Fig. 6. Summary of experiments demonstrating nanobubbles extravasate in diseased islets which increases the contrast signal within the pancreas.

After NBs are delivered, the healthy islet microvasculature are not permeable to NB extravasation so the NBs are retained in the vasculature and cleared. Infiltrated islets in T1D have high vascular permeability and therefore NBs accumulate and are retained in the tissue following infusion, providing a source of sub-harmonic contrast. This sub-harmonic contrast signal therefore provides a diagnostic measure of insulitis and pre-clinical asymptomatic T1D.