Multiparametric super-resolution optoacoustic imaging with ICG-tagged microbubbles

Localization optoacoustic tomography (LOT) has recently emerged as an adept imaging approach for super-resolution functional microangiography at depths out of reach for conventional optical microscopy methods. LOT enables simultaneous measurements of microvascular morphology, oxygen saturation, and blood flow velocity via rapid tracking of highly-absorbing microparticulate agents. These distinctive multiparametric imaging capabilities present a remarkable clinical diagnostic potential for a wide spectrum of conditions associated with microcirculatory alterations. However, wider adoption of LOT is impeded by the lack of contrast materials verified for safe intravenous administration in humans. In this work, we developed a new formulation of polyvinyl alcohol (PVA) microbubbles coated in a layer-by-layer fashion with a sufficiently large amount of indocyanine green (ICG) molecules to enable per-particle detection amid the strong background light absorption of blood. LOT imaging of the murine brain could be achieved with no acute toxicity effects observed. Considering that both microbubbles and ICG are routinely administered in clinical ultrasound and fluorescence angiography procedures, it is anticipated that ICG-coated microbubbles will facilitate the clinical translation of LOT.