3D microvasculature: volume and network quantification
Terminal villous shapes are influenced by vascular development and abnormal vascular development is linked to PE10. A vascular casting study demonstrated a reduction of total vasculature in severe PE54. Moreover, higher frequency of avascular villi are described in EO-PE compared to term control55, providing a potential explanation for reduced vascular fraction (Figure 4C). Moreover, vessel diameters are hypothesized to be influenced by placental hypoxia10. Therefore, vessel diameter patterns (Figures 4A, 4B) provide an interesting imaging target.
MPM enables investigation of intact 3D microvascular networks and network quantification. Besides branchpoint density and tortuosity (Figures 4D, 4E), network quantification can provide numerous quantitative morphological descriptors (Figure S13). According to current hypotheses (Figure S14), LO-PE exhibits increased branching, i.e., predominant vascular development by branching angiogenesis. Conversely, EO-PE placental development is hypothesised to be characterized by predominance of non-branching angiogenesis10, 56.
During normal development, non-branching angiogenesis is the dominant process of vascular growth later in gestation57. Since (EO-)PE pregnancies in our study group were terminated earlier than control pregnancies (Table S1), younger gestational age is a potential confounding variable. Hence, idiopathic preterm birth placenta, which mainly experienced branching angiogenesis, is a good additional control. Nevertheless, the vascular fraction from the idiopathic preterm control placenta and term placentas did not differ significantly in our preliminary data (Figure 4C). Differences (although non-significant) regarding network properties between term- and preterm placenta (Figures 4C, 4D) can be a result of developmental phases. This does indicate the importance of including age-matched control placenta to study vascular network properties in PE placenta with younger gestational ages.
The tortuous nature of the placental vessels makes them longer, increases their surface area and slows down blood flow to increase the time for diffusional exchange18. High tortuosity (as observed in a IUGR case (Figure 4E) could be an adaptational response for improving diffusion to compensate low villous SA/vol (Figure 3G). However, excessive tortuosity in vessels is also linked to pathological processes, like hypertension or weakened artery wall stiffness58. Vascular twisting would thus be an interesting feature to investigate further regarding placental disease.