Photoacoustic tomography has great potential to image dynamic functional changes in vivo . Many tomographic systems are built with a circular view geometry, necessitating a linear translation along one axis of the subject to obtain a three-dimensional volume. In this work, we evaluated a prototype spherical view photoacoustic tomographic system which acquires a 3D volume in a single scan, without linear translation. We simultaneously measured relative hemoglobin oxygen saturation in multiple placentas of pregnant mice under oxygen challenge. We also synthesized a folate-conjugated indocyanine green (ICG) contrast agent to image folate kinetics in the placenta. Photoacoustic tomography performed at the wavelength of peak optical absorption of our contrast agent revealed increased ICG signal over time. Through these phantom and in vivo studies, we have demonstrated that the spherical view 3D photoacoustic tomographic system achieves high sensitivity and fast image acquisition, enabling in vivo experiments to assess physiological and molecular dynamics.

The placenta performs many physiological functions critical for development. Insufficient placental perfusion, due to improper vascular remodelling, has been linked to many pregnancy-related diseases. To study longitudinal in vivo placental perfusion, we have implemented a pixel-wise time–intensity curve (TIC) analysis of contrast-enhanced ultrasound (CEUS) images. CEUS images were acquired of pregnant Sprague Dawley rats after bolus injections of gas-filled microbubble contrast agents. Conventionally, perfusion can be quantified using a TIC of contrast enhancement in an averaged region of interest. However, the placenta has a complex structure and flow profile, which is insufficiently described using the conventional technique. In this work, we apply curve fitting in each pixel of the CEUS image series in order to quantify haemodynamic parameters in the placenta and surrounding tissue. The methods quantified an increase in mean placental blood volume and relative blood flow from gestational day (GD) 14 to GD18, while the mean transit time of the microbubbles decreased, demonstrating an overall rise in placental perfusion during gestation. The variance of all three parameters increased during gestation, showing that regional differences in perfusion are observable using the pixel-wise TIC approach. Additionally, the high-resolution parametric images show distinct regions of high blood flow developing during late gestation. The developed methods could be applied to assess placental vascular remodelling during the treatment of the pathologies of pregnancy.

Functional photoacoustic imaging of the placenta could provide an innovative tool to diagnose preeclampsia, monitor fetal growth restriction, and determine the developmental impacts of gestational diabetes. However, transabdominal photoacoustic imaging is limited in imaging depth due to the tissue’s scattering and absorption of light. The aim of this paper was to investigate the impact of geometry and wavelength on transabdominal light delivery. Our methods included the development of a multilayer model of the abdominal tissue and simulation of the light propagation using Monte Carlo methods. A bifurcated light source with varying incident angle of light, distance between light beams, and beam area was simulated to analyze the effect of light delivery geometry on the fluence distribution at depth. The impact of wavelength and the effects of variable thicknesses of adipose tissue and muscle were also studied. Our results showed that the beam area plays a major role in improving the delivery of light to deep tissue, in comparison to light incidence angle or distance between the bifurcated fibers. Longer wavelengths, with incident fluence at the maximum permissible exposure limit, also increases fluence within deeper tissue. We validated our simulations using a commercially available light delivery system and ex vivo human placental tissue. Additionally, we compared our optimized light delivery to a commercially available light delivery system, and conclude that our optimized geometry could improve imaging depth more than 1.6×, bringing the imaging depth to within the needed range for transabdominal imaging of the human placenta.

No abstract

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.