi using SMI was higher in cases with FGR than that in cases with pre-eclampsia. Cases more adversely affected by maternal malperfusion, such as those with FGR and preeclampsia, are likely to have many and/or large pathologic findings in the placenta, which we believe might be the reason that much larger lesions could be easily detected. Diffuse small infarctions might be difficult to distinguish from avascular villi expressed as scatter without villous trees (Figure 5, Appendix S6) .
Contrary to maternal vascular malperfusion, occlusion or compression of the umbilical cord, such as hyper-coiled cord, can cause a dilation of stem villi 7. Consequently, fetal vascular malperfusion, which is characterized by thrombosis and ischemic villi due to umbilical cord blood flow stasis result in FGR10. Therefore, in cases of FGR, we hypothesized that various placental causes of FGR, both maternal and fetal vascular malperfusion, could be distinguished using SMI. We focused on the dilatation of stem villi as one of the findings of fetal vascular malperfusion; however, the accuracy of ultrasound diagnosis was low. Since SMI is an ultrasound Doppler method, SMI blood flow image can be easily enhanced. Furthermore, in histological evaluation, the slice of the tissue does not always include the cross section of the blood vessel in the center. Therefore, we believe the discrepancy between the ultrasound findings and sliced histological findings to be large. The findings of congestion in stem villi are relatively large compared to the other findings in the present study. In such a large vascular evaluation, comparison between the B-mode ultrasound and macroscopic placental findings might be superior to the comparison between SMI and histological findings.
Placental histological findings of chorangiosis are often investigated in the placenta in cases of preeclampsia. Chorangiosis is believed to form due to an adaptive response to placental hypoxia11. In the present study, we defined chorangiosis as an ultrasonographic finding when the Doppler strength of SMI was higher than that of the surrounding villi. However, it was difficult to distinguish the exact chorangiosis from normal placental tissue. We believe that this is because of the relative comparison of echogenicity with the standard villous findings. Originally, the diagnosis of chorangiosis should be pathologically made when hyperbranching is confirmed 12. Radically, we noticed that the definition of ultrasound findings of chorangiosis should be reconsidered.