Super-resolution Optoacoustic Imaging of Cerebral Microcirculation with Indocyanine Green Microcapsules

Optoacoustic tracking of small microparticles flowing throughout microvascular networks enables functional microangiography deep into optically opaque biological tissues, essentially breaking through the resolution limits imposed by acoustic diffraction. Localization optoacoustic tomography (LOT) has recently been shown to provide quantitative flow velocity and oxygen saturation readings in deep-located microvessels with a resolution beyond the acoustic diffraction barrier (super-resolution). However, in vivo LOT imaging has been challenged by the strong background absorption of blood and by the biocompatibility of the materials employed. Herein, we achieved in vivo individual detection and continuous tracking of indocyanine green (ICG)-based micrometer-sized capsules using an optoacoustic tomography system at laser energy levels considered safe for human use. In vivo LOT imaging was then enabled with contrast materials consisting of biopolymers and a clinically approved dye, which is poised to facilitate noninvasive deep tissue imaging of microcirculation and pave the way toward an eventual clinical translation of this approach.