(676d) Imaging Echogenic Microparticles in the Gastrointestinal Tract: Demonstration of a New Class of Ultrasound Contrast Agents for Noninvasive Diagnosis of Eosinophil Esophagitis

Imaging the transport of microparticles in GI tract is important to using them as ultrasound contrast agents.  This is particularly critical in the esophagus where peristalsis driven flow (2-4 cm/s) drags contrast agents through the 20-35 cm long adult esophagus in 5-20 s, yet image contrast agents are essential to understand the spatial distribution of molecular markers of esophageal diseases. For example, eosinophilic esophagitis (EoE) is characterized by patchy invasion by eosinophils, inflammatory leukocytes not found in the healthy esophagus.  At the molecular level, eosinophils release granule proteins, such as the cytotoxic major basic protein (MBP-1), upon activation.  State-of-the-art diagnosis of EoE necessitates endoscopy with biopsy that is invasive, and biopsy specimens characterize less than 2% of the esophagus even though the inflammation is patchy, suggesting the need for numerous biopsies to ensure that the involved area has been adequately sampled. 

Here we report a new ecogenic contrast agent comprised of insulin particles approximately 0.1-3.0 mm in diameter that can be used as ultrasound contrast enhancement agents labeled with eosinophil specific antibodies to facilitate the diagnosis of EoE.  We prepared the first eosinophil specific ultrasound contrast agents from insulin particles, tethering EoE specific antibodies to their surfaces, and experimentally modeled the transport and binding of these agents to eosinophil proteins on ex vivo monkey esophagi. The results show that insulin particles can be observed by ultrasound and bind to the granule proteins.  From serial ultrasound images, we determine the characteristics and concentration profile of the particle slurry in the esophagi, track changes in the binding layer thickness over time, and evaluated surface binding kinetics.  Our results show that insulin particles provide strong ultrasound contrast and bind to the granule proteins even at air-water interfaces that are challenging for other classes of agent.  These results indicate the potential of this new class of contrast agents to diagnose a broad range of lung and gastrointestinal diseases.