Lawrence, D. J. | Search bioRxiv

bioRxiv2024

Quantifying Molecular Changes in the Preeclamptic Rat Placenta with Targeted Contrast-Enhanced Ultrasound Imaging

PurposeAbnormal placental remodeling is linked to various pregnancy-related diseases, including preeclampsia (PE). This study applies a bicompartmental (BCM) model to quantify molecular expression changes in the placenta, indicative of abnormal placental remodeling, and evaluates the effectiveness of targeted contrast-enhanced ultrasound (T-CEUS) in detecting the abnormal placental vasculature. The BCM model provides high temporal resolution and differentiation of anatomical artery structures within the placenta by analyzing the distribution of contrast agents. MethodsA targeted contrast agent (TCA) composed of gas-filled microbubbles (MB), with a surface-conjugated peptide to target {nu}{beta}3 integrin, a biomarker for angiogenesis, was used for quantifying placental vascular development. CEUS images were acquired from timed pregnant Sprague Dawley rats with experimentally-induced reduced uterine perfusion pressure (RUPP) placental insufficiency. On gestational day (GD) 18 of a 21-day gestation, CEUS images were acquired from both Normal pregnant (NP; n=6) and RUPP (n=6) dams after injection of the TCA. The BCM model was used to estimate the binding dynamics of the TCA, providing a parametric map of the binding constant (Kb) of the placenta. ResultsThe RUPP group showed a significant reduction in the value of Kb compared to the NP group (p < 0.05). A histogram of the placental Kb was compared to alternative analyses (differential target enhancement, dTE and late enhancement, LE) to demonstrate that it can differentiate between anatomical artery structures with a higher contrast-to-background ratio. ConclusionsThe BCM method differentiates molecular changes associated with the abnormal placental development associated with PE. It also reveals more intricate internal anatomical structures of the placenta in comparison to dTE and LE, suggesting that the BCM could enhance early detection and monitoring of PE.

bioengineering↗

bioRxiv2022

Size-tunable ICG-based contrast agent platform for targeted near-infrared photoacoustic imaging

Near-infrared photoacoustic imaging (NIR-PAI) combines the advantages of optical and ultrasound imaging to provide anatomical and functional information of tissues with high resolution. Although NIR-PAI is promising, its wide application is hindered by the limited availability of NIR contrast agents. J-aggregates (JA) made of indocyanine green dye (ICG) represents an attractive class of biocompatible contrast agents for PAI. Here, we present a facile synthesis method that combines ICG and ICG-azide dyes for producing contrast agent with tunable size down to 230 nm and direct functionalization with targeting moieties. The ICG-JA platform has a detectable PA signal in vitro that is two times stronger than whole blood and high photostability. The targeting ability of ICG-JA was measured in vitro using HeLa cells. The ICG-JA platform was then injected into mice and in vivo NIR-PAI showed enhanced visualization of liver and spleen for 90 minutes post-injection with a contrast-to-noise ratio of 2.42.

bioengineering↗