A maleimide-based in-vitro model for ultrasound targeted imaging

Intricate variations and poor visual access result in the difficulty in studying the property of adherent targeted bubbles using an in vivo model. Here, we propose a simple in-vitro model based on the natural adhesion of maleimide bubbles to gelatin. We validated the maleimide-mediated bubble adhesion using flat gelatin phantoms. Treating the gelatin surfaces with reducing agent yielded abundant cysteine molecules for attaching maleimide bubbles. An optical microscope and a homemade ultrasound imaging system equipped with a 40-MHz transducer were adopted to observe the acoustic responses of adherent bubbles. Comparing the results of optical observations from experimental and control tests support the bubble adhesion indeed relying on maleimide-cysteine tethering. The intensity of the echoes from a bubble-bound gelatin surface increased with the bubble adhesion density compared with that from a clear gelatin surface. The echo enhancement reached a plateau at 40-42 dB as the bubble adhesion densities were higher than 1.47 × 10(5) bubbles/mm(2). The adherent bubbles would be disrupted rapidly under the exposure of 300-kPa ultrasound pulses. However, increasing the adhesion density to 3.62 × 10(5) bubbles/mm(2) resulted in the echo enhancement being maintained at a duration of 40 min. The advantages of this in-vitro model over previously proposed ones include better stability, less expense, and fewer preparation procedures.