Image-guided Bariatric Arterial Embolization (BAE) for the Treatment of Obesity

Over 40% of Americans are obese, with the prevalence of obesity continuing to rise. Obesity negatively affects general health and has been attributed to an increasing incidence of diabetes, heart disease, vascular disease, joint stress, lumbar spine disorders, liver and biliary disease, and various cancers. In the prior granting period, we developed a minimally invasive, image-guided, percutaneous intervention called bariatric arterial embolism (BAE), which was tested in growing swine and translated to a Phase I clinical trial in patients, and was shown to decrease weight gain in growing pigs based on embolic size and target location and safely cause weight loss in people. While surgical approaches have shown better reductions in weight than BAE, they are highly invasive (requiring reconstruction of bowel), have variable success rates, and can have significant complications. Thus, in this renewal application, we seek to refine and develop alternative strategies for minimally invasive BAE and weight reduction. Using a novel microfluidic device to create high-throughput radiopaque embolics and an anti-reflux catheter, we performed BAE in growing swine and demonstrated the effects of BAE on gastric hormones, i.e., ghrelin, gastrin, GLP-1, etc. with smaller embolics being more effective at reducing weight gain. However, smaller embolics are also associated with increased the risk of severe adverse events including gastric perforation. Ghrelin, the primary hunger hormone, which is produced primarily in the gastric fundus, remains a major target for weight reduction. As BAE would be performed in otherwise healthy patients, the risk of non- target embolization (NTE) to organs that share the same vascular supply as the stomach, such as the liver, spleen, pancreas, remains a concern as well. Thus, critical issues such as improved targeting, safety, and long- term efficacy need to be further addressed in order to translate this procedure from animals into patients as a durable treatment for obesity. In this proposal, we seek to improve the safety of BAE using radiolabeled embolics as well as test two new concepts for minimally invasive, image-guided weight loss. We will test these techniques in obese dogs rather than growing pigs as a more realistic model of obesity in people. Our Specific Aims include: 1) Evaluate the safety and efficacy of Yttrium-90 labeled embolics for BAE; 2) Evaluate microencapsulated, iron-oxide nanoparticle (MIONPs) combined with magnetic hyperthermia (MHT) for weight loss; and 3) Develop MR-guided vagal cryoablation as a weight-loss strategy to determine long-term minimally invasive techniques for treating obesity.