Clinically-translatable High-fidelity Photoacoustic Tomography Enhanced by Virtual Point Sources

Photoacoustic tomography (PAT), a hybrid imaging modality that acoustically detects the optical absorption contrast, is a promising technology for imaging hemodynamic functions in deep tissues. Particularly, PAT is capable of measuring the blood oxygenation level using hemoglobin as the endogenous contrast. However, the most clinically compatible PAT configuration usually employs a linear ultrasound transducer array and often suffers from the poor image fidelity, mostly due to the limited detection view of the transducer array. PAT can be improved by employing highly-absorbing contrast agents such as droplets and nanoparticles, which, however, have low clinical translation potential due to safety concerns and regulatory hurdles. Moreover, unlike hemoglobin, these exogenous contrast agents cannot report the functional hemodynamic information. In this work, we have developed a new methodology that can improve PAT’s image fidelity without hampering its functional capability or clinical translation potential. By using clinically-approved microbubbles as virtual point sources that strongly scatter the local pressure waves generated by surrounding hemoglobin, we can overcome the limited-detection-view problem and achieve high-fidelity functional PAT in deep tissues, a technology referred to as virtual-point-source PAT (VPS-PAT). We have thoroughly investigated the working principle of VPS-PAT by numerical simulations and phantom validations, showing the acoustic origin of signal enhancement and the superiority over traditional PAT. We have also demonstrated proof-of-concept applications of functional VPT-PAT for in vivo small-animal studies with physiological challenges. We expect that VPS-PAT can find broad applications in biomedical research and accelerated translation to clinical impact.

In Vivo Imaging of Mammalian Embryos By NIR-I Photoacoustic Tomography and NIR-II Optical Coherence Tomography Using Gold Nanostars as Multifunctional Contrast Agents

Background High resolution, strong contrast and multimodality visualization of live mammalian embryo is an important requirement for studying foetal development. Photoacoustic Tomography (PAT) and Optical Coherence Tomography (OCT) are two advanced imaging modalities that has been utilized for embryonic imaging. However, high contrast, multiscale and deep tissue visualization of live embryos remains challenging. Results Here, we demonstrate the use of gold nanostars (GNS) as multimodality contrast agents for the visualization and differentiation of embryos in vivo using NIR-I PAT and NIR-II OCT. We perform NIR-I PAT imaging to confirm in vivo GNS accumulation in the foetuses, and then use a customized NIR-II OCT system to further reveal deep, contrast-enhanced micro features of freshly harvested embryos. We investigate two different GNS administration pathways, i.e. intravenous and intravaginal injection, and significant enhancement of signal, image contrast, and imaging depth are achieved for both PAT and OCT. Conclusions These findings prove that PAT-OCT bi-modal imaging with GNS enhancement provides more accurate structural characteristic of live mammalian embryos, and thus reveal its potential for embryonic development visualization and early abnormality examination. These findings prove that PAT-OCT bi-modal imaging with GNS enhancement provides more accurate structural characteristic of live mammalian embryos, and thus reveal its potential for embryonic development visualization and early abnormality examination.