In Vivo Microscopy of Targeted Vessel Occlusion Employing Acoustic Droplet Vaporization

Abstract

Objective: Embolotherapy is a potential means to treat a variety of cancers. Our approach—gas embolotherapy—introduces the droplets upstream from the tumor and then acoustically activates them to form bubbles for occlusion—a process known as ADV. We wanted to provide the first optical documentation of ADV, lodged bubbles, or vessel occlusion in vivo . Methods: We used the rat cremaster muscle for in vivo microscopy. Perfluorocarbon droplets were administered into the aortic arch. Ultrasound exposures in the cremaster induced vaporization. The cremaster was examined pre‐ and post‐exposure for ADV‐related effects. Two sets of experiments compared the effect of exposure in the capillaries versus the first order arteriole. Results: Bubbles that lodge following capillary exposure are significantly larger (76 μm mean length, 36 μm mean diameter) than those following feeder vessel exposure (25 μm mean length, 11 μm mean diameter). Despite the differing sizes in bubbles, the ratio of bubble length to the hydraulic diameter of all lodged bubbles was 2.11 (±0.65; n = 112), which agrees with theoretical predictions and experimental observations. Conclusions: Our results provide the first optical evidence of targeted vessel occlusion through ADV. These findings could lay the groundwork for the advancement of gas embolotherapy.