Applying ultrasound phase-change contrast agents to guide therapeutic intervention in type 1 diabetes

Abstract

Ultrasound is a widely deployable and cost-effective clinical imaging modality. However, conventional microbubble contrast agents are restricted to the vasculature. Sub-micron nanodroplet (ND) phase-change agents can be vaporized into micron-sized bubbles, serving as a microbubble precursor. In principle, the enhanced permeabiltiy and retention effect can be used with sub-micron NDs to detect injured tissues. Methods to detect type1 diabetes (T1D) progression prior to clinical diagnosis are needed. T1D results from autoreactive T-cells infiltrating the islets of Langerhans, destroying insulin-producing beta-cells. Overt disease takes years to present and at diagnosis there is substantial beta-cells loss. Therapeutic intervention to preserve beta-cell mass is hampered by an inability to follow pre-symptomatic T1D progression and tracking whether therapeutic interventions are impacting disease progression. We will present ultrasound imaging of phase-change nanodroplet (ND) contrast-agent accumulation within the islet. ND accumulation is dependent on immune infiltration, therefore tracks pre-symptomatic T1D development and progression to diabetes. Measurement of ND accumulation detected pre-symptomatic T1D earlier and with greater sensitivity compared to existing measurements of circulating autoantibodies. This provides an opportunity to guide early therapeutic treatments to prevent T1D.