The altered placental function which is characteristic of preeclampsia is challenging to characterize with existing imaging techniques. We have developed ultrasound-guided spectral photoacoustic imaging of placental function in an in vivo rat model of preeclampsia, and investigated the impact of therapy on preeclampsia and placental function. Additionally, we have studied the acute vascular response during pregnancy – determining vascular selectivity and response time to vasoactive compounds — using photoacoustic tomography. We integrate our photoacoustic imaging methods with contrast-enhanced ultrasound to provide measures of placental vascular flow. By combining these hybrid optical-acoustic imaging techniques, we characterize placental pathologies and their responses to treatment.
Transabdominal imaging using photoacoustics (PA) is limited by optical attenuation of tissue due to high scattering and absorption in the near infrared (NIR) window. Tissue attenuation is lowered when imaging with longer wavelengths in the NIR window (> 950 nm). However, intrinsic optical contrast is limited in this range and exogenous agents such as gold nanorods (AuNRs) prove popular alternatives. AuNRs have unique optical absorption peaks, due to localized surface plasmon resonance (LSPR), which allow tuning to wavelengths with minimal tissue attenuation. However, AuNRs tend to be bulky (> 50 nm) when adjusting peak LSPR to deep NIR wavelengths leading to poor clearance. In this study, we explored PA signal generation of a biodegradable and biocompatible semiconductor contrast agent – Cu-Fe (bornite) nanocrystals. The semiconductor nature of the nanocrystals allows for particles to be small (3-8 nm) facilitating excretion through kidneys. Here, PA signal generation of bornite was compared to two conventional photoacoustic contrast agents – AuNRs and indocyanine green dye. We found that at similar mass concentrations, bornite generated PA signal 5× greater than AuNRs. In-vivo imaging of bornite showed a 2x increase in sensitivity compared to AuNRs at similar volume concentrations.
Vasoactivity is an important physiological indicator of cardiovascular health which is frequently measured using ex vivo vessels to determine functional mechanisms and evaluate pharmacological responses. Currently, there are no imaging methods available to assess vasoactivity in multiple vascular beds of living animals noninvasively. In this work, we have developed methods to use photoacoustic tomography to assess vasoactivity in vivo in systemic vasculature of living animals. A spherical-view photoacoustic tomography system was used to monitor acute vasodilation in the whole abdomen of a pregnant mouse in response to injection of G-1. After 3D image reconstruction, the diameter of the iliac artery and photoacoustic signal intensity of a placenta over time was measured. The artery and placenta had differential response to the vasodilator G-1. We validated the observed vasodilation of artery by monitoring the change in cross-sectional diameter of an individual artery using standard B-mode ultrasound imaging.
Using spectral photoacoustic imaging (sPAI) to estimate oxygen saturation of tissue at depth suffers from inaccuracies due to the unknown optical absorption and scattering properties of tissue. Because of the high scattering and absorption of light by tissue, the estimation of concentrations of Hb and HbO2 from the measured photoacoustic (PA) signal intensity can be erroneous. Simulation of wavelength-dependent light transport in tissue can help to estimate the local fluence distribution within the tissue. In this work, a Monte Carlo simulation has been implemented to simulate the fluence distribution in placental tissue. We obtained sPAI images of ex vivo human placental tissue and demonstrate improved estimations of hemoglobin oxygen saturation by using a fluence correction derived from the Monte Carlo simulation. The results show that with simulation correction, the oxygen saturation value is 12.61±3% which is closer to the value 6.8% directly measured from ex vivo human placenta using invasive oxygen probe.
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