In vivo noninvasive systemic myography of acute systemic vasoactivity in female pregnant mice.

Altered vasoactivity is a major characteristic of cardiovascular and oncological diseases, and many therapies are therefore targeted to the vasculature. Therapeutics which are selective for the diseased vasculature are ideal, but whole-body selectivity of a therapeutic is challenging to assess in practice. Vessel myography is used to determine the functional mechanisms and evaluate pharmacological responses of vascularly-targeted therapeutics. However, myography can only be performed on ex vivo sections of individual arteries. We have developed methods for implementation of spherical-view photoacoustic tomography for non-invasive and in vivo myography. Using photoacoustic tomography, we demonstrate the measurement of acute vascular reactivity in the systemic vasculature and the placenta of female pregnant mice in response to two vasodilators. Photoacoustic tomography simultaneously captures the significant acute vasodilation of major arteries and detects selective vasoactivity of the maternal-fetal vasculature. Photoacoustic tomography has the potential to provide invaluable preclinical information on vascular response that cannot be obtained by other established methods.

Towards Transabdominal Functional Photoacoustic Imaging of the Placenta: Improvement in Imaging Depth Through Optimization of Light Delivery.

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.

Spherical-view photoacoustic tomography for monitoring in vivo placental function.

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.

Longitudinal characterization of local perfusion of the rat placenta using contrast-enhanced ultrasound imaging.

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.