Targeted contrast enhanced ultrasound imaging to detect molecular changes in the preeclamptic rat placenta

Preeclampsia (PE), affecting 6%–8% of pregnancies worldwide, is characterized by hypertension and proteinuria in late pregnancy stages. The primary cause of PE is insufficient placental vascular remodeling, resulting in placental ischemia. This study analyzes targeted contrast-enhanced ultrasound (T-CEUS) images using a bicompartmental (BCM) model to quantify changes in molecular expression in placentas affected by preeclampsia. T-CEUS employs targeted contrast agents (TCA) to enhance ultrasound signals. To enhance the detection of molecular expression in PE placentas, we modified the surface of targeted TCA microbubbles to bind to ανβ3 integrin, a biomarker associated with angiogenesis. T-CEUS imaging was performed on 12 timed-pregnant Sprague-Dawley rats. On gestational day (GD) 14, 6 rats underwent reduced uterine perfusion pressure (RUPP) surgery to induce PE. On GD 18, CEUS image data was collected following the injection of TCA. The time-intensity curve (TIC) of each pixel was fit to the BCM model to obtain a parameter map of the binding constant (Kb ) within the placenta. RUPP placentas had a lower Kb , compared to normal placentas, which is consistent with the results of two traditional semi-quantitative methods: differential target enhancement (dTE) and late enhancement (LE). Compared to dTE and LE, BCM images can distinguish more intrinsic anatomical structures.